dataesr/scientific-paragraphs-categorization huggingface dataset:
Human nutrition Oil is the most important cottonseed-derived product used for human consumption. In Europe, the consumption of cottonseed oil as such is relatively limited as reflected by the lack of consumption data reported in the EFSA Comprehensive Food Consumption Database (EFSA, 2011). However, cottonseed oil can also be used as an ingredient in the production of a wide variety of food products such as dressings, mayonnaise, fine bakery wares, chocolate spreads and chips. Dihydrosterculic acid (cyclopropaneoctanoic acid, 8-(2-octylcyclopropyl)octanoic acid) is one of a group of cyclopropane fatty acids (CPA) that together with cyclopropene fatty acids (CPE) occur infrequently in most plants. Dihydrosterculic acid makes up 0. 2-0. 4% of total fatty acids in cottonseed  (Xiao-Hong et al.
Overall conclusions The GMO Panel was asked to carry out a scientific assessment of cotton GHB614 9 LLCotton25 9 MON 15985 for import, processing, and food and feed uses in accordance with Regulation (EC) No 1829/2003. No new data on the single cotton events GHB614, LLCotton25 and MON 15985 that would lead to a modification of the original conclusions on their safety were identified. Based on the molecular, agronomic/phenotypic and compositional characteristics, the combination of cotton events GHB614, LLCotton25 and MON 15985 in the three-event stack cotton did not give rise to issues regarding food and feed safety. The newly expressed proteins in the three-event stack cotton did not raise concerns for human and animal health. Food and feed from cotton GHB614 9 LLCotton25 9 MON 15985 are expected to have the same nutritional impact as those derived from the non-GM comparator.
Statistical Analysis The bacterial taxonomic classification data were normalized and standardized. The FROGS package, and VEGAN module of R (Community Ecology Package  [34] ;) were used to generate relative abundance of intestinal microbiota and the diversity indexes from clusters (Chao1, Shannon, Simpson, inverse Simpson). The R software (R 3. 1. 3, R Development Core Team, 2015) was used to analyze all data in this study with a two-way ANOVA model, with, either hindgut or midgut as digestive content (A) and the line effect (TG) as fixed factors and the interaction between digestive and line effects (A x TG). Differences were declared significant at P ≤ 0. 05. Data were reported as mean values with standard error.
ACKNOWLEDGEMENTS We thank the " Université de Pau et Pays de l'Adour "(UPPA)  and "the  Conseil Départemental des Landes"  for the financial support in this project. We thank  Anne Surget  and  Alexandre Hermann  for technical assistance and the staff ( P Maunas  and  N Turonnet ) of the INRA experimental fish farm at  Lees-Athas  for rearing fish.
Selection and expression of potential GGR candidates The Interpro database (EMBL-EBI) predicts over 8000 proteins present within the GGR family (InterPro code: IPR011777), with many homologous genes containing sequence identities as low as 20-30%. After sequence alignment, a phylogeny tree includes 1787 sequences of predicted GGR from the InterPro database. A few GGRs within this database have been confirmed by other groups to reduce a wide variety of large prenylated substrates, including GGPP, DGGGP, geranylgeranylchlorophyll, menaquinone, and dolichol  [25] [26] [27] [28] [29] [30] [31] [32]. To investigate the in vitro prenyl reductase potential of other genes within the GGR family, we selected some with conserved sequence homologies to known GGRs and other more distant sequences. As observed in Fig.
1 , it was possible to observe some subgroups with conserved sequences (e. g. , Mc, Sa, Pf or Hl, Hv1, Hs). Most of the sequences in the predicted GGR family, however, are very divergent. Our selection was then based on kingdom and diversity of species (e. g. , archaea, algae, plant, cyanobacteria, and bacteria), on environmental diversity (e. g. , temperatures, pH, aerobic or anaerobic), as well as particular Fig. 1  Phylogenetic tree representing the diversity of the GGR family of enzymes. The tree includes 1787 sequences of predicted GGRs from the InterPro database. Putative GGRs were selected from various organisms encompassing archaea (red), bacteria (purple), cyanobacteria (blue), alga (cyan), and plants (green). Black circles represent GGRs selected to test for isoprenoid reductase activity within this study; orange circles represent soluble proteins successfully purified and tested for reductase activity.
The H 2 -GGOH and H 4 -GGOH peaks have respective prevalent ion abundances at 261 and 263 m/z, which can be achieved by loss of a 31 Da [M-CH 2 OH] fragment during ionization and subsequent formation of a resonance-stabilized singly or doubly reduced geranylgeranyl fragment. Such fragments most likely originate from the prenyl units distal from the alcohol group being reduced first, in accordance with previous mechanistic proposals performed using various substrates on a variety of GGRs  [29, 32, 33]. Moreover, the H 6 -GGOH peak matches with a phytol peak from the NIST database with > 90% probability, further reinforcing a mechanism of serial reduction of substrate beginning with the δ-prenyl group. Interestingly, several GGRs exhibit unknown side-products, with the most prevalent behavior observed between the H 2 -GGOH and H 4 -GGOH peaks in Pyrolobus fumarii GGR (RT = 8.
0 min) (Fig. 3 ). This peak contains aberrant patterns for prenyl units within m/z window of 50-100, and we suggest these are H 4 -GGOH regioisomers in which one or both internal prenyl units are reduced first, which was suggested from the NIST database with > 80% probability (Additional file 1: Figure  S3 ). Of most noteworthy interest is the product eluted at 7. 5 ± 0. 1 min RT from assays containing GGRs from Sulfolobus acidocaldarius (Fig. 3 ). The mass spectra are matched against the 3,7,11,15-teramethylhexadecan-1-ol compound, a complete hydrogenation product of GGOH, in the NIST database with > 88% probability. SaGGR, among others, has been demonstrated to reduce 3 out of 4 prenyl units of GGPP at best as observed in this work and others  [29, 33]. Because a complete reduction is not observed in isoprenoid pyrophosphate substrates (Fig.
4 ). No fully reduced farnesol peaks were observed under standard assay conditions nor at enzyme concentrations as high as 150 µM at pH 7. 4. However, SaGGR generated a modest amount of H 6 -FOH when incubated under the enzyme's optimal conditions at 50 °C and pH 5. 5  [33]  (Additional file 1: Figure  S4 ). Compared to GGOH, emergent side products are less prevalent in the farnesol TICs. Whereas multiple peaks were observed between the singly and doubly reduced GGOH (Fig. 3 ), a single prevalent peak at 7. 8 min elutes between FOH and H 2 -FOH, mainly observed when incubated in the presence of Pf and MiGGR (Fig. 6 ). The associated mass spectrum is tentatively assigned to a regioisomer of H 2 -FOH where the middle prenyl unit is reduced first (Additional file 1: Figure  S5 ). The spectrum matches the NIST database for (E)-3,7,11-trimethyldodeca-2,10-dien-1-ol with a probability of 85% (Additional file 1: Figure  S5 ).
Sequence analysis and GGR homology Multiple sequence alignments for potential GGR hits were generated using MUSCLE v. 3. 8. 31 and visualized using Geneious 7. 0. 6  [41, 42]. Sequences were curated manually, and phylogeny trees were computed using the maximum likelihood tree within the RAxML Software package, v. 8. 1. 24 under the LG plus gamma model of evolution (PROTGAMMALG in the RAxML model section)  [43]. The MRE-based bootstrapping criterion was automatically determined for phylogeny tree construction. Annotation of the tree was performed in Itol  [44]. After verification of GGR activity, the active enzymes underwent a second multiple sequence alignment and modeled for their predicted protein structures via SWISS-MODEL-PDB using either SaGGR or TaGGR as templates  [45]. Active site geometries and local structures for all proteins were visualized using Chimera  [46].
9  (Left) overlaid prediction of modeled protein structures of proteins (Sa, cyan; Pf, tan; Af, fuschia; Mi, green; Tn, red; Ta, gray; Sc, magenta; Ma, orange) with demonstrated GGR activity using SaGGR (PDB: 4opd) as a template. (Middle) overlaid alignment of protein active sites of residues within 10 Å of either the FAD isoalloxazine ring or GGPP substrate. The conservation of the active site cysteine found in all GGRs (cf. Fig. 8 ) are found in proper position to modulate the redox properties of the cofactor. (Right) examination of the ScGGR active site containing the divergent REG catalytic motif relative to the GGG motif found in archaeal GGRs. Arg293 and Glu294 of ScGGR make critical intradomain hydrogen bonding interactions to accommodate the GGPP binding site E. coli BL21 cells harboring the pG-KJE8 plasmid encoding DnaK, DnaJ, GrpE, GroES, and GroEL protein chaperones (Takara Bio Inc.
A sample injection volume of 2 µL was used throughout  [33]. The HPLC system was coupled to an Agilent Technologies 6210 time-of-flight mass spectrometer (LC-TOF-MS) by a 1/3 post-column split. Contact between both instrument set-ups was established using a LAN card to trigger the MS into operation upon the initiation of a run cycle from the MassHunter workstation (Agilent Technologies). Electrospray ionization (ESI) was conducted in the negative ion mode and a capillary voltage of -3500 V was utilized. MS experiments were carried out in full scan mode, at 0. 86 spectra/second for the detection of [M-H] -ions. The instrument was tuned for a range of 50-1700 m/z. Prior to LC-TOF-MS analysis, the TOF-MS was calibrated via an ESI-L low concentration tuning mix (Agilent Technologies). Data acquisition and processing were performed by the Agilent Technologies MassHunter software package.
Funding This work was part of the  DOE Joint BioEnergy Institute  (https ://www. jbei. org)supported by the  US Department of Energy, Office of Science, Office of Biological and Environmental Research , through contract  DE-AC02-05CH11231  between  Lawrence Berkeley National Laboratory  and the  US Department of Energy. This work, funded by  Total , was performed as part of a collaborative program between JBEI and Total.
data analysis We analysed associations of mortality from the selected cancers with indicators of exposure to styrene using the ungrouped form of Poisson regression, equivalent to the discrete-time hazard model 24 25 to estimate adjusted rate ratios (RRs) and likelihood-based 95% CIs. Follow-up time was treated as the time axis, with each observation representing one person-year of experience or a fraction thereof in the case of censoring during the year. For each type of cancer, we first evaluated demographic and occupational predictors including age at risk, calendar time, sex, country, length of follow-up and time since first exposure. to develop a base model that best fit the mortality data as assessed by the Akaike information criterion (AIC.
Acknowledgments This work was supported in part by grants to BFP from the  Agence Nationale pour la Recherche  ( ANR-13-JSV3-0002-01 ) and the  European Research Council  ( ERC-2013-CoG_616986 ). We thank  Pablo Palazon-Riquelme ,  Danish Patoli , and  Amaury Rey  for comments on the manuscript.
RNA Isolation and Gene Expression Analyses. Colon samples were frozen in liquid nitrogen and stored at -80 °C before RNA preparation. Total RNA was isolated from rat colon specimens using a commercial RNA purification kit (SV total RNA isolation kit, Promega, Madison, WI) and mRNA expression of Muc2 (primer sequences F: CCTTGC TCTGCCATACCCGT, R: ACACTGGTCCTCTCCTCCCT) and TFF-3 (F: TAACCCTGCTGCTGGTCCTG, R: GTTT GAAGCACCAGGGCACA), and the internal control (GAPDH) was measured by qRT-PCR. Furthermore, gene expressions in Toll-like receptor signaling pathway were determined by real-time PCR array according to the manufacturer's protocol (PAMM-0018ZD, SA Biosciences, Frederick, MD) on CFX96 thermocycler (Bio-Rad, Hercules, CA). Data   (P < 0 01) at day 2 but there is no difference among colitic groups (Figure  1 (b)).
Chemicals and instrumentation For each unit, PHMB was quantified and BPs detected using a stability-indicating method adapted from Ku ¨sters et al. (  2013 ), by liquid chromatography (LC) using AS-2055 Plus sampler with LG-1580-02 pump, Jasco MD-2018 plus with diode array detector in ultraviolet-visible range (DAD UV-Vis) and ChromNAV Ò software integrator (Jasco, Evry, France). The LC separation column used was an Agilent Zorbax Eclipse XDB-CN column (4. 6 Â 75 mm) with particle size of 3. 5 mm and guard column (4. 6 Â 12. 5 mm). The mobile phase was an acetonitrile/water mixture (3/97% v/v) in which the acetonitrile was HPLC quality (Chromasolv Ò for HPLC; Honeywell Ò , Roissy CDG, France) and the water was deionized and sterile (Versylene Ò ; Fresenius Kabi France, Louviers, France). The flow rate through the column for the analysis was set at 1.
Data analysis-acceptability criteria The stability of diluted PHMB solutions was assessed using the following parameters: visual aspect of the solution, PHMB concentration, presence or absence of BPs, pH and osmolality. The   (2013). A variation of concentration outside the 90-110% range of initial concentration (including the limits of a 95% confidence interval of the measures) was considered as being a sign of instability. Presence of BPs and the variation of the physicochemical parameters were also considered a sign of PHMB instability. The observed solutions must be limpid, of unchanged colour, and clear of visible signs of haziness or precipitation. Since there are no standards that define acceptable pH or osmolality variation, pH measures were considered to be acceptable if they did not vary by more than one pH unit from initial value (French Society of Clinical Pharmacy (SFPC) & Evaluation and Research Group on Protection in Controlled Atmosphere (GERPAC), 2013), and osmolality results were interpreted considering clinical tolerance of the preparation.
, 2013) , the acidification of the solution in GS-LDPE could therefore accelerate its degradation. PHMB eye drops was described to be stable for 45 days when frozen and for 14 days when refrigerated if prepared with 0. 01% benzalkonium chloride water  (McElhiney, 2013). The difference between stabilities of those eye drops to ours could be explained by the use of different excipient, since we used 0. 9% sodium chloride instead, considered as more isotonic, or alternatively the study was not performed for a longer time. Despite there being no other published data on ophthalmic formulations of PHMB, its stability was assessed in other pharmaceutical forms. For instance, Lucas et al. found that PHMB at 1 ppm in multipurpose CLes solution being stable after 30 days stored at -20 C, 5 C and 25 C  (Lucas, Gordon & Stratmeyer, 2009).
Improvement of Culture Conditions The composition of plant culture media is an important parameter for both growth and specialized metabolite production  [35, 36]. Here, the effects of mineral composition on the growth and AT accumulations were evaluated using four different culture media: Gamborg B5 (B5  [37] ), Linsmaier and Skoog (LS  [38] ), Murashige and Skoog (MS  [39] ) and Woody Plant Medium (WPM  [40] ). The ion contents of these basal media are presented in supplementary data (Table  S3 ). The main differences between the mineral bases of these media are the amount and form of the nitrogen and the abundance in anions, MS and LS being high in total nitrogen and WPM high in sulfate. LS and MS medium only differed by their vitamin composition. The HRLF15-2 line was used as elite line and both its growth and ATL production over 20 days were recorded.
Precursors Feeding Precursor feeding strategy using cheap precursors was evaluated using L-Phe, an early biosynthetic precursor at the entry point of the phenylpropanoid pathway, and ferulic acid, a late precursor at the entry point for the biosynthesis of coniferyl alcohol through monolignols pathway. Feeding experiments with young shoots of F. intermedia have shown that both L-Phe and ferulic acid are good precursors for lignan biosynthesis  [52]. Both L-Phe and ferulic acid cellular uptakes were assessed by their disappearance from the culture medium associated with a simultaneous transient cellular accumulation in fed HR followed by a decrease because of their metabolization (Figure  S4 ). L-Phe feeding resulted in a biomass decrease (Figure  6A ), reduced viability (data not shown) and, except for PPT, was associated with only a slight increase in ATL accumulation (Figure  6B -F, Table  S4 ).
MPT and MPTG Purification MPT and MTPG purifications were performed according the method described by Van Uden et al. (1992)  [62]. Their identification was confirmed by LC-MS and NMR. The data obtained are in full agreement with literature data for MPT  [62]  and for MPTG  [63] ). NMR spectra were acquired at 300 K on a Bruker (Bremen, Germany) Avance III 600 spectrometer (Magnet system 14. 09 T 600 MHz/54 mm) operating at 600. 17 MHz for 1H, using a TXI 5 mm z-gradients probe. The TOPSPIN (Bruker) software was used. Shim control was performed automatically by gradient shimming and final lineshape optimization (Topshim 1D procedure). 1 H-NMR spectra were obtained using a classical proton sequence (90 • proton pulse was calibrated to 7. 36 µs at -1 dB (18. 34 W)), 6602 Hz spectral width and 7 s relaxation delay.
4 µL of sample reconstituted in methanol at 10 mg/mL of engaged material were injected. UV spectra were recorded from 195 to 500 nm. The positive mode using an ESI source in the range of 50 to 1300 m/z at 1 Hz was used to acquire MS data. The parameters were as follows: capillary voltage 4. 5 kV, nebulizing gas at 1. 5 bar, drying gas heated at 200 • C, at 8 L/min. Data (MS and UV) were acquired with Compass 1. 3 software (Bruker) and MS areas were measured with Quant Analysis 2. 1 software (Bruker). Extracted ion chromatograms for DPT, PPT, PPTG, MPT and MPTG are presented in Figures S6-S10.
Acknowledgments. These research works are funded by the  French Research Agency (ANR)  regarding the research project  ARBRE  [Grant  ANR-17-CE10-0006 ], 2017-2021. ARBRE aims to develop French biorefineries as agile collaborative networks and supported by the  Industry 4. 0 paradigm. The authors would like to thank the project partners for their advice and comments regarding this work.
MATERIALS AND METHODS Breast cancer samples and gene expression profiling Our institutional series included 352 tumour samples from pretreatment invasive primary mammary carcinomas either surgically removed or biopsied. 28 The study was approved by our institutional review board. Each patient had given a written informed consent for research use. Samples had been profiled using Affymetrix U133 Plus 2. 0 human microarrays (Santa Clara, CA, USA). We pooled them with 34 public breast cancer data sets comprising both gene expression profiles generated using DNA microarrays and RNA-Seq and clinicopathological annotations. These sets were collected from the National Center for Biotechnology Information (NCBI)/Genbank GEO and ArrayExpress databases, and authors' website (Supplementary Table  1 ).
Gene expression data analysis Before analysis, several steps of data processing were applied. The first step was the normalisation of each set separately. It was done in R using Bioconductor and associated packages; we used quantile normalisation for the available processed data from non-Affymetrix-based sets (Agilent, SweGene, and Illumina), and Robust Multichip Average (RMA) with the non-parametric quantile algorithm for the raw data from the Affymetrix-based sets. In the second step, we mapped the hybridisation probes across the different technological platforms represented as previously reported. 29 When multiple probes mapped to the same GeneID, we retained the most variant probe in a particular data set. We log2 transformed the available TCGA RNA-Seq data that were already normalised.
27 Briefly, the CC analysis was performed in R using the Bioconductor package "ConsensusClusterPlus" 31 setting as input parameters 5000 repetitions, 80% item resampling (pItem), a number of groups (k) fixed to 4 (in order to have all data sets stratified with the same number of classes, 4 being the optimal number of groups for the TCGA cohort,  27  ) and the use of an agglomerative hierarchical clustering with ward criterion (Ward. D2) inner and complete outer linkage. We also applied the three major prognostic multigene classifiers of breast cancer: Recurrence score,  32  70-gene signature,  33  and Risk of Relapse score based on PAM50 subtype and proliferation Risk of Relapse (ROR-P). 2  Other signatures included the metagenes associated with immune cell populations such as T cells, CD8+ T cells and B cells defined by Palmer et al.
Such correlation between ICR classes and pCR rate was maintained in each molecular subtype separately (Supplementary Table  7 ). Based on these results and the MFS results, we postulated that the prognostic value of ICR classification could be mediated, at least in part, by its association with response to chemotherapy. Thus, we analysed its prognostic value in our MFS data set according to the delivery or not of adjuvant chemotherapy, which was informed for 2355 patients, including 1653 HR+/HER2-, 265 HER2+, and 437 TN. As shown in Supplementary Figure  5 , in the whole population the prognostic value was present in the chemotherapy-treated group (p = 1. 40E-02, log-rank test), but not in the chemotherapy-naive group (p = 0. 18); however, interaction was not significant (p = 0. 14). Analysis per molecular subtype revealed no prognostic value for ICR classification in both groups in the HR+/HER2-patients and no interaction; by contrast, interaction was significant (p = 4.
sUBJecTs anD MeThODs subjects We conducted a prospective multicenter cohort study. Twentysix patients from Germany, France, and the Czech Republic were screened for eligibility to participate in the study. Twenty-one patients (11 females) with genetically and clinically confirmed GD3, with a mean age of 17. 89 ± 10. 98 years (age ± SD), mean disease duration of 17. 4 ± 12 years, and mean age at disease onset of 3. 7 ± 5 years, who were able to perform at least one study task were included in this study. Patients' characteristics and correlations of clinical and oculomotor outcomes are listed in Table  1  and Table  S1  in Supplementary Material. Eleven patients were assessed at two time points (longitudinal analysis over 12 months). In these patients, data from the last visit of patients were used (Table  S1  in Supplementary Material).
Gaze-Holding Participants were asked to fixate a point of 0. 57° visual angle presented on a monitor without moving their head. The point was primarily positioned at eye level to allow fixation straight ahead, then eccentricity changed from 15° left to 15° right and 10° down. The stimulus was presented for 10 s at each position. The data analysis of slow and quick phases of the gaze-holding nystagmus and drift was performed, as described previously (8-10). Frequency, peak velocity (PV), and amplitude of the 2D vector of quick phases were analyzed.
statistical analysis We report mean, SD, and 95% confidence interval for continuous, absolute, and relative frequencies for categorical variables. Normality of data distribution was tested using the mean, median, SD, skewness, kurtosis, and box plots. As data were not normally distributed, related-samples Wilcoxon signed-rank test was run to determine if there were differences in measured scores between the initial examination and follow-up after 1 year. Non-paired Mann-Whitney U-tests were used to compare patients and healthy controls. For the group analysis, data from the follow-up visit of patients measured twice were used. For the longitudinal analysis, outcomes of 11 patients measured at two timepoints 1 year apart were compared. The two-tailed significance level was 0. 05. As this is an exploratory study, no correction for multiple testing was conducted.