dataesr/scientific-paragraphs-categorization huggingface dataset:
This testifies that the radius of co-location used in TROPOMI TOC validation exercises should be as small as possible to ensure that the same air parcels are compared, while at the same time reserving a sufficient amount of co-location points, as was already demonstrated for GOME-2 by  Verhoelst et al. (2015; their Fig. 11). Investigating the optimal solution for the distance criterion, the closest distance between the projection of the TROPOMI's central pixel and the station's location for all the available co-locations of each GB station were studied. The dataset for this investigation consisted only of the closest co-locations found within 50 km for each satellite orbit and its statistical analysis showed that the median of the closest distance spans between 2 and 3 km, while its 75th percentile goes up to 4 km.
, 2018; Lerot et al. , 2018) , no data from CCD pixels 1 and 2 are available, due to the lack of cloud information. As it is reported, this is caused by a misalignment of Band 3, used for the total ozone retrievals (450 pixels per scan line), and Band 6, used for deriving the cloud altitude information (448 pixels per scan line), which led to the application of a shift of two detector pixels between the two bands. Therefore, due to the lack of cloud information for the first two pixels, the respective data could not be analyzed. Daily values of TOC retrieved from the WOUDC and the NDACC databases were widely used in previous studies for GOME2/Metop  (Koukouli et al. , 2015a) , IASI/Metop  (Boynard et al. , 2018) , OMI/Aura  (Garane et al. , 2018) , and SBUV/NOAA  (Labow et al. , 2013)  data validation.
In addition to daily values, individual GB measurements from Eubrewnet and the Canadian Brewer Network are also used in this study. Thus, the effect of the time difference of the sensing between satellite and ground-based measurements had to be investigated. For this purpose, the mean percentage differences were computed for all co-located measurements with maximum temporal differences ( t max ) varying between 5 and 60 min, keeping the search radius limit to 10 km. An example is presented in Fig. 2  for a middle latitude Eubrewnet station (Hobart, Australia, 42. 9 • S, 147. 3 • E), showing the mean and the standard error of the comparisons versus the t max (blue data points with error bars). In this figure it was chosen to show the standard error instead of the standard deviation to take into account the effect of the number of co-locations for each case.
The comparison between TROPOMI OFFL TOC and the Brewer GB measurements is presented in Fig. 3  for the example of the station in Manchester, UK, utilizing these coincident criteria. The blue open circles represent the comparisons of the satellite data to the individual measurements of the particular site (downloaded from Eubrewnet) with a maximum temporal difference of 40 min, while the red dots stand for the respective GB daily data acquired through the WOUDC repository. All co-locations included in the plot have a maximum search radius of 10 km and refer to the same time period of operation. In both cases, the mean bias is negative, even though it is different by 0. 7 %, but the standard deviation of the mean is only slightly different between the two data series, which proves that even when daily means are used for the TROPOMI validation, the statistical results of the comparison are equally reliable.
The effective temperature is the only exception in the generally very smooth picture, which when lower than 210 K or www. atmos-meas-tech. net/12/5263/2019/ Atmos. Meas. Tech. , 12, 5263-5287, 2019  higher than 250 K causes biases of up to ±4 %, especially in the Dobson comparisons where it has a stronger effect, as described in  Koukouli et al. (2016). Finally, in Table  2  the overall global statistics, as well as the latitudinal statistics for the two TOC products and their comparisons to Dobson, Brewer and SAOZ GB measurements, are summarized. The mean bias of each dataset is listed in this table, along with the mean standard deviation, which is the mean of the standard deviations of the (global or latitudinal) means. In all comparisons seen here the mean bias of the two products is far below the requirements, not exceeding +1.
The other important updates are briefly discussed in Sect. 2. 1. 1 and are summarized in Table  3. Furthermore, it was found that the deviation between the two algorithms in this particular latitude bin is almost eliminated when TROPOMI data acquired during the commissioning phase of its operation are excluded from the dataset (not shown here). This is in line with the work of  Inness et al. (2019)  that detected enhanced discrepancies between TROPOMI NRTI TOC and other sensors in the high northern latitudes for this particular time period, when a lot of in-flight calibration and testing took place. Unfortunately, the 6 % difference between the NRTI and OFFL products in this area (Fig. 7a ) is only reduced to 5 % when the same temporal restriction is applied. The inter-sensor consistency is very good for the time series of the Brewer and the SH Dobson comparisons (Fig.
The TOC datasets from the other sensors are restricted to the time period of the TROPOMI/S5P, namely from November 2017 to November 2018. Daily NRTI observations, as well as the corresponding GOME2A/2B data records, were averaged on 2. 5 • × 2. 5 • latitude-longitude grid, while the OFFL data, and corresponding GOME2A/2B and OMPS data records, were placed on a 0. 5 • × 1. 0 • grid. For each pair of instruments, daily gridded relative differences were then computed for every grid cell containing measurements and all those daily difference grids were then either averaged in time to have a global representation of the spatial patterns of the differences (as shown in Fig. 16 ) or also averaged in space for certain lat- itudes bands. As such, Fig. 17  shows the gridded differences as a monthly mean time series for selected zonal belts.
In the right column of Fig. 17 , the NRTI TOC product of TROPOMI is compared to GOME2A (Fig. 17b ) and GOME2B (Fig. 17d ) processed with the GDP 4. 8 algorithm. The percentage differences of the OFFL TOC compared to the other three sensors demonstrate great temporal stability for every latitude belt, except for the belt south of 50 • S (cyan line), where the variability is stronger. Those plots confirm the conclusions drawn previously, with differences generally lower than ±1 % at low latitudes and midlatitudes and slightly larger in polar regions. Recall also that the GOD-FIT v4 GOME2A and GOME2B datasets are produced with a Level 1b soft-calibration procedure, which introduces its own inaccuracies  (Lerot et al. , 2014). This might explain the slightly larger variability of the TROPOMI-GOME2A differences in the 50-90 • S bin and the larger TROPOMI-GOME2B differences in August 2018.
Acknowledgements. The authors acknowledge the financial support of the  European Space Agency "Preparation and Operations of the Mission Performance Centre (MPC)  for the Copernicus Sentinel-5 Precursor Satellite". The French scientists are grateful to  Centre National d'Etudes Spatiales (CNES)  and  Centre National de la Recherche Scientifique (CNRS)  for financial support. We warmly thank the  ESA Ozone Climate Change Initiative  project for pro-viding the GODFIT v4 datasets, the  EUMETSAT ACSAF  project for providing the GDP4. 8 datasets, the  Copernicus Services Data Hub  for providing the TROPOMI/S5P data on a timely manner, the  World Ozone and UV Data Centre  for providing the Brewer and Dobson spectrophotometer observations, the  European Cooperation in Science and Technology Action  ( COST Action   ES1207 ) for the Eubrewnet measurements and  Environment Climate Change Canada  for the Canadian Brewer observations.
Finally, we would like to acknowledge and warmly thank all the ground-based instrumentation investigators that provided data to these repositories on a regular manner, as well as the handlers of these databases for their upkeep and quality-guaranteed efforts. Financial support. This research has been supported by the  European Space Agency "Preparation and Operations of the Mission Performance Centre (MPC)  for the Copernicus Sentinel-5  Precursor Satellite " (contract no. 4000117151/16/1-LG ). Review statement. This paper was edited by  Ben Veihelmann  and reviewed by  Mark Weber  and one anonymous referee.
Data availability. The Level 2 TROPOMI TOC datasets are available at https://s5phub. copernicus. eu/ (last access: 6 September 2019) and https://s5pexp. copernicus. eu/ (last access: 6 September 2019) (TROPOMI OFFL TOC: https://doi. org/10. 5270/ S5P-fqouvyz, last access: 6 September 2019). The Brewer and Dobson daily datasets used in this work can be downloaded from the WOUDC database (http://www. woudc. org, last access: 6 September 2019; WMO/GAW Ozone Monitoring Community, 2017, https://doi. org/10. 14287/10000004, last access: 6 September 2019), while the individual Brewer measurements can be acquired by the Eubrewnet site (http://rbcce. aemet. es/eubrewnet/, last access: 6 September 2019; Rimmer et al. , 2018)  and the Canadian Brewer Network site (http://exp-studies. tor. ec. gc. ca/, last access: 6 September 2019).
The SAOZ GB data are available at the NDACC database (http://www. ndaccdemo. org/, last access: 6 September 2019) and from http://saoz. obs. uvsq. fr/ (last access: 6 September 2019)  (Pommereau and Goutail, 1988). Rapid delivery SAOZ data are available from the LATMOS real time (RT) facility at http://saoz. obs. uvsq. fr/ SAOZ-RT. html (last access: 6 September 2019) (Andrea Pazmino,  personal communication, 2018). The OMPS/NPP, GOME2/Metop-A and GOME2/Metop-B TOC data processed by the ESA's CCI GODFIT v4 algorithm were made available by Christophe Lerot (BIRA-IASB; personal communication, 2018; OMPS GODFIT v4: https://doi. org/10. 18758/71021044, last access: 6 September 2019). The GOME2/Metop-A and GOME2/Metop-B are processed by EUMETSAT's ACSAF GDP4. 8 algorithm and can be downloaded from https://acsaf.
Results PfpTKL transcript sequencing and protein annotation. To confirm PfpTKL transcription, we performed overlapping PCR on reverse transcribed Pf3D7 total RNA using primer pairs derived from the predicted PF3D7_1106800 sequence (Supplementary Fig. S1  and Table  S1 ). We analyzed 6-12 sequences amplified from two independent reverse transcribed RNA preparations for each of the eight transcript fragments (length 600-1200 bp). The deduced amino acid sequence (1483 residues) was compared to the PlasmoDB  43  predicted sequence. Both sets of data were identical with the exception of minor substitutions that did not affect the overall annotation (Supplementary Fig. S1 ). More detailed analysis revealed the presence of multiple domains (Figs 1 and 2; summarized in Table  1  and showed in Fig.
Sterile alpha motif (SAM) 299-364 (Fig. 2d ) SAMs belong to the alpha protein family (289 folds -SCOP database  113  ). They typically fold into 4-5 orthogonal α helices. They are involved in interactions with protein or RNA  71, 72. In the Plasmodium proteome: -there are four SAMs (PfpTKL, PfTKL1, PfTKL3, PF3D7_0926000)  66  -there are two SAM-like domains involved in interactions with RNA (prototypical HTH motifs) in Pfg27  114, 115. The PfpTKL SAM domain is predicted to fold classically (Fig. 2c ). The PfpTKL SAM core domain includes all SAM canonical residues (Fig. 2d ). The PfpTKL SAM domain is close to SAMs involved in proteinprotein interactions (Supplementary Fig. S5 ). This phylogenetic analysis includes Plasmodium SAM and SAM-like sequences as well as reference SAM and SAM-like sequences across the tree of life.
PbpTKL interactome in trophozoite-infected erythrocytes. To determine whether the exported PbpTKL interacts with erythrocyte proteins, we screened for interaction partners in trophozoite-infected mouse erythrocytes using anti-HA immunoprecipitation. We screened the total lysates of erythrocytes infected with a wild-type parental P. berghei line and ghost lysates of erythrocytes infected with the P. berghei line expressing PbpTKL-AID-HA. Proteins that remained bound to the anti-HA beads were analyzed by mass spectrometry, and those absent in the wild-type samples but present in at least two ghost samples from three experiments were selected. The resulting list of 23 mouse proteins (Fig. 7e ; Supplementary Table  S6 ) was assessed for cellular functions using the Uniprot database  53  , GO annotation and interactome data available in the STRING database  54.
berghei ANKA pG230 strain. Clones were confirmed by diagnostic PCR (Supplementary washes, proteins bound to beads were detected by western blot (right panel). (c,d) RVxF2 inhibits progesteroneinduced germinal vesicle breakdown (GVBD) in X. laevis oocytes. (c) Chart showing GVBD percentage over time in progesterone-incubated X. laevis oocytes micro-injected either with proteins or with control buffers (mean ± SD; three biological replicates and two technical replicates with 10 oocytes per data point). Oocyte images (external view and hemisections) are available for each sample in the Supplementary Information. ***, p < 0. 001. (d) GVBD of oocytes micro-injected with RVxF-containing proteins was assayed by analyzing XeCDC2 dephosphorylation and XeH3 phosphorylation by western blot. Only KD_RVxF2 (third lane) was able to block progesterone-induced XeH3 phosphorylation.
Three biological replicates were analyzed per sample type (raw and interactome mouse protein analysis data are available in Supplementary Table  S6 ). PbpTKL is dispensable for intra-erythrocytic cycle completion, gametocyte emergence and male gametocyte exflagellation. (a-e) Data collected using mice infected either with the wild-type PbGFP strain (parental) or the PbGEM-342364-transfected strain (pGEM) -10 6 parasites/mouse, seven mice per group. (a) Knocking out PbpTKL does not impact parasitemia. Parasitemia follow-up in mice infected either with the parental or pGEM P. berghei parasites (mean ± SD). (b) Knocking out PbpTKL does not improve mouse survival. Percent survival of mice infected with either parental or pGEM P. berghei parasites. (c) Knocking out PbpTKL does not affect gametocyte emergence.
S1  and Table  S1 ). Following the transformation of TOP10 bacteria and clone sequencing, 6-12 sequences per region were compiled into one consensus covering the whole PfpTKL transcript using SeqMan for comparison with PlasmoDB data  43. Protein annotation. The PfpTKL protein sequence was analyzed using SMART  77  , CATH  78  , Interpro  79  and ScanProsite  80. The tertiary structure was determined using the prediction tools Phyre2 Server 81 , M4T  82  and RAPTOR  83  (all well ranked by CAMEO  84, 85  ). RVxF motifs were identified based on two consensus sequences  86, 87  (Fig. 2b ) and the PlasmoDB Protein Motif Pattern tool. Low-complexity regions and putative post-translational modifications were predicted using ScanProsite  80. Signal peptides were predicted using SignalHmmS  88.
ns, no significant difference. For each phylogenetic analysis, sequences were aligned using MAFFT  89  (Supplementary Information) and evolutionary history was inferred using the maximum likelihood method based on the JTT matrix model in Molecular Evolutionary Genetics Analysis v6 (MEGA6)  90, 91. All positions with less than 80% site coverage were eliminated, leaving 598 positions in the final PfpTKL dataset and 64 in the final SAM dataset. The initial tree for the heuristic search was obtained by applying the neighbor-joining method to a matrix of pairwise distances estimated using a JTT model. For PfpTKL, a discrete gamma distribution was used to model evolutionary rate differences among sites. Evolutionary history was represented by the bootstrap consensus tree inferred from 1000 replicates  92.
Raw mass spectrometry data have been deposited in the ProteomeXchange Consortium via the PRIDE partner repository  101  with the dataset identifier PXD011986. The MS data files were processed using MaxQuant v1. 5. 8. 3 and searched using the Andromeda search engine against the Mus musculus database from Swissprot 07/2017 and Plasmodium berghei ANKA from PlasmoDB (v37). The PbpTKL-AID-HA chimeric protein sequence was also integrated. Parent mass and fragment ions were searched with initial mass deviations of 4. 5 and 20 ppm, respectively. The minimum peptide length was set to seven amino acids and strict specificity for trypsin cleavage was required, allowing up to two missed cleavage sites. Carbamidomethylation (Cys) was set as a fixed modification, whereas oxidation (Met) and N-terminal acetylation were set as variable modifications.
The false discovery rates (FDRs) at the protein and peptide level were set to 1%. Scores were calculated in MaxQuant as previously described  102. The reverse and common contaminant hits were removed from the MaxQuant output. Proteins were quantified according to the MaxQuant label-free quantitation (LFQ) algorithm  102, 103. Matches between runs were not allowed. Wild-type and PbpTKL-AID-HA IP biological replicates were analyzed using Perseus v1. 6. 2. 3. The LFQ data were log2 transformed and proteins identified in at least two of three PbpTKL-AID-HA replicates but never in the wild-type samples were considered "significant". The data were represented on a volcano plot following the imputation of missing values by creating a Gaussian distribution of random numbers with a standard deviation of 30% relative to the standard deviation of the measured values and a 4 (wild-type) or 1.
Figure8. PbpTKL is dispensable for intra-erythrocytic cycle completion, gametocyte emergence and male gametocyte exflagellation. (a-e) Data collected using mice infected either with the wild-type PbGFP strain (parental) or the PbGEM-342364-transfected strain (pGEM) -10 6 parasites/mouse, seven mice per group. (a) Knocking out PbpTKL does not impact parasitemia. Parasitemia follow-up in mice infected either with the parental or pGEM P. berghei parasites (mean ± SD). (b) Knocking out PbpTKL does not improve mouse survival. Percent survival of mice infected with either parental or pGEM P. berghei parasites. (c) Knocking out PbpTKL does not affect gametocyte emergence. Gametocytemia follow-up in mice infected with either with the parental or pGEM P. berghei parasites (mean ± SEM). (d) Knocking out PbpTKL does not affect male/female gametocyte ratio.
Paf1C stimulates heterochromatic histone turnover in G0 cells We previously showed that the turnover of histone H3 in heterochromatic regions of fission yeast is reduced in vegetative cells lacking the Leo1 subunit of Paf1C  [10]. To investigate whether histone turnover was Fig. 3  Loss of Leo1 leads to repressed transcription of genes located near the telomeres of chromosomes I and II. a The table shows the numbers of differentially regulated genes between leo1∆ and wild-type cells at each time point during quiescence. The R/Bioconductor package EdgeR was used for the analysis of differential gene expression. For a gene to be deemed significant, the FDR adjusted p value had to be less than 0. 05. 'Down' , 'Not changed' and 'Up' indicate genes downregulated, unchanged and upregulated, respectively, in leo1∆ cells relative to their expression in wild-type cells.
Propidium iodide (PI) staining and flow cytometry Cells grown in PMG or PMG-N medium were collected and fixed with 70% ethanol. Then, cells were washed with 50 mM sodium citrate (pH 7. 0) and treated with 240 µg/ ml RNase A in 50 mM sodium citrate (pH 7. 0) for 1 h at 37 °C. Cells were stained with 1. 25 µg/ml PI in 50 mM sodium citrate (pH 7. 0). Stained cells were imaged with a confocal microscope using the Cy5 channel. The DNA content was monitored using a FACSCalibur (Becton Dickinson). Data analysis was carried out with Cell Quest software.
Viability assay Viability assays were performed according to the protocol described in Joh et al. [6] , with minor modifications. A 1 ml aliquot of cell suspensions was taken from incubated cell cultures at the indicated time points and stained with Phloxin B (5 µg/ml final concentration) for 15 min. Cells were washed with 1 × phosphate-buffered saline (PBS) and imaged with an Axioplan 2 fluorescence microscope and ImageJ software using the FITC and DIC channels. A minimum of 400 cells was counted for each measurement using ImageJ software, and survival rates were calculated based on the number of dead (stained and green) cells divided by the total number of cells (green and stain-free) counted.
ChIP microarray For microarray hybridization, immunoprecipitated DNA was amplified as described by Durand-Dubief et al  [22]. Fragmentation, labeling and hybridization to the Affymetrix GeneChip S. pombe Tiling 1. 0FR were performed by the BEA core facility at Novum (http://www. bea. ki. se) according to Affymetrix standard protocols. For domainogram visualization, raw data from Affymetrix (. CEL format) were normalized using Affymetrix Tiling Analysis Software (TAS) v1. 1. Duplicate data were normalized to input using quantile normalization plus scaling using a bandwidth of 100. Data obtained from TAS were then directly loaded into the Seqmonk program, and the antibody background was removed using data for the clr4∆ mutant. Data were visualized using the following parameters: number of classes, 30; min probe count, 30; and max probe count, 100.
RNA-seq To remove rRNA, 4 µg of purified total RNA was treated with a ScriptSeq Complete Gold Kit (Yeast) (Epicentre). A total of 40 ng of rRNA-depleted stocks were used to generate sequencing libraries using a ScriptSeq v2 RNAseq Library Preparation Kit (Epicentre). Samples were quantified using a Qubit (HS dsDNA) and sequenced using an Illumina HiSeq 2000 platform (50 cycles, single-end sequencing) at the BEA facility (Huddinge, Sweden) following the manufacturer's instructions. The raw HiSeq data (fastq files) were aligned to ASM294v2 using Bowtie2 with the default parameters. The ASM294v2. 24 annotation was downloaded from pombase. org. The aligned data (SAM files) were imported and normalized per million reads. Data from independent biological duplicates were averaged. Identical reads were discarded to remove PCR artefacts.
Funding Work in the K. E. laboratory was supported by grants from the  Swedish Cancer Society  (C. F. ) and the  Swedish Research Council  (V. R. ). K. E. was the recipient of a Wenner-Gren stipend for a sabbatical stay at the  Pasteur Institute, France. E. O. was the recipient of a postdoctoral fellowship and travel support from the  JSPS Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers  ( S2704 ). Funding was provided by  Cancerfonden ,  Vetenskapsrådet ,  Wenner-Gren Foundation and Japan Society for the Promotion of Science.
Study design and interventions PRIMARYS was a prospective multicenter, open-label, singlearm phase IIIb study in which patients with GH-secreting pituitary macroadenomas received primary medical treatment with lanreotide autogel at a fixed dose of 120 mg every 4 weeks for 1 year  (14). Each pituitary MRI collected during the main PRIMARYS study (as previously described (  14 )) was re-read by a single neuroradiologist to determine T2 signal intensity and assess complementary information. The PRIMARYS study, from which this post hoc analysis is derived, is registered with EudraCT (EudraCT2007-000155-34) and ClinicalTrials. gov (NCT00690898). As previously described, patients provided written informed consent before study start, the trial was conducted with the Declaration of Helsinki, Good Clinical Practice guidelines and all local regulatory requirements before trial initiation, and the protocol, its amendments, consent form, study questionnaires and the patient information leaflet were approved by institutional review boards  (14).