dataesr/scientific-paragraphs-categorization huggingface dataset:
However, the ribbons and fibrils did not induce additional NF-κB nuclear translocation (Fig. 3a ) or trigger additional release of pro-inflammatory cytokines when treated in sequence with the TLR ligands compared to treatment with TLR ligands alone (Fig. 3b-i ). These data suggest that α-syn did not affect TLR ligand signalling in pericytes. Conditioned media collected from pericytes and microglia after 24 h of co-treatment of LPS with ribbons or fibrils showed no significant changes in the amount of pro-inflammatory cytokines released compared to LPS alone (Supplementary Figs. 7, 8 ). Microglia were included as a comparison for the inflammatory responses. The remaining results were only completed on pericytes. Pericytes take up and degrade α-synuclein. No endogenous α-syn was detected in the primary human brain pericytes in culture (Fig.
Images were acquired using the automated fluorescence microscope ImageXpress Micro XLS (Version 5. 3. 0. 1, Molecular Devices, CA, USA) using the 20× (0. 45 NA) CFI Super Plan Fluor ELWD ADM objective lens and Lumencor Spectra X configurable light engine source. Quantitative analysis of several measures including percentage positive cytoplasmic staining, cytoplasmic intensity measures and nuclear transcription factor location were performed using the cell scoring and integrated morphometry analysis modules on MetaXpress software (Version 5. 3. 0. 1, Molecular Devices, CA, USA). Roughly 500-1000 cells were scored per well with multiple wells (at least three) analysed per sample. Cytometric bead array analysis. Conditioned media samples from pericytes and microglia treated as above were spun at 200×g for 5 min and the supernatant collected and stored at -20 °C.
The concentration of cytokines was measured using a cytometric bead array (CBA) (BD Biosciences, CA, USA) as per manufacturer's instructions. CBA samples were run on an Acuri C6 flow cytometer (BD Biosciences, CA, USA). Data were analysed using FCAP-array software (version 3. 1; BD Biosciences, CA, USA) to convert fluorescent intensity values to concentrations using an 11-point standard curve (0-10,000 pg/mL) (Supplementary Table  4 ).
Quantitative analysis of several measures including percentage positive cytoplasmic staining, cytoplasmic intensity measures and granularity measurements were performed using the cell scoring, granularity and integrated morphometry analysis modules on MetaXpress software (Version 5. 3. 0. 1, Molecular Devices, CA, USA). Roughly 500-1000 cells were scored per well with multiple wells (at least three) analysed per sample. CellROX. Pericytes were either pre-treated with MG132 (5 µM) for 6 h prior to incubation with α-syn ribbons or fibrils for 24 h. CellROX reagent was added to the cells at a final concentration of 5 µM. The cells were subsequently incubated for 30 min at 37 °C. 5% CO 2. To label cell nuclei, the NucBlue Live Cell counterstain was added at the same time as the CellROX reagent.
The cells were subsequently imaged using the automated fluorescence microscope ImageXpress Micro XLS (Version 5. 3. 0. 1, Molecular Devices, CA, USA) using the 20× (0. 45 NA) CFI Super Plan Fluor ELWD ADM objective lens and Lumencor Spectra X configurable light engine source. Quantitative analysis of several measures including percentage positive cytoplasmic staining, cytoplasmic intensity measures and granularity measurements were performed using the cell scoring, granularity and integrated morphometry analysis modules on MetaXpress software (Version 5. 3. 0. 1, Molecular Devices, CA, USA). Roughly 500-1000 cells were scored per well with multiple wells (at least three) analysed per sample.
Statistical analysis. All experiments were performed in at least three independent cases. In general, data are presented as mean ± standard deviation (SD) from at least three independent experiments. Data visualization and statistical hypothesis testing was performed using GraphPad Prism Version 8. 02, Python 3. 9. 9 and the Seaborn 0. 11. 2 library. Two-way analysis of variance (ANOVA) was used when comparing time across the cytokine and inflammatory stimuli treatments with Tukey's multiple comparisons adjustment. One-way ANOVA with Tukey's multiple comparison adjustment was used when comparing responses between treatments. Statistical significance was set as p < 0. 05.
Acknowledgements The authors would like to acknowledge the generosity of the tissue donors and their families for their gifts of brain tissue for research. We also thank the  Hugh Green Biobank , the  Neurosurgical teams at Starship Children's Hospital and Auckland City Hospital  and all the technical staff involved at the  Neurological Foundation Human Brain Bank  in the collection and processing of the human brain tissue and cells at the  Centre for Brain Research. This work was supported by the  Michael J Fox Foundation , the  Hugh Green Foundation , the  Gillespie Neurological Foundation Postgraduate Scholarship , the  Brain Research New   Zealand Postgraduate Scholarship , the  Deane Endowment Trust, Centre for Brain Research (Ian and Sue Parton) , the  Health Research Council of New.
Funding This work was funded by  The Michael J. Fox Foundation for Parkinson's Research  (Grant ID  16420 ), the  Health Research Council of New Zealand  ( 3710464  and  3723033 ) and the  Centre National de la Recherche Scientifique  and the  EU joint Programme on Neurodegenerative Diseases  ( TransPathND ,  ANR-17-JPCD-0002-02  and  Protest-70 ,  ANR-17-JPCD-0005-01 ).
Introduction Primary production in high-latitude marine ecosystems is performed by eukaryotic phytoplankton. Among the latter are prasinophytes, a polyphyletic group of green algae containing nano-and pico-phytoplanktonic taxa (≤20 µm and ≤2 µm in cell diameter, respectively;  [1] ). A number of prasinophytes within the class Mamiellophyceae, including the picoplanktonic Micromonas and Bathycoccus, have been reported as major contributors to the overall phytoplankton community and biomass in a North Atlantic region influenced by subpolar water masses  [2]. Additionally, in the Arctic itself, culturing and PCR-based environmental surveys have exposed one particular Micromonas lineage  [3] , which is also abundant in Arctic sequence datasets  [4, 5]. This lineage was then observed in Antarctic waters based on metagenomic analyses  [6] , with a possible connection between poles via deep-ocean currents, and has now been described as a distinct species, named Micromonas polaris  [7].
Detailed information on the sediment trap collection, preservation, and sample preparation for DNA isolation can be found in  [24]  and https://doi. pangaea. de/10. 1594/PANGAEA. 845616 and https://doi. pangaea. de/10. 1594/PANGAEA. 855472 (both accessible as of 23 April 2022). Briefly, collection cups of 400 mL were filled with filtered seawater, adjusted to a salinity of 40 and spiked with mercury chloride at a final concentration of 0. 14% to preserve samples during the deployment and after recovery. Samples were then stored at 4 • C until the time of analysis; large zooplankton (>0. 5 mm) were removed under a dissecting microscope. Next, for the purpose of this study and flux calculations (see below), we used a split of the original sediment trap sample (ranging from 1/512 to 1/128, Supplementary Table  S1 ) that was filtered onto a 0.
Two-liter subsamples were taken in PVC bottles from the Niskins. Planktonic cells were collected by sequential filtration of one water sample through three different mesh sizes (10, 3, and 0. 4 µm) on 45-millimeter-diameter Isopore Membrane Filters at 200 mbar using a Millipore Sterifil filtration system (Millipore, Burlington, MA, USA). The Sterivex membranes were then stored at -20 • C until further processing. CTD data from depth profiles collected during the POLARSTERN cruise ARK-XXV/2  [25]  and other environmental metadata are accessible on PANGAEA. Sampling map was produced using Ocean Data View v5. 2. 1 (available online at: https://odv. awi. de accessible as of on 23 April 2022).
High-Throughput Sequencing and Analysis Amplicons were generated using the 16S rRNA V1-V2 primers 27F_ill (5 -TCGTCGGC AGCGTCAGATGTGTATAAGAGACAGagrgttygatymtggctcag-3) and 338R_ill (5 -GTCTCG TGGGCTCGGAGATGTGTATAAGAGACAGgcwgccwcccgtaggwgt-3 ; capital letters represent Illumina linker sequences on the 27F/338R primer pair) as in  [26]  and purification was performed using a MinElute kit (Qiagen, Hilden, Germany). Amplicon products were sequenced using the Illumina Miseq platform. Primer sequences were cropped out using CutAdapt software  [27]  to remove a fixed number of bases (-u parameter) matching the 27 F (20 bp) and 338 RPL (18 bp) primer lengths. Trimmed fastq files were quality-filtered, dereplicated, and merged with dada2 R package, version 1. 2  [28]. Potential chimeras were removed de novo using the removeBimeraDenovo command.
We used reference sequences assigned as stramenopile plastids in PR2 v4. 14. 0  [32]. Redundancy was removed from the PR2 database first, with clustering using CD-HIT v. 4. 6  [33]  at 99% nucleotide identity. This final processed PR2 database and resulting diatom reference tree contained a total of 832 sequences. Diatom amplicons from our study were then mapped onto the PR2 reference tree using EPA-ng, following the same procedures as in  [26]  to taxonomically identify amplicons.
polaris, rather than that of M. commoda-like strains. Our primer-probe sets did not distinguish between M. polaris and M. commoda-like species, potentially explaining why, overall, the correlation-based analyses of abundance versus temperature did not suggest coherent relationships. The peak Micromonas abundance observed was at station HGN-IV, at 18 m (5. 45 • C), with 5594 ± 444 18S rRNA gene copies per mL. We also quantified Micromonas 18S rRNA gene copies in the sediment trap and lander samples using qPCR. The data exhibited temporal variation, with higher Micromonas fluxes in summer traps (July-August) at 1250 m ("Mitte"), 2380 m ("Lander"), and 2495 m ("Unten"). Abundances peaked within each temporal monitoring during the second half of July at 1250 and 2495 m (236,823 ± 15,498 and 451,764 ± 20,732 gene copies per m 2 per day, respectively) and, during the 30 days of sampling between mid-July and mid-August, they peaked at 2380 m (418,763 ± 61,052 gene copies per m 2 per day) (Figure  3c ).
Altogether, a new generation of studies is needed that involves the time-series assessment of presence and abundance in water columns and sediment traps in the context of physical water masses, as well as their intermingling and movement. These studies will be needed in order to truly characterize pico-eukaryotic contributions to carbon export from surface to deep waters and the seafloor. Von Appen et al. (2021) emphasize that "As Arctic sea-ice melts, the biological carbon pump changes, impacting global climate and other critical ocean attributes (e. g. , biodiversity). " The Fram Strait encapsulates these types of change, with the modification in sea ice extent that has been developing for decades (i. e. , the decrease in sea ice thickness and increase in sea ice extent)  [62]. Because we collected data from various years in the warmer eastern part of the Fram Strait and along the Svalbard-Greenland transect, our quantitative assessments serve as an important initial set of baseline data for monitoring picophytoplanktonic community changes, both in the photic zone and in the material exported to the seafloor.
Supplementary Materials: The following supporting information can be downloaded at: https:// www. mdpi. com/article/10. 3390/microorganisms10050961/s1. Table  S1 : Moored sediment trap samples. Table  S2 : Seawater samples. Table  S3 : List of dominant diatom amplicons. Table  S3 : List of diatom Amplicon Sequence Variants (ASVs) representing >1% of stramenopile reads per sample with their corresponding sequences and taxonomic assignment using phylogenetic placement. Data Availability Statement: Detailed information on the sediment trap collection, preservation, and sample preparation for DNA isolation can be found at https://doi. pangaea. de/10. 1594/PANGAEA. 845616 and https://doi. pangaea. de/10. 1594/PANGAEA. 855472. Metadata on samples were extracted from PANGAEA websites. The amplicon sequencing data set generated for this study can be found in GenBank, under accession numbers SAMN27660762 to SAMN27660770.
Acknowledgments: We thank the captains and crews of the RV Polarstern for their excellent support during the expeditions  PS74 ,  76 ,  78 ,  80 ,  85 , and  93. We would like to thank the  AWI Deep Sea group  for scientific and technical support as well as the laboratory technicians and student helpers for helping with the sediment trap work and nucleic acid isolation. We thank  Sebastian Sudek  for support in the amplicon sequencing and qPCR.
Regarding the exploration, the task was designed to investigate whether participants were able to maintain the divergent QA skill that was trained in the previous space (i. e. agents' ability to transfer this skill). We also wanted to investigate if the question-asking skill helped them initiate and maintain autonomous explorations. Furthermore, the data collected in this space also serves us as a behavioral measure of epistemic curiosity. In fact, we use the idea developed in  [17]  where the authors measure curiosity as the individual's willingness to 'work' for information. Since we constraint children to think of divergent questions if they want to reveal new educational videos, these questions become the effort participants make when the only reward they get in return is the information (i.
Technical implementation The interface was programmed in JavaScript using the REACT library and was connected to a RESTful API to publish and retrieve the interaction data. As presented in the diagram below (Figure3), the behavior of the agent in terms of selection of the adequate cue(s) to offer was predefined and handscripted: it was connected to a database containing the different text resources and every text had a sequence of linguistic and semantic cues linked to it. Depending on the child's condition, the agent's automaton composes the dialogue utterances in order to include the appropriate support. We changed the utterances between the questions to avoid repetition in the agent's dialogue: a replica is not executed if it has been delivered during the previous question  [22]. We recruited 57 CM1 students belonging to four classes from two French primary schools, they were between 9 and 10.
Procedure The experiment consisted of four sessions of 1h15 within the same week: One for collecting the profile measures mentioned above, one for the divergent-QA training, one for the exploration and one for the post-intervention assessment. See study timeline in Figure  4  and details of the different measures in the data collection paragraph 4. 3. Our study was approved by the institute's ethics committee (certificate n°2019-23) and only started after having all participants parents' signed consents. Session 1 During the first session, we presented the study to the participants and collected the age and gender data. We also administered the questionnaires concerning the curiosity trait, the perception of curiosity and device use frequency. We then run the reading abilities test and the question-asking fluency test (see more details of the tests in the chapter 4.
Discussion In this work we investigate the efficiency of a conversational agent designed to foster curiosity-driven learning in children. For our data analysis, we rely on behavioral measures of epistemic curiosity such as the ability to generate divergent questions and to lead autonomous explorations. Our findings showed that our incentive agent was more successful in enhancing divergent questionasking abilities and transferring them to new contexts where no help/ cues are given to help participants. We could therefore argue that children of the experimental group were more able to maintain their performance level not only because the agent was successful in training the formulation of divergent questions but, even further, because it was successful in training their abilities to identify knowledge gaps while learning.
Background: Synovial sarcoma (SS) occurs in both adult and pediatric patients. The primary aim of this study is to describe the outcomes, prognostic factors, and treatment of patients with metastatic SS within a nationwide cohort. Patients and methods: All pediatric and adult patients with metastatic SS are registered in the French Sarcoma Group database. Data were collected from the national database https://conticabase. sarcomabcb. org/ up to March 2020. Descriptive and comparative analyses were conducted using SAS 9. 4 and Stata Special Edition 16. 1 software. Results: Between January 1981 and December 2019, 417 patients with metastatic SS from 17 French sarcoma centers were included, including 64 (15. 3%) under the age of 26 years. Median age was 42. 5 years (range 9-87 years). The metastases were synchronous (cohort 1) or metachronous (cohort 2) in 18.
INTRODUCTION Synovial sarcoma (SS) is a malignant mesenchymal tumor characterized by a specific t(X; 18) (p11. 2; ] [11]  In terms of prognosis, there are still questions regarding age and the specificities of SS,  6, [12] [13] [14] [15]  such as perioperative treatment. ] [18]  In this context, characterizing the natural history of SS is important, and requires larger series than those previously reported. The objective of 'METASYN', a retrospective study by the French Sarcoma Group (FSG), was to describe the management and outcomes of adult and pediatric patients with metastatic SS and included in the Conticabase database.
Patients Clinical data were collected from the Conticabase (https:// conticabase. sarcomabcb. org) and not from the NetSarc database, which was set up later. The study was first approved by the FSG, then declared to the Commission Nationale de l'Informatique et des Libertés (CNIL) on 18 July 2018, number 2203224, and approved by the ethics committee in Angers on 4 February 2020 (approval number 2020/10). All living patients received an information letter. Clinical data for the 417 patients were updated. Between July 1980 and April 2019, the sex, histology, grade, depth, size, location, treatment, relapse, and survival of the 417 adults, children, and adolescents and young adults (AYA, 15-25 years old) with treated metastatic SS were collected. Two cohorts of patients were created in 'METASYN': cohort 1 for patients with synchronous metastatic SS, and cohort 2 for patients with metachronous metastatic SS.
Statistical analysis All data were anonymized and analyzed retrospectively. Qualitative factors were described by the frequency of their respective modalities and compared using Pearson's chi-square test (or Fisher's exact test). Continuous factors were described by their mean AE standard deviation (or mediand interquartiledrange) and compared using Student's t-test (or the ManneWhitney/Wilcoxon test). The dose intensity of ifosfamide was calculated as the total dose received and the number of courses. Overall survival (OS) was defined as the time from the date of treatment of the first metastatic relapse to the date of death. Progression-free survival (PFS) was defined as the time from the start of the reporting periods to the date of progression (or the date of the next line or the date of death).
14, 20, 26, 27 The positive effect of time is that it is possible to make comparisons across periods in real life. 0, 21  The second criticism is that the FSG database includes data for all patients but because the size of the cohorts was too small between children and adults, the differences in clinical presentation could not be shown. In published series, mostly focused on patients with localized SS, no difference has been observed, even if a trend has been identified in the literature with a higher proportion of locations in the thigh, large invasive tumors, and an increased risk of synchronous metastases for AYA in comparison to children. 7, 26, 27  Third, and because of the retrospective nature of METASYN, caution is needed when evaluating the response rate as there was probably not always a RECIST reference or a centralized radiological review.
ACKNOWLEDGEMENTS GSF-GETO,  Net-SArc  and  RRePS. FUNDING None  declared. DISCLOSURE JYB: research support and honoraria from  Novartis , Glax-oSmithKline,  Bayer ,  Roche ,  Deciphera ,  Ignyta ,  Merck Sharp & Dohme (MSD) ,  Bristol Myers Squibb (BMS) ,  Pharmamar. OM: declares financial interests from  Bayer ,  Blueprint Medicines ,  BMS ,  Eli Lilly ,  Ipsen ,  MSD ,  Pfizer ,  Roche ,  Servier ,  Bayer. All other authors have declared no conflicts of interest. JYB holds grants from  NetSarc (INCA and DGOS)  and  RREPS (INCA & DGOS) ,  RESOS (INCA & DGOS) ,  LYRICAN (INCA-DGOS-INSERM 12563, Association DAM's, Eurosarc  ( FP7-278742 ),  Fondation ARC, Infosarcome ,  InterSARC (INCA) ,  LabEx DEvweCAN  ( ANR-10-LABX0061 ),  PIA Institut Convergence François Rabelais PLAsCAN  (PLASCAN,  17-CONV-0002 ),  La Ligue de L'Ain contre le Cancer, La Ligue contre le Cancer, EURACAN  ( EC 739521 ), and  RHU4   DEPGYN  ( ANR-18-RHUS-0009 ).
2C ), except that in the (ultrahigh-resolution) tazobactam cocrystal structure, Lys73, Ser130, and Asn132 could all be modeled in two conformations. In the major Ser130 conformer (occupancy, 0. 6; equivalent to the conformation Space group P2 1 2 1 2 1 P2 1 2 1 2 1 P2 1 2 1 2 1 P2 1 2 1 2 1 P2 1 2 1 2 1 P2 1 2 1 2 1 No. of molecules/Asymmetric unit (ASU) observed at full occupancy in the enmetazobactam cocrystal structure), the side chain is oriented away from Ser70/Lys73, an approximately 76°rotation compared to its position in the uncomplexed enzyme (PDB code 4HBT  [34] ). In the minor conformer (occupancy, 0. 4), the Ser130 side chain points toward Lys73 (Fig. 2D ). Further comparisons with uncomplexed CTX-M-15 show that cross-link formation elicits no significant change to the positioning of Glu166, the proposed general base for deacylation (4), or of the deacylating water molecule (Fig.
42 Å or 0. 91 Å, respectively (Table  1 ). Additional diffraction data collected for uncomplexed CTX-M-15 E166Q (Table  3 ) indicate that Asn170 adopts two conformations in the E166Q-substituted active site, with the conformation observed in the native enzyme being the minor conformer (occupancy, 0. 28) (Fig. S4 ). The major conformation (occupancy, 0. 72) is also observed in a P167S/E166A double mutant of CTX-M-14 (PDB code 5VTH  [35] ). Gln166 in apo-CTX-M-15 E166Q adopts the same orientation as Glu166, with other active-site residues also in equivalent positions (Fig. S4 ). Importantly, difference electron density maps from both the enmetazobactam and tazobactam cocrystals reveal the presence of a lysinoalanine cross-link between Ser70 and Lys73 (Fig. 4A  and B ). Lys73 in the CTX-M-15 E166Q :enmetazobactam cocrystal could be modeled in two conformations (occupancies, 0.
09 Å) which are suggestive of the imine form of tazobactam, as evidenced by the location of difference peaks consistent with the expected atom locations for a C = N bond (Fig. S9 ). However, despite the high quality of our data, we cannot rule out the possibility that the captured structure contains either the trans-enamine intermediate or a mixture/equilibrium of the imine/trans-enamine forms. The stability of different PAS-derived intermediates in the b-lactamase active site is likely enzyme and environment specific; Raman spectroscopy has shown the imine form to be the most stable in OXA-10 (  41 ) and the transenamine more stable in SHV-1  (16) , while in CTX-M-9 these intermediates can be readily attacked by Ser130 to form a b-alkoxyacrylate via a Ser70-Ser130 covalent bridge  (42). In a previously determined structure of tazobactam bound to the class A b-lactamase GES-2 (PDB code 3NIA  [30] ), the ring-opened PAS was covalently bound to Ser70, but at 1.