dataesr/scientific-paragraphs-categorization huggingface dataset:
The corresponding buffer background measurement for producing the background-subtracted curve was collected at greater than 1. 5 column volumes. Buffer subtractions and all other subsequent analysis were performed with the program ScÅtter (http://www. bioisis. net/scatter). The SAXS curves were analzsed with the program DAMMIF from the ATSAS suite  [29]. The program DAMMIF generates ab initio bead models by simulated annealing that describe the experimental scattering curves. An average model from the results of seven independent DAMMIF runs was calculated using DAMAVER from the ATSAS suite.
After washing, the beads-coupled proteins were eluted with Laemmli sample buffer and separated by SDS-PAGE. Co-immunoprecipitation of Lu-Fc proteins was detected using an anti-Fc immunoblot (II). As Input, samples from the cell culture supernatants were taken before incubation with beads (I); (F) flow cytometry binding studies, DyLight488-labeled GST-CNF1 was pre-incubated with different Lu-Fc proteins respectively followed by an incubation with a suspension of HeLa cells (3 × 10 5 cells in 1 mL medium). As positive control cells were incubated with DyLight488-labeled CNF1 without preincubation with Lu-Fc. After washing three times with PBS, cells were subjected to flow cytometry measurements. The bound fluorescence is shown in comparison to the positive control, which was set to 100%. Data shown represent three independent experiments + standard deviations.
Acknowledgments: We thank  Jürgen Dumbach  for excellent technical assistance. We thank  Diamond Light Source  for access to beamline B21 (MX15381) that contributed to the results presented here. The research leading to these results has received funding from the  European Community 's  Seventh Framework Program  ( FP7/2007-2013)  under grant agreement No. 283570  (for BioStruct-X). Funding: DFG Schm 9-1 (FR),  DFG SFB850  ( C2 , GS).
Lipids were then dried under argon and quantified after methanolysis by GC-FID as described above. Extraction and quantification were performed from 4 to 5 independent biological repeats for the MTX condition, three to five independent biological repeats for MTX + Met and three independent biological repeats for MTX + Pi-choline conditions. To correct inherent variations from one culture to another  (Meï et al. , 2015) , a control was systematically run for each experiment and data were analyzed as fold change versus the corresponding controls. Quantifications were normalized by multiplying the experiment/control ratio by the average value of the control. Statistical analyses were performed with GraphPad Prism software using unpaired t-test with α = 5%.
1, product ion m/z 86. 1). AdoMet was identified from its retention time (3 min) and by the MS2 signal corresponding to the loss of the Met group (parent ion m/z 399. 1, product ion m/z 250. 1). AdoHcy was identified from its retention time (2. 7 min) and by the MS2 signal corresponding to the loss of the Hcy group (parent ion m/z 385. 4, product ion m/z 250. 1). Quantification were performed from at least three independent biological repeats for each condition. Statistical analyses were performed with GraphPad Prism software using unpaired t-test with α = 5%.
Quantitative RT-PCR Real-time quantitative RT-PCR experiments were performed using cDNA synthesized from total RNA isolated from control and treated Arabidopsis cells, according to the manufacturer instructions (RNeasy Plant Mini Kit, Qiagen). Amplification of contaminating DNA was prevented by DNAse treatment of RNA samples. Specific primer sequences were designed for each tested gene (Supplementary Table  2 ). The realtime PCR reactions were carried out on a Rotor-Gene 3000 instrument (Corbett Research) using SYBR Green JumpStart Taq ReadyMix (Sigma-Aldrich). Quantification of gene expression was performed using the comparative Ct method within the Rotor-Gene 3000 Software. Each data were normalized with three reference genes chosen for their absence of variation in the MTX and nitrogen-deprived conditions (ACT7-At5g09810; UBQ5-At3g62250; ARP1-At1g43170).
e. , galactolipids and phosphatidylglycerol, were almost not affected (Figure  3D ). Surprisingly, we did not observe any decline of the amount of PC despite the nearly twofold decrease of the Picholine concentration. On the contrary, like most phospholipids, PC showed a tendency to increase. These results indicate that All the measurements were made after 72 h of treatment. The data are means ± SD of five independent biological repeats for each condition. Significant differences (P < 0. 05) are shown by an asterisk and were calculated by an unpaired multiple t-test using GraphPad Prism software. the arrest of cell division following MTX treatment was not accompanied by a significant membrane breakdown, and that the resulting increase in lipid content was largely due to TAG synthesis. It is likely that in such a situation where the expansion of membranes was strongly reduced, the remaining level of Pi-choline was sufficient to supply the required PC turnover.
Thermoanalysis Differential Scanning Calorimetry (DSC) analysis was performed using a Mettler DSC-822E instrument (Mettler Toledo, Novate Milanese, Italy) under a nitrogen flow rate of 80 mL/min. The analysis was carried out in the range from -20 to 200 • C at a heating and cooling rate of 10 • C/min. By considering the second heating cycles in the thermograms, the glass transition temperature (T g ) was evaluated by analyzing the inflection point, while the melting temperature (T m ) and crystallinity (X c ) was evaluated by analyzing the endothermic peak. X c was determined by considering the value of the melting enthalpy of 146 J/g for the 100% crystalline PHB. Both characterization tests were carried out on five replicates for each kind of sample and the data were presented as mean ± standard deviation.
Thermoanalysis Differential Scanning Calorimetry (DSC) analysis was performed using a Mettler DSC-822E instrument (Mettler Toledo, Novate Milanese, Italy) under a nitrogen flow rate of 80 mL/min. The analysis was carried out in the range from -20 to 200 °C at a heating and cooling rate of 10 °C/min. By considering the second heating cycles in the thermograms, the glass transition temperature (Tg) was evaluated by analyzing the inflection point, while the melting temperature (Tm) and crystallinity (Xc) was evaluated by analyzing the endothermic peak. Xc was determined by considering the value of the melting enthalpy of 146 J/g for the 100% crystalline PHB. Both characterization tests were carried out on five replicates for each kind of sample and the data were presented as mean ± standard deviation.
Polymer Characterization: After the end of the experiment, the biomass was separated from the liquid supernatant via centrifugation, and was frozen and lyophilized. The dry biomass was decreased with ethanol and the polymer was extracted using chloroform. The weight average molecular mass (Mw) and the polydispersity (Pi; Mw/Mn) values of the extracted homopolymer were determined by gel permeation chromatography (GPC). The Mw was 627 ± 13 kDa and Pi was 2. 66 ± 0. 13 kDa (Table  1 ). Differential scanning calorimetry (DSC) analysis was carried out to determine the glass transition temperature (Tg), melting temperature (Tm), and crystallinity (Xc) of the PHB samples. Analysis of the obtained data showed that the Tg of the produced PHB was 1. 0 ± 0. 6 °C and the Tm was 177. 6 ± 0. 6 °C, while Xc was 70.
Polymer Characterization: After the end of the experiment, the biomass was separated from the liquid supernatant via centrifugation, and was frozen and lyophilized. The dry biomass was decreased with ethanol and the polymer was extracted using chloroform. The weight average molecular mass (Mw) and the polydispersity (P i ; Mw/Mn) values of the extracted homopolymer were determined by gel permeation chromatography (GPC). The Mw was 627 ± 13 kDa and P i was 2. 66 ± 0. 13 kDa (Table  1 ). Differential scanning calorimetry (DSC) analysis was carried out to determine the glass transition temperature (T g ), melting temperature (T m ), and crystallinity (X c ) of the PHB samples. Analysis of the obtained data showed that the T g of the produced PHB was 1. 0 ± 0. 6 • C and the T m was 177. 6 ± 0.
4 deriving matrix H can provide higher prediction accuracy than either genomic or pedigree-based prediction. In plants, the ssGBLUP approach proposed by  Ashraf et al. (2016)  has been used with a limited number of lines. The approach has not been tested on large datasets, e. g. , every cropping cycle, CIMMYT's Global Wheat Program (GWP) generates thousands of new breeding lines that are candidates for field evaluation. Applying GS in the GWP is economically feasible (1) when advancing breeding lines in the first preliminary yield trials to predict the performance of the selected lines in multi-environment trials or (2) for predicting a selected set of lines in different international target environments using as a training set the parents evaluated in Mexico and the progeny to be predicted in international environments such as those in South Asia.
Experimental data The data set included a total of 58,798 wheat lines that were evaluated at the Norman E. (2009) (2010) (2011) (2012) (2013) (2014) (2015) (2016). Some of the lines were also evaluated under the same conditions in South Asia (Jalbapur, Ludhiana and Pusa in India; Faisalabad in Pakistan; and Jamalpur in Bangladesh) during 2013-2016. Original data from each year comprise a large number of trials, each established using an alpha-lattice design with three replicates. The field management conditions under which each trial was established in each year are described in Table  1. The conditionslocation combinations will be referred to as environments. Table  2  shows the number of lines evaluated in each environment. The basic model fitted to each of the 12 environments described in Table  2  comprises the random effects of the trials, the random effects of the replicates within trials, the random effects of the incomplete blocks within trials and replicates, and the random effects of the breeding lines.
A pedigree relationship matrix (A) for the 58,798 individuals was computed using a modified version of the software 'pedigreemm'  (Bates and Vazquez, 2009 ) that accounts for selfpollination; the latest version of the routines can be found at https://github. com/Rpedigree/pedigreeR. Given the dimensions of A, it is difficult to hold it in RAM memory and compute it. Appendix A shows the small R script (R Core Team, 2016) that was used to obtain and store the relationship matrix. It uses results from partitioned matrices to obtain the result and speed up the computations; R was recompiled from source and linked against OpenBLAS (http://www. openblas. net ). For further details on the computations, see Appendix A. In total, 29,484 individuals were genotyped using Genotyping by Sequencing (GBS) (e.
Software The models described above were fitted using a modified version of the BGLR package (de los Campos and Pérez-Rodríguez, 2015). The package was modified in order to accept as inputs big. matrix objects created using the bigmemory package  (Kane et al. , 2013). The bigmemory package was used to handle the huge matrices that have to be used during the analysis and also to take advantage of what in computer science is known as shared memory. Once loaded into RAM memory, the data can be accessed from several processors, making it possible to perform a cross-validation relatively easily.
This makes the models and methods developed by Misztal et al. (2009) , Legarra et al. (2009)  and Aguilar et al. (2010;  2011)  very attractive for predicting unobserved and nongenotyped plants. In a recent article, Fernando et al. (2014)  proposed a single-step Bayesian regression strategy that allows using all genotyped and non-genotyped individuals by means of imputed marker covariates for non-genotyped individuals. The advantage of the Bayesian approach over the single-step BLUP is that it does not require computing the inverse of G. However, this modelhas not yet been applied to realistic datasets. The single-step approach of Misztal et al. (2009) , Legarra et al. (2009)  and Aguilar et al. (2010;  2011)  was used in dairy cattle studies and first applied to plant breeding data by Ashraf et al.
ACKNOWLEDGMENTS We are grateful to field and lab workers of CIMMYT's  Global Wheat Program  and to national program researchers who collected the data used in this study. This work was funded by  USAID Feed the Future Innovation Lab  for applied Wheat Genomics with headquarters at  Kansas State University  in collaboration with  CIMMYT  and their partners in South Asia, specifically in India and Pakistan. We also thank the  Bill and Melinda Gates Foundation  for providing financial support for genotyping the materials used here.
4% were annotated as hypothetical proteins. No genes for TDA biosynthesis were predicted. Genes for flagellar assembly are present. Genes for pilus assembly, type II and type IV secretion systems, and 20 methyl-accepting chemotaxis proteins indicate that chemotaxis and attached lifestyles could be adaptive features in this species, although no genes for quorum sensing were predicted. Several copies of phage major capsid proteins, phage portal proteins, and phage terminases demonstrating prophage sequences were found in the chromosome, but no clustered regularly interspaced short palindromic repeat (CRISPR) region was found. Its closest relative is Phaeoabcter arcticus, with which it shares 98. 7% 16S rRNA identity and 3,021 putative orthologs (54% of its genes). Accession number(s). This whole-genome shotgun project has been deposited at DDBJ/ENA/GenBank under the accession no.
Endocrine Receptor positive, HER2-negative EBC The decision to give adjuvant chemotherapy in addition to ET is debated among women with ER-positive, HER2-negative EBC. Similar decisional process should be made if the standard clinical, biological or genomic risks are to be used, irrespective of age. In a review data from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database of >40,000 women aged ≥65 years with EBC (11% received chemotherapy), no survival benefit was observed in ER-positive EBC  [43]. Identifying patients with low-risk of recurrence having low absolute benefit from chemotherapy based on multi-gene testing, may reduce the unnecessary exposure and toxicity from chemotherapy. Unfortunately, very few data are available in older patients. A study on trends in 21-gene recurrence score (RS) assay use among 132,222 women aged 66-74 and 75-94 years with BC post-surgery revealed no change in chemotherapy use despite increased RS testing and associated cost in patients ≥75 years  [44].
Recent SEER database study (30% of patients aged ≥70years) reported a high BC-specific mortality for older patients with either no 21-gene assay performed or a RS ≥18, but not <18  [45]. In a randomised phase III study of 6,693 women with EBC, chemotherapy provided no 5-year survival or recurrence benefit among patients with high clinical but low genomic risk (1% were >70 years) using the 70-gene signature  [46].
stephensi bites. For the determination of An. stephensi infection status, mosquito cephalothoraxes were dissected and submitted to mass spectrometry analyses and DNA amplification for molecular analysis. Spectra were grouped according to mosquitoes' infection status and spectra quality was validated based on intensity and reproducibility within each group. The in-lab MALDI-TOF MS arthropod reference spectra database, upgraded with representative spectra from both groups (infected/non-infected), was subsequently queried blindly with cephalothorax spectra from specimens of both groups.
Thus, the development of a consensual alternative tool for rapid and inexpensive identification of mosquitoes, and also for the determination of their infection status, appears important for the development of malaria epidemiological surveillance. In recent years, matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been used for the identification and classification of microorganisms  [15, 16] , and it has also been applied in the identification of arthropods  [7] , including mosquitoes  [17] [18] [19]. It requires the creation of a reference spectra database obtained from organisms unambiguously identified by morphology and molecular biology reference methods. More recently, MALDI-TOF has been described as a promising alternative for the detection of microorganisms in arthropods.
MALDI-TOF analysis and database creation Spectrum quality was validated by assessing its general intensity, the smoothness of the peaks, the flatness of baseline and its reproducibility compared to other spectra of the same categories. Poor quality spectra were excluded from the analysis. Spectra reproducibility of CTs from An. stephensi specimens molecularly defined as P. berghei-infected or non-infected was evaluated by comparing the average spectra of each sample within its respective group using ClinProTools 2. 2 and Flex analysis v. 3. 3 software (Bruker Daltonics, Germany). Reference spectra (MSP, Main Spectrum Profile) were generated by the automated function of the MALDI-Biotyper software v3. 0 (Bruker Daltonics, Germany) by combining the results of the spectra of at least two specimens per condition in order to create a database.
MSP were produced based on an unbiased algorithm, taking into consideration the peak position, intensity and frequency. Spectra from thirty control mosquitoes were selected based on their reproducibility and intensity for all further MS analyses. Random spectra of good intensity and good reproducibility of specimens from each batch (infected/ non-infected) were loaded in MALDI-Biotyper 3. 0 software to create a reference spectra database. Twelve spectra from control An. stephensi were added to the custom database, as well as six spectra of infected specimens and two spectra of exposed but PCR-negative specimens.
MALDI-TOF MS biomarker mass set To determine the CT differential peaks between An. stephensi, infected or not with P. berghei, the MS spectra from both groups were loaded into ClinProTools 2. 2 software. The software was used to generate a peak list for each group in the 2-20 kDa mass range and to identify discriminating peaks. The parameter settings in Clin-ProTools 2. 2 software for spectra preparation were as follows: a resolution of 800 ppm; a noise threshold of 3. 00 (intensity arbitrary unit); a maximum peak shift of 800 ppm and a match to calibration peaks of 20%. For the peak calculation, peak peaking was performed on single spectra with a signal-to-noise threshold of 3. 00 and an aggregation of 800 ppm. The spectra were then analysed with the genetic algorithm (GA) model, which displayed a list of discriminating peaks  [6].
Manual inspection and validation of the selected peaks by the operator gave a "recognition capability" (RC) value together with the highest "cross-validation" (CV) value. These values reflect the ability to distinguish the different spectra groups based on the chosen discriminatory peaks. Genetic Algorithm settings are optimized to provide the highest RC and CV values. All reference spectra from infected and non-infected An. stephensi were imported into ClinPro-Tools software, in order to detect the presence of discriminating peaks between the spectra of infected and non-infected CTs.
Blind tests The remaining CT spectra of each group after exclusion of those entered in the database were submitted to a blind test analysis. This blind test was performed against our in-lab database, composed of the present CT spectra from P. berghei-infected and non-infected An. stephensi, and also spectra from other arthropod species listed in Table 2  [12, [15] [16] [17] [18]. The identification level of significance was determined using the log score values (LSVs) given by the MALDI-Biotyper software v. 3. 3. , corresponding to a matched degree of signal intensities of mass spectra of the query and the reference spectra. LSVs ranged from 0 to 3. LSVs allow good evaluation of the reproducibility between a queried spectrum and a reference spectrum as it is the result of thorough comparison of peaks position and intensity between those two spectra.
MALDI-TOF analysis To appraise water-crushing reproducibility, CT MS spectra of non-infected An. stephensi were submitted to MALDI-TOF MS analysis. Afterwards, the comparison of the MS spectra of infected and non-infected An. stephensi with Flex Analysis and ClinProTools software indicated correct reproducibility of the protein profiles of CTs from mosquitoes of the same group (Fig. 2 ). Nevertheless, mild variations were still observed between spectra of the same group. For this reason, spectra selection for the database was supported by the creation of a dendrogram. Dendrograms are based on the results of Composite Correlation Index matrix (CCI). CCIs are calculated by dividing spectra into intervals and comparing these intervals across a data set. The composition of correlations of all intervals provides the CCI, which is used a parameter that defines the distance between spectra.
A CCI match value of 1 represents complete correlation, whereas a CCI match value of 0 represents an absence of correlation. Spectra chosen for the database upgrading were from different clusters, therefore representing the whole group, despite its relative heterogeneity. Visual comparison of MS profiles between the two groups revealed a few specific distinct peaks. Precise determination of discriminatory peaks between the two categories was then assessed using the Clin-ProTools software. In order to distinguish mosquitoes according to their infection status, 20 spectra from P. berghei-infected mosquitoes were compared.
3 ). The selected peaks of the Genetic Algorithm displayed recognition capability and cross validation values of 100 and 98. 72%, respectively. The upgraded MS reference database containing the 20 new spectra added in this study was queried blindly, resulting in 100% correct species-level identification and 98. 75% correct identification regarding the infection status for all tested samples, with LSVs ranging from 1. 347 to 2. 908. A total of 13/14 specimens considered as infected based on molecular analysis matched with reference spectra of P. berghei-infected An. stephensi. All control specimens were identified as non-infected by MALDI TOF MS. Also, mosquitoes exposed to parasitized mice but Plasmodium PCRnegative were identified as non-infected by MALDI TOF MS. Indeed, 100% of these spectra matched with the reference spectra of non-infected An.
Discussion The present work shows preliminary evidence that MALDI-TOF technology can be used for Plasmodium detection. Anopheles stephensi and Plasmodium berghei ANKA is one of the most frequently used pairs for experimental models involving this murine parasite  [26]. The blood smears performed on day 4 post-infection showed a low parasitaemia, as the average of the six blood smears was approximately 1% of infected red blood cells. However, approximately 5% of the parasites were in gametocyte form, some of them starting to deteriorate, highlighting the very short time window during which mosquitoes could be fed on the mice. Published literature Fig. 3  Comparison of MALDI-TOF MS profiles of mosquitoes infected or not by Plasmodium berghei using ClinProTools software. Red and green profiles correspond to average spectrum of control and infected mosquitoes respectively.