dataesr/scientific-paragraphs-categorization huggingface dataset:
RT-PCR Quantitative values were obtained from the cycle number (Ct value) at which the increase in the fluorescence signal associated with exponential growth of PCR products started to be detected by the laser detector of the ABI Prism 7900 sequence detection system (Perkin-Elmer Applied Biosystems, Foster City, CA, USA), using the PE Biosystems analysis software (Perkin Elmer Applied Biosystems) according to the manufacturer's manuals. The precise amount of total mRNA added to each reaction mix (based on optical density) and its quality (i. e. , lack of extensive degradation) are both difficult to assess. We therefore also quantified TBP gene transcripts (Genbank accession NM_003194) encoding the TATA box-binding protein (a component of the DNA-binding protein complex TFIID) as an endogenous RNA control and normalized each sample on the basis of its TBP content.
We selected TBP as endogenous control, because of the moderate prevalence of its transcripts and the absence of any known TBP retropseudogenes (retropseudogenes lead to coamplification of contaminating genomic DNA and consequently interfere with RT-PCR, despite the use of primers in separate exons)  [26]. Results are expressed as N-fold differences in target gene expression relative to the TBP gene and termed 'N target =2 DCT ', where the ∆Ct value of the sample was determined by subtracting the Ct value of the target gene from the Ct value of the TBP gene. Primers for TBP and target genes were chosen by using Oligo 6. 0 software (National Biosciences, Plymouth, MN, USA). We scanned the dbEST and nr databases to confirm the total gene specificity of the nucleotide sequences chosen for the primers and the absence of single-nucleotide polymorphisms.
arabidopsis. org/) in each sample, expressed as reads per kilobase of transcript per million sequenced reads (RPKM), was calculated (see GEO accession number GSE79839). To validate our transcriptomic analysis, we first examined the expression of the MIR166g (AT5G63715) precursor previously shown to be upregulated in jba-1D/+ and the expression of three of its HD-ZIP III targets, namely PHB, PHV and CNA, previously shown to be downregulated in jba-1D/+  (Williams et al. , 2005). At both time points, MIR166g transcripts were undetectable in Col-0 and clv3-2 meristems (RPKM of 0), but reached RPKM values between 106 and 236 in the meristems of all mutant combinations in the jba-1D/+ background (Fig. 6A ). This pattern was specific to the MIR166g precursor and was not observed in any of the other eight MIR165 or MIR166 genes.
, 1999; Hobe et al. , 2003). We and others  (Fletcher et al. , 1999; Laufs et al. , 1998; Schoof et al. , 2000)  have proposed that meristem enlargement in clv3 mutants is the result of an increase in the stem cell population. Therefore, shifting the ratio between cell populations in the SAM towards more stem cells, we expected to see a high level of CLV3 transcripts in Fig. 6. Expression profiles of selected genes in the meristem of wild-type and mutants validate the mRNA-Seq analysis. (A) RPKM values of MIR166g, its HD-ZIP III targets and ZPR1, showing a high level of MIR166g and a low level of its targets in genotypes with the jba-1D/+ background, validating the mRNA-Seq analysis. (B) Correlation matrix for the expression of genes in cluster 687. The correlation coefficients for pairs of genes were subjected to two-way hierarchical clustering using Cluster Gene.
The white square marks the subset that includes CLV3, which is discussed in the text. (C) Heat map of selected genes co-expressed with CLV3 from cluster 687 (GEO accession GSE79839). Genes shown to be expressed exclusively in the CZ are underlined in red  (Yadav et al. , 2009). The heat map was produced by clustering the normalized values using the hierarchical clustering algorithm implemented in Gene Cluster (for details see the supplementary Materials and Methods). mutants with the clv3-2 background. Indeed, the RPKM values were 49 and 47 in clv3-2, and 47 and 124 in clv3-2 jba-1D/+ er-20, for 8-and 15-day-old meristems, respectively, whereas all other samples showed values in the range of 1. 3 to 3. 2 (GEO accession GSE79839). Furthermore, to correlate gene expression patterns with phenotypes and meristem functions, a k-means (k=1000) clustering algorithm was used to assign genes to expression clusters.
Out of the 76 genes that were highly correlated in expression with that of CLV3 and assigned to the same cluster (cluster 687; GEO accession GSE79839), seven were previously shown by in situ hybridization to be expressed exclusively in the CZ  (Yadav et al. , 2009). These seven genes validated our clustering analysis and suggest that our mRNA-Seq analysis identified many candidate stem cell-specific genes for future validation. To identify a more reliable core set of genes related to stem cell function, we further calculated the correlation coefficients for all possible gene pairs in cluster 687 and clustered the genes based on the Euclidean distance of their correlation coefficients using a hierarchical clustering algorithm. The result, represented as a heat map (Fig. 6B ), allowed us to select a group of 23 genes that were most highly correlated with the CLV3 pattern of expression.
ER regulates mitotic activity in the PZ The relatively low expression level of CLV3 and its co-expressed genes in jba-1D/+ and jba-1D/+ er-20 (Fig. 6C , Fig. S7 ; GEO accession GSE79839) suggests that in both mutants the increase in meristem size is either proportional for all zones, such that the CLV3 expression level is similar to that seen in Col-0, or results from an increase in the meristematic cell population outside of the CZ that does not express CLV3. Another possibility is an increase in the number of leaf primordia, leading to dilution of CLV3 mRNA. The cell division rate in the CZ is lower than at the meristem periphery  (Cockcroft et al. , 2000; Geier et al. , 2008; Grandjean et al. , 2004; Laufs et al. , 1998). To gain insight into the proliferation rate in the meristem of the different genotypes, we analyzed the expression patterns of mitotic activity marker genes.
Histones are the primary protein components of chromatin and their transcription is tightly coupled to DNA replication during S phase of the cell cycle  (Takayama and Toda, 2010) ; as such, they serve as a marker for cell division activity  (Geier et al. , 2008; Meshi et al. , 2000). The k-means analysis, presented as a heat map (Fig. 7A ), reveals that out of the 42 histone genes that showed expression in this mRNA-Seq analysis, 11 genes corresponding to the four core histones were assigned to cluster 628 (Table  S3 ; GEO accession GSE79839), which is also enriched with many genes involved in cell division. To categorize the functions of the 52 genes assigned to cluster 628, we searched for significantly enriched gene ontology (GO) terms using singular enrichment analysis, as implemented in agriGO (see the Materials and Methods).
7B , Table  S4 ). These analyses demonstrate that adding er to jba-1D/+ leads to an increase in mitotic activity at the meristem. Furthermore, our analysis reveals that Col-0 and jba-1D/+ exhibit similar expression patterns of stem cell genes (Fig. 6C ) and mitotic marker genes (Fig. 7B ) in both 8-and 15-day-old meristems, suggesting that the increase in meristem size in jba-1D/+ is proportional for all zones. Another interesting pattern of meristem-related gene expression was that of the TYPE-A RESPONSE REGULATOR genes ARR5, ARR6, ARR7 and ARR15 (Fig. 7C ), which are negative regulators of cytokinin signaling and meristem size, and are directly repressed by WUS  (Leibfried et al. , 2005). The triple-mutant meristems showed the lowest level of expression at both time points (GEO accession GSE79839) and the general expression pattern of the ARR genes resembled that of the three HD-ZIP III and ZPR1 genes (Fig.
6A ), with lowest expression in mutants of the jba-1D/+ background. In the k-means analysis, ARR5 and ARR6 were assigned to cluster 788 together with ZPR1 and ZPR4 (GEO accession GSE79839), suggesting a link between HD-ZIP III, ZPR and ARR genes. The SHOOT MERISTEMLESS (STM) TF functions in the meristem to prevent the premature incorporation of cells into 1618 differentiation pathways. Accordingly, it is expressed in both the CZ and PZ of the meristem and repressed in organ primordia  (Gallois et al. , 2002; Long et al. , 1996). To further investigate the ratio between domains in the meristem, we looked at the ratio of expression levels of the meristematic cell marker STM  (Geier et al. , 2008)  and the stem cell marker CLV3 (Fig. 7D ). When dividing the STM RPKM value by that of CLV3, genotypes with the clv3-2 background show the lowest ratio at both time points, implying that these meristems harbor a higher proportion of stem cells than wildtype meristem, whereas jba-1D/+ er-20 exhibits the highest ratio, implying that its meristem harbors a high proportion of meristematic cells.
Microscopy and histology Whole-plant images were captured using an Olympus SZX7 stereomicroscope. Images of transverse sections were captured using an Olympus IX8 Cell-R inverted microscope. SEM was performed by fixing tissue in methanol as described previously  (Talbot and White, 2013)  for examination in a JEOL 5410 LV scanning electron microscope. For histological analyses, seedlings were fixed in 4% formaldehyde fixative with 50% ethanol and 5% glacial acetic acid, vacuum infiltration, dehydrated, embedded in paraffin wax, sectioned at 8 μm thickness and stained with Toluidine Blue. SAM images were measured using ImageJ software (NIH). Statistical analysis of all measurements was performed using the non-parametric multi-comparison Steel-Dwass test due to unequal variance between the different genotypes using JMP 12 software (SAS).
Funding This work was supported by the  Israel Science Foundation  [ 1351/10  to T. M. ];  Vaadia-BARD  [ IS-4336-10R  to L. A. ]; the  MARIE CURIE  funded by the  European Commission  [ IRG 249270  to U. L. ];  Spain's Ministry of Economy and Competitiveness  and the  European Regional Development Fund (ERDF)  (' Una manera de hacer Europa ') [ BFU2012-31719  to H. C. ]; the  University Grenoble-Alpes (UGA-UJF)  and the  Centre National de la Recherche Scientifique  [CNRS-Higher Education Chair, position 0428-64; IUA Chair to C. C. C. ]. Deposited in PMC for immediate release.
Data availability The mRNA-Seq datasets discussed in this publication have been deposited at Gene Expression Omnibus with accession number GSE79839. Movies are available at Figshare: Movie 1, http://dx. doi. org/10. 6084/m9. figshare. 3084610; Movie 2, http:// dx. doi. org/10. 6084/m9. figshare. 3084613; Movie 3, http://dx. doi. org/10. 6084/m9. figshare. 3084583; Movie 4, http://dx. doi. org/10. 6084/m9. figshare. 3084586; Movie 5, http://dx. doi. org/10. 6084/m9. figshare. 3084592; Movie 6, http://dx. doi. org/10. 6084/m9. figshare. 3084595; Movie 7, http://dx. doi. org/10. 6084/m9. figshare. 3084604; Movie 8, http://dx. doi. org/10. 6084/m9. figshare. 3084607.
Milk yield of primiparous lactating dairy cows Daily MY was recorded for the five primiparous cows, from calving to the drying-out period. As expected, the MY was significantly different at each mammary gland biopsy timepoint of mammary biopsies (30, 90, 150 and 250 days) with 29. 9 kg/day, 34. 3 kg/day, 32. 9 kg/day and 19 kg/day, respectively (p<0. 05) (Figure  1 ). The mean of daily MY described a classical lactation curve, with a peak of production at ≈ 60 days post-calving. Analysis of milk composition data showed that fat and protein yields varied according to MY, as expected during lactation in primiparous dairy cows (Table  2 ). Furthermore, somatic cell count (SCC) values were less than 250x10 3 cells / mL throughout lactation, showing the cows and their mammary glands were healthy.
Gating strategy for flow cytometry data analysis To validate the multicolor panel of the four antibodies used in the present study, coupled with four different fluorochromes, we performed single cell staining with each antibody (Table  3 ) and Fluorescent Minor One. To develop this technique, essential to set up our multicolor assays, we used a manual compensation matrix based on the median fluorescence intensity procedure. We also ensured that only single living cells were analyzed, by eliminating cell aggregates and dead cells from our analysis. In order to eliminate aggregates, we performed doublet exclusion using FSC-H/A and SSC-H/A parameters. To discriminate between live cells and dead cells, we used PI staining. This technical strategy is essential to analyze each cell-surface marker in single living cells (Figure  5A ).
The prerequisites for our study were to ensure that mammary explant samples were representative of a lactating mammary gland. Using five primiparous dairy cows, we first monitored their zootechnical data in order to ensure their MY responses and the quality of the milk composition. A classical lactation curve is defined by a peak in milk production between 30 and 90 days of lactation, followed by a decrease in milk production. To validate the mammary gland samples prior to the phenotypic characterization of mammary cells, we observed the morphology of the tissue obtained by biopsy and analyzed the expression of the CK19 gene (a conventional marker of mature alveolar cells  [27, 28] ). As expected, we observed an increase in the surface of luminal spaces in alveoli at 90 days of lactation, followed by a decline, which correlated with the decline in MY.
Procedures and measurements The patients' medical records were analyzed to obtain data on drugs, preexisting diabetes, hypertension, stroke, peripheral vascular disease or coronary artery disease (defined by history of myocardial infarction, angina pectoris or requirement for coronary artery bypass or angioplasty). Sex, age and body mass index were collected at inclusion and the 4-variable MDRD equation was used for calculation of the baseline estimated GFR (eGFR). Blood samples were collected at inclusion (M0). BNP, NT-proBNP, Troponin T (TnT) were detected in ethylenediaminetetraacetic acid plasma (EDTA) using a fluorescence immunoassay (Triage, Biosite) for measuring BNP and electro-chemiluminescence (Elecsys, Roche diagnostics) for measuring NT-proBNP and TnT. The blood samples were centrifuged and kept frozen at -80°C until 12 months after inclusion.
Statistical analyses Statistical analyses were performed with Statview software version 5. 0 (SAS Institute). A p-value<0. 05 was considered significant. Comparisons were performed using the non-parametric Mann-Whitney U test. Receiver operator characteristic (ROC) curves for BNP and NT-proBNP were estimated to determine cut-off points at which sensibility and specificity was maximized. By stratifying the patients in two groups according to the plasma BNP and NT-proBNP levels above or below the cut-off values, survival curves were determined using the univariate Kaplan-Meier calculation and the significance between the curves tested using logrank test. Kendall's tau coefficient was used to test for associations between BNP and other variables for inclusion in multivariate models.
Acknowledgments The authors thank  Dr Catherine Bessin  and  Dr Olivier Drouineau  ( Nephrology Department, Dieppe Hospital, Dieppe, France ), for their kind help in including patients. All authors have read and approved the manuscript. The material submitted has been approved by an institutional ethical board, is the result of primary research, has not been previously reported, and is not under consideration for publication elsewhere. The results presented in this paper have not been published previously in whole or part, except in abstract form.
The capsule assembly is Wzx/Wzy dependent. To further clarify the relation between the capsule and LOS, we investigated their transport and assembly pathway. In the gene cluster previously identified (Fig. 2c ) Ccan_23200 shows sequence similarity to Wzx, the O-antigen flippase involved in the transport of O-antigen units to the periplasm across the inner membrane  43, 56  while Ccan_23280 has sequence similarity to the O-antigen polymerase Wzy involved in the polymerization of the O-antigen repeating units, thus suggesting that the C. canimorsus 5 O-antigen and/or the CPS are synthesized by a Wzx/Wzy dependent pathway  43. In order to verify this, we generated a Ccan_23200 (putative wzx) mutant strain and analyzed its LOS and CPS by western blot. Mutation of wzx turned out to be polar but could be complemented by wzx plus Ccan_23210 (Supplementary Data S1 and Supplementary Fig.
canimorsus 5 genome  51. Query sequences were obtained from the NCBI database. All available search sequences for a corresponding gene of interest were used. The highest scoring subjects over all the searches have been annotated as corresponding enzymes. Analysis of synteny of the LOS/CPS C. canimorsus loci was obtained from the MicroScope Microbial Genome Annotation and Analysis Platform (https://www. genoscope. cns. fr/agc/ microscope/home/index. php)  76. Putative orthologous relations between two genomes are defined as gene couples satisfying the bi-directional best hit (BBH) criterion or a BlastP alignment threshold, a minimum of 35% sequence identity on 80% of the length of the smallest protein. These relations are subsequently used to search for conserved gene clusters, synteny groups (syntons), among several bacterial genomes.
Statistical analysis. Statistical analyses were realized using the software GraphPad Prism by one-way ANOVA test followed by a Bonferroni test. LOS isolation. C. canimorsus were harvested from 600 SB plates in PBS and washed with ddH 2 O, ethanol (300 ml) and acetone (300 ml), followed each time by centrifugation at 18000 × g for 30 min. LOS used for western blot analysis was isolated from C. canimorsus 5 wt and Y1C12 mutant as described in ref. 36. Alcian blue and silver staining of proteinase K-resistant structures. Bacteria treated with proteinase K as described above were loaded on 15% Tris-glycine SDS polyacrylamide gels. Following electrophoresis, the gels were stained first with Alcian blue (Sigma) (0. 125% Alcian blue in 40% ethanol-5% acetic acid) and then with silver as described in ref.
Acknowledgements We thank  E. Maes  and the  PAGés platform (Plateforme d' Analyses des Glycoconjugués. UMR8576 ,  Univ. Lille1 ,  CNRS, 59000 Lille ) for their scientific and technical contributions,  Prof. Henning Stahlberg  ( C-Cina, Biozentrum of the University of Basel ) for his support,  Prof. Ulrich Zähringer  ( Leibniz-Center for Medicine and Biosciences, Borstel, Germany ) for his comments and suggestions and  P. Manfredi  ( Biozentrum of the University of Basel ),  K. Hack  and  E. Lawarée  ( University of Namur ) for stimulating discussions. This work was financed by advanced grant  293605-CAPCAN  from the  European Research Council  and grant  SOC 1510582  from the  Walloon Region  to G. R. C. F. R. is a post-doctoral fellow "chargé de recherche" of the  Belgian National Fund for Research (FNRS).
C. Gafchromic measurements Gafchromic EBT3 films (Ashland Inc, Covington, KY) were evaluated using FilmQA Pro software (Ashland Inc. ) with a flatbed scanner (Epson 11000XL, US Epson, Long Beach, CA) 24 hrs after the irradiation in order to stabilize their responses. To optimize our readings, and especially the flatbed scanner homogeneity, a template is centered on the surface to limit the zone of digitalization (which allows us a "landscape orientation" of 20 × 25 cm 2 ). The film is placed under a 2 mm plate of glass placed above the films to hold them flat and the dose response is established according to the multichannel method. As we use these films and software for pretreatment verifications, the response of our batch (A03031407) was established in a 6 MV standard beam (Clinac 21EX, Varian Medical Systems, Palo Alto, CA).
Therefore, we designed the PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) randomised controlled trial to test the hypothesis that for people with acute ICH associated with the use of antiplatelet therapy, platelet transfusion compared to standard care without platelet transfusion reduces death or dependence. One other similar trial is ongoing (NCT00699621). The PATCH trial has been registered (Netherlands Trial Register NTR1303), its protocol has been published  [18] , and we now describe the final statistical analysis plan, which was written and submitted without knowledge of the outcome data.
Data collection Investigators were asked to record patient characteristics and demographics before randomisation, which only required the patient's age and pre-ICH antiplatelet therapy to be specified. Brain computed tomography (CT) or magnetic resonance imaging (MRI) ± angiography was performed in routine clinical practice at hospital admission. Repeat brain imaging was performed as a trial procedure and was intended to be the same modality as baseline scan, done at 24 ± 3 hours after randomisation. Diagnostic and 24-hour brain imaging studies were obtained in DICOM format from trial sites, and analysed centrally in Amsterdam. Investigators collected information about the occurrence of serious adverse events/reactions during hospital admission and the date and destination of discharge. Neurologists or research nurses who were trained and blinded to treatment allocation collected follow-up data at 3 months after randomisation by use of either structured telephone interview or face-to-face interview.
Interim analyses and safety reporting The Data Safety Monitoring Board (DSMBsee Appendix) consisted of three independent trial experts (one statistician, one neurologist, and one expert in vascular medicine) to monitor safety and perform an analysis of unblinded effectiveness data at one time point after inclusion of 100 patients in the trial. At the time of inclusion of the 100 th patient, SAEs needed to be recorded and reported to the trial coordinating centre, and the DSMB needed to be reconstituted (Appendix), by which time 160 patients had been included in the trial and an interim analysis could be performed on the first 154 patients for whom both outcome and SAE data were available. The DSMB were provided with a report prepared by an independent statistician that included baseline variables [gender, age, antiplatelet therapy, and National Institutes of Health Stroke Scale (NIHSS) score], SAEs, the primary outcome, and a distribution of the mRS in each of the arms of the trial unblinded to the treatment group.
The DSMB was instructed in a charter to look at safety (deaths and the number of SAEs in both groups) and efficacy (primary outcome, dichotomised 0-3 vs. 4-6, using a Haybittle-Peto stopping rule with a p value set at 0. 001  [23] ). The DSMB assessed the unblinded data in a closed session, independent of the investigators, in October 2015. The DSMB had not been provided with a pre-specified threshold for futility. Additionally the DSMB was asked to advise the executive committee on possible continuation of the trial beyond its pre-specified sample size if analyses showed a possible signal of efficacy. By the time the DSMB gave its final advice to the executive committee, the trial had just reached its pre-specified sample size of 190 patients. The verdict of the DSMB was that their advice was without consequence for the study and to not include more patients beyond the pre-specified sample size.