dataesr/scientific-paragraphs-categorization huggingface dataset:
These factors included STAT5 and, to a lesser extent, MAPK1/3. These proteins are key actors downstream of FLT3-internal tandem duplication (ITD) signaling in AML. Interestingly, MOLM-14 and MV4-11 cell lines, which harbor FLT3-ITD mutations, were the most sensitive to the antileukemic activity of VPS34-IN1, PIK-III, or Autophinib in our current experiments (Fig. 1A  and Supplemental Figs. 2A, 3B ). To confirm this increased sensitivity in FLT3 mutant AML cells to VPS34 inhibitors, we used BA/F3 cells which are IL-3-dependent for growth and survival. BA/F3 cells engineered to express the FLT3-ITD mutations showed an increased sensitivity to VPS34 inhibition compared to BA/F3 wild type (Fig. 5D  and Supplemental Fig. 7 ). Interestingly, using data from Beat AML project  36  , we observed that the expression of VPS34 was significantly increased in FLT3 mutant AML (Fig.
5E ). Altogether, these data suggest an elective VPS34 dependency in this sub-type of AML, and a role of VPS34 in FLT3 mutant signaling. We next tried to confirm the results of phosphoproteomic analysis. We observed that VPS34-IN1 strongly inhibited STAT5 phosphorylation in MOLM-14 and in (see figure on previous page) Fig. 4  VPS34-IN1 inhibits L-asparaginase induced autophagy and bot drugs act synergistically. A MOLM-14 cells were cultured for 6 h with Lasparaginase and/or chloroquine (10 µM) as indicated. Autophagy induction was assessed by analyzing both LC3-I and LC3-II expression by western blot. Upon autophagic induction, LC3-I is transformed to LC3-II which is then degraded in autophagolysosome. Chloroquine is able to inhibit acidification of autophagolysosome, allowing the evaluation of LC3-II formation which is an indirect marker of autophagy induction B Number of LC3B puncta per cells (right) and immunofluorescence analysis of GFP LC3 (left) in vehicle-treated or L-Asparaginase-treated (10 UI/ml) MOLM-14 cells were determined; n = 3, bars represent standard error of the mean.
C Percentage inhibition of phosphotyrosine in the 11 most downregulated proteins identified by phosphoproteomic analysis. D BA/F3 WT and BA/F3 cells with FLT3-ITD expression, with or without IL-3, were cultured for 48 h in the presence of VPS34-IN1 over a large concentration range. Viability was quantified using the fluorescence based Uptiblue assay; n = 3, bars represent standard error of the mean. E Comparison of VPS34 expression (normalized RPKM) in AML cells from patients with or without FLT3 mutation. Data are from Vizome database, a part of the Beat AML project  36. F MOLM-14 cells were cultured with vehicle or 5 µM VPS34-IN1 for 1 h. Western blotting was then used to analyze FLT3 expression, and STAT5 and P42/44MAPK phosphorylation. G Ba/F3 cells were cultured in the presence of IL-3 with vehicle or VPS34-IN1 (5 µM) for 3 h.
Acknowledgements This work was supported by grants from the  Ligue Contre le Cancer (Contrats de Labellisation   R14077KK  and  ELFUZ17337 ), from the  Fondation ARC  pour la recherche sur le cancer (RB, grant  n°DOC20170505807 ) and from the  Association Laurette Fugain. We thank  Alain Schmitt  and the  Cell Imagery Department of the Cochin Institute  for performing the transmission electron microscopy. We also thank the  CYBIO Department of the Cochin Institute  for the FCM analysis. We thank  Dr Stephane Manenti  ( Cancer Research Center of Toulouse, INSERM ) for providing the VPS34 ShRNA plasmid. We are also grateful to  Dr Marie-Laure Brandely-Piat  and the pharmacy department of  Cochin Hospital  for providing L-asparaginase.
The others, the bicolor damselfish (Stegastes partitus), cocoa damselfish (Stegastes variabilis) and beaugregory (Stegastes leucostictus) tend turf-algae to a lesser degree and display limited territoriality. As the most common intensive-farming species, the longfin damselfish was used in all experiments. Analytical software. Analyses were conducted using R  51. Generalized linear mixed models (GLMMs) were fitted with the lme4 package  52  and zero-inflated GLMMs were fitted with the glmmTMB package  53. The multinomial logistic regression model used for algal analysis was performed with the packages nnet 54 and effects  55. Associations between mysids and damselfish farms. To determine whether mysid swarms were associated with Stegastes farms, we conducted a series of transects. Thirty 30-m transects were laid haphazardly across the study site.
Acknowledgements This research was supported by a  National Geographic   Research grant  to  R. M. B. ( 9860-16 ). W. E. F. was supported by the  Alexander von Humboldt Foundation. We thank the  Government of Belize  for permission to conduct the study, and  D. Chivers ,  M. Ferrari ,  Z. Foltz ,  S. Alanko ,  J. Alanko ,  M. Lehmann , and  M. Ashur  for logistical assistance. Animal ethics were approved by the  University of Delaware  ( AUP 1300 ). We thank  W. Price  for assistance with mysid taxonomy and  D. Chivers ,  M. Ferrari ,  A. Brumm ,  A. Peel , and  M. Langley  for comments on the manuscript. This is contribution 1047 of the  Caribbean Coral Reef Ecosystems Program (CCRE) ,  Smithsonian Institution.
Data collection Pathological evaluation for IHC study We obtained the continuous value of percentage HR expression both in ER and PR. We defined ER as positive if ER expression by IHC was 1% or more. HER2 positivity was determined according to the ASCO/CAP guidelines at the time of pathological evaluation. We defined pCR as no invasive components in residual tumor in the primary site or axillary lymph nodes in the surgical specimen  [10].
GE evaluation and pathway analysis for GE study We examined GE differences between patients with HR+/HER2-IBC and HR+/HER2-non-IBC by featureby-feature linear mixture models and then fitting a betauniform mixture model to control for multiple testing  [11, 12]. The number of significant genes was counted for false discovery rates at 1%. We used the Affymetrix U133 annotation package hgu133a. db (Affymetrix, Santa Clara, CA, USA) to export gene symbols for 22,283 probes. We determined upregulation and downregulation by median value of gene expression. After identifying significantly upregulated/downregulated genes in IBC, we looked for enriched canonical pathways that included these genes by using ingenuity pathway analysis (QIAGEN, Germantown, MD, USA). Next, we investigated the relationship between these canonical pathways and the ER signaling pathway.
Methods The study (ClinicalTrials. gov Identifier NCT02759952) was conducted in accordance with the Declaration of Helsinki, with ap-proval from the ethics committee of the University of Tübingen. Written informed consent was obtained from all participants. Patients were recruited from the clinics for hereditary retinal degenerations at the Centre of Ophthalmology of the University of Tübingen and 12 collaborating European tertiary referral centers. Patient travel and accommodation costs were compensated.
1684C>T p. R562W Sothilingam Catalytic Damaging PM1; PM2; PM3; Pathogenic 0. 00001193 et al, 11 2015 d domain PS3 c. 1689C>A p. H563Q Birtel et al, 28 Catalytic Damaging PM1; PM2; PM3 Likely pathogenic 0. 000007954 2018 domain c. 1705C>A p. Q569K Dryja et al, 5 1999 Catalytic Damaging PM1; PM2; PM3 Likely pathogenic 0. 0001344 domain c. 1862T>G p. L621R This study Catalytic Damaging PM1; PM2; PM3 Likely pathogenic None domain c. 2053G>A p. V685M Corton et al, 29 Catalytic Damaging PM1; PM2; PM3; Pathogenic 0. 00004957 2010 domain PS3 Abbreviations: NA, not applicable; GAF, cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA; gnomAD, Genome Aggregation Database; PM, pathogenic, moderate; PP, pathogenic, supporting; PS, pathogenic, strong; PVS, pathogenic, very strong; VUS, variant of uncertain significance.
g. , built form, housing types), and methods of transportation in LMICs, there is a need for context-specific research in settings  [13]. Moreover, multicountry studies are important, as they provide a platform to investigate between-country differences utilizing standardized data. Given the previously limited literature and its focus on HIC utilizing small and potentially unrepresentative samples, the aim of this study was to assess the association between sedentary behavior and sarcopenia among adults aged ≥65 years from six LMICs (China, Ghana, India, Mexico, Russia, and South Africa) using nationally representative datasets. These countries broadly represent different geographical locations and levels of socio-economic and demographic transition.
The Survey Data from the Study on Global Ageing and Adult Health (SAGE) were analyzed. These data are publicly available  [14]. This survey was undertaken in China, Ghana, India, Mexico, Russia, and South Africa between 2007 and 2010. When the survey was conducted, and according to the World Bank classification, Ghana was the only low-income country, and China and India were lower middle-income countries. However, it should be noted that China became an upper middle-income country in 2010. All other countries were classed as upper middle-income. The survey protocol has been published in detail elsewhere  [15]. Briefly, a multistage, clustered sampling design method was employed in order to obtain nationally representative samples. Participants were aged ≥18 years and oversampling of those aged ≥50 years was employed.
A standard questionnaire was used by trained interviewers and face-to-face interviews were conducted. To ensure comparability between countries, standard translation procedures were undertaken. The survey response rates were: China, 93%; Ghana, 81%; India, 68%; Mexico, 53%; Russia, 83%; and South Africa, 75%. As reported by the United Nations Statistical Division, sampling weights were developed in order to adjust for population structure. Ethical approval was obtained from the WHO Ethical Review Committee and local ethics research review boards. Written informed consent was obtained from all participants. This present analyses utilized existing data that is publicly available online; thus, there are no ethical concerns in terms of its use for secondary data analysis.
Sarcopenia Following the criteria used in a previous publication using the same dataset  [16] , sarcopenia was defined as having low skeletal muscle mass (SMM) confirmed by lower skeletal mass index (SMI) and either a weak handgrip strength or a slow gait speed  [17]. Skeletal muscle mass (SMM) was calculated as the appendicular skeletal muscle mass (ASM) based on the equation proposed by Lee and colleagues: ASM = 0. 244 * weight + 7. 8 * height + 6. 6 * sex-0. 098 * age + race-3. 3 (where female = 0 and male = 1; race = 0 (White and Hispanic), race = 1. 9 (Black) and race = -1. 6 (Asian))  [18]. Utilizing measured weight and height to create a skeletal muscle mass index (SMI), the ASM was further divided by BMI  [19]. Low SMM was defined as the lowest quintile of the SMI based on sex-stratified values.
However, it should be noted here that previous studies show a slightly higher risk between sedentary time and sarcopenia. This slight difference in findings may be owing to previous work consisting of small and potentially unrepresentative samples and solely focusing on HICs. The present findings add to this literature by showing that such an association exists in a large sample of both men and women from LMICs using nationally representative datasets. Considering sarcopenia has been shown to be associated with premature mortality, disability, falls, and lower quality of life  [3, 4] , the present finding that a one-hour increase in sedentary behavior per day was associated with 1. 06 times higher odds for sarcopenia is meaningful, and sedentary behaviour reduction interventions may provide another avenue to prevent against sarcopenia.
Funding: This paper uses data from  WHO's Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the  U. S. National Institute on Aging through Interagency Agreements   OGHA 04034785 ,  YA1323-08-CN-0020 ,  Y1-AG-1005-01  and through research grants  R01-AG034479  and  R21-AG034263.
MBE Anchors must be provided for each pair of synteny blocks issued from a comparison G/H. We recall that synteny blocks handled by PhyChro can overlap and that the same gene can be an anchor for distinct blocks. Duplicated synteny blocks are treated as independent blocks even though their anchors can be shared. PhyChro accepts synteny blocks that are reconstructed with various tools as long as they are converted into the expected format, described in the README file of the PhyChro package. For the applications to yeast and vertebrate species, synteny blocks were computed with the SynChro software  (Drillon et al. 2014) , setting the D parameter to 3. D is a parameter that allows to define synteny blocks by controlling the complexity of internal microrearrangements. Intuitively, high values of D are more permissive and allow larger microrearrangements to be tolerated within synteny blocks, whereas smaller values of D are more stringent and split synteny blocks at microrearrangement breakpoints.
This implies that, for distantly related genomes, increasing the D value allows to recover a larger number of synteny blocks. For these genomes, small values of D would allow recovering the signal only from small inversions. Notice that when PhyChro reconstructs trees using blocks computed with D ¼ 2, the yeast tree contains three erroneous splits and the vertebrate tree contains 1, whereas both trees are correct when blocks are computed with D ¼ 3 or 4. SynChro automatically reconstructs pairwise synteny blocks that can be directly read by PhyChro, and it can be downloaded at www. lcqb. upmc. fr/CHROnicle/SynChro. html. To analyze how sensitive is PhyChro to synteny block reconstruction, we constructed a second set of synteny blocks with the program i-ADHoRe 3. 0  (Proost et al. 2012). We followed the protocol used in  (Drillon et al.
2014 ) fixing parameters as follows: prob. cutoff ¼ 0. 001, gap_size ¼ 15, cluster. gap ¼ 20, q_value ¼ 0. 9, and anchor. points ¼ 3. The remaining parameters were set with default values. The i-ADHoRe 3. 0 software package is available at bioinformatics. psb. ugent. be/software. PhyChro was tested on 13 vertebrate species and 21 yeast species. About three more vertebrate species were used to discuss difficult vertebrate positioning and the possible contribution of PhyChro in these analyses. The detailed list is given in the supplementary table  S1 , Supplementary Material online. The vertebrate genome sequences have been downloaded from NCBI and the yeast species were downloaded from several sites listed in supplementary table  S2 , Supplementary Material online. Duplicated Genes, Duplicated Anchors, and Duplicated Blocks PhyChro does not directly work with genes except while identifying adjacencies found in genomes G, H within a third genome K.
By doing it, it considers only genes that are defined as "anchors" (defined in section "Synteny Blocks"-Materials and Methods, point 1). In this respect, PhyChro requires synteny blocks to be provided as input together with the set of their anchor genes. PhyChro constructed the vertebrate and yeasts phylogenies based on Synchro, a program identifying synteny blocks by reciprocal best hits (RBH)  (Drillon et al. 2014 ). The RBH condition searches for the best bidirectional matching pairs of genes in G and H and creates a one-to-one map. This means that if G has two copies g 1 and g 2 of a gene, the RBH condition does not allow to map both g 1 and g 2 in G to the same gene in H. It is important to notice that this definition does not prevent to have two copies B 1 and B 2 of a block in G that are mapped into the same block in H.
PhyChro Computational Time PhyChro time complexity depends on the number of genomes given in input and on the number of rearrangements that took place among these genomes. Phylogenetic reconstructions with PhyChro were tested using one thread on a single machine equipped with an Intel Xeon E5-2670 CPU, running at 2. 60 GHz with 132 GB of RAM and a Linux operating system (CentOS release 6. 5). PhyChro ran in 13 and 19 min for the 13 vertebrate and 21 yeast species, respectively. A total of  130,485 and 179,649 breakpoints, of 75,675 and 108,935 synteny blocks, and of 17,848 (1,501 different ones)  and 20,924 (3,901) partial splits were identified for vertebrate and yeast genomes, respectively. Clearly, the reported time Phylogenetic Reconstruction Based on Rearrangements. doi:10. 1093/molbev/msaa114.
Phylogenetic Reconstructions Based on Protein Sequences We identified 357 families of syntenic homologs (considered as orthologs) sharing >90% of similarity between the 13 vertebrate species, and 80 families sharing >80% of similarity between the 21 yeast species, using SynChro  (Drillon et al. 2014). Orthologous proteins were aligned with MUSCLE (version 3. 8. 31) (Edgar 2004 ) and alignments were cleaned with Gblocks (version 0. 91 b)  (Castresana 2000). Cleaned concatenated alignments were then provided to PhyML 3. 0 (which was run with the LG amino acid substitution model) and ProtPars. For Neighbor, we computed the distance matrix using ProtDist and ran it with the neighbor-joining option. ProtPars, Neighbor, and ProtDist are included in the PHYLogeny Inference Package (version 3. 67)  (Felsenstein 1989 ) and have been used online at mobyle.
Acknowledgments We thank  Ingrid Lafontaine  for critical reading of the article. This work was supported by the  Agence Nationale de la Recherche  (" GB-3G ,"  ANR-10-BLAN-1606-01 ) (G. F. ), an  ATIP-Avenir Plus grant  from the  CNRS  (G. F. ), a teaching assistantship (ATER) from the  Ministere de l'Enseignement Sup erieure et de la Recherche  (G. D. ), the  Institut Universitaire de France  (A. C. ).
Search strategy of publications on transdisciplinarity in agroecology A query search was built to identify the relevant studies in agroecology from European scholars in agroecology claiming transdisciplinarity. From the bibliographic database of Elsevier's SCOPUS, we extracted publications that contained as the main search in the title, key words and abstract the word agroecology (or agro-ecology), which was bounded by 26 European countries (see Supplement 1 for details on the query). To grasp transdisciplinarity in its diversity, we designed a lexical query supported by an analysis of core papers in the domain. The query finally contains words related to transdisciplinarity or to multi/interdisciplinarity associated to participatory methods, stakeholder involvement or system approaches (see Supplement 1 for details).
Definition of problems How and who formulates the research problem Knowledge gap: The research aims to answer a knowledge gap that has been previously recognized in the scientific arena. Social living issue: The research recognizes an issue that has an impact on society and which contribution could help solve or visualize the situation. To construct the typology of transdisciplinarity practices in agroecology, a Hierarchical Clustering on Principal Components (HCPC) was conducted using the FactoMiner R package  (Husson et al. 2011). HCPC is a Multiple Correspondence Analysis (MCA) followed by an Ascending Hierarchical Clustering (AHC) on the MCA results. We used the eight active variables presented in Figure  1  and, extra supplementary variables to enrich the analysis (i. e. time frame to develop the research, agroecological conception, type of research approach, country of authors, continent where the research occurred).
Type of research approach and participation of stakeholders From the content analysis of 389 articles (Figure  1  Corpus B), we identified that authors adopted thirteen different research approaches: i) field studies, ii) field experiments, iii) field studies and site measurements, iv) method proposition, v) reflexive analysis, vi) field studies and laboratory analysis, vii) comparative studies, viii) future scenarios, ix) field experiments and laboratory analysis, x) models xi) meta-analysis, xii) review and xiii) theoretical. The more theoretical studies (Reviews, meta-analysis and theoretical), represent 38% of the publications (n= 148). However, a citation analysis of 405 articles (see corpus A in Figure  1 ), using the VOSviewer software (van Eck and Waltman 2017), shows a low citation level of reflexive work on transdisciplinarity.
Typology of transdisciplinary practices in agroecology After an overview of the main characteristics on the way European agroecologists deal with transdisciplinarity, we here focus on the way researchers implemented it. Based on a restricted corpus of 68 articles (Figure  1  Corpus C), we built a typology described into two sections. The first one outlines the variables that characterize transdisciplinary in practice as they are synthetized with a MCA. The second section describes a typology of approaches based on clusters derived from the HCPC and crossed with the opinions of the interviewees. The MCA (Figure  6a-b ) allowed to determine the importance of the variables that mainly characterize transdisciplinarity in agroecology. The first plan represents 42% of the total dataset inertia, in which the first dimension (30.
The resulting maps consisted of 14 641 single diffractograms each. For the side view measurements, the diffractograms were recorded using an Eiger X 4M detector (Dectris Ltd. , Baden-Daetwill, Switzerland) at a distance of 203. 5 mm to the sample. To minimize scattering by air molecules, the distance between the sample and the detector was bridged by a helium-filled flight-tube. The wavelength of the X-ray beam was 0. 847 Å. The beam was focused to a size of ≈150 × 150 µm 2. The scanning grid step size was set to 200 nm and X-ray exposure time per step was 0. 5 s. Images were taken at significant steps of attachment and detachment of the seta. Data Analysis: The data analysis and calibration were performed using the Python software library pyFAI for fast azimuthal integration. After background subtraction, each diffractogram from the 2D scans was evaluated regarding wide-angle XRD, SAXS intensity, or SAXS intensity and orientation.
Acknowledgements S. F. and C. F. S. contributed equally to this work. The authors acknowledge the  European Synchrotron Radiation Facility  for provision of synchrotron radiation facilities at beamline ID13. The authors thank  Prof. Friedrich G. Barth  and  Wolfgang Kallina  from the  Department of Neurobiology of the University of Vienna, Austria , for the supply of living spiders. This study was supported by the  German Science Foundation  grant  DFG-GO 995/38-1  to  S. N. G. Open  access funding enabled and organized by Projekt DEAL.
Diffraction Data Collection and Structure Determination Diffraction data were collected at the MX-beamline 14. 1 at the BESSY II electron storage ring (HZB, Berlin, Germany)  [39]. The diffraction data were processed using XDS as implemented in the XDSAPP package  [40]. The DHS crystal structures were solved by molecular replacement with Phaser  [41]  using 1DHS as a search model. The obtained models were rebuilt using Coot  [42]  and refined using Phenix  [43]. During the refinement, ~1. 5% of the reflections were used for cross-validation analysis to monitor the refinement strategy. Water molecules were automatically placed during structure refinement, or further added using Coot and subsequently manually inspected. The quality of the model was validated using MolProbity and PDB REDO  [44]  servers.
FRET Measurements To investigate the DHS affinity to polyamine, a FRET experiment relying on the energy transfer from DHS W327 to the dihydronicotinamide ring of NADH was performed, as described previously  [25]. Briefly, 5 µM of DHS wt was incubated in the presence of 10 µM NAD in 100 mM Tris-Bicine pH = 8. 5 buffer, and sequentially, 2 uL of 50 µM SPD or 1 mM SPM were added to reaction mixture. After the addition of each substrate portion, the fluorescence signal (λex = 295 nm, λem = 441 nm) was recorded until saturation was achieved. Apparent K D values were calculated using the Hill model implemented in Graphpad Prism 8 (GraphPad Software, Inc. , California, USA).