dataesr/scientific-paragraphs-categorization huggingface dataset:
After cell fixation-permeabilization in 75% ethanol/PBS-incorporated Edu was labelled and detected with the Click-iT EdU Alexa Fluor 488 Flow Cytometry Assay Kit (Invitrogen). Analyses were done on a FC500 Beckman Coulter Flow Cytometer. Alexa Fluor 488conjugated EdU-positive cells were quantified using the Flow Jo analysis software (Treestar).
Statistical analysis. A linear mixed-regression model, containing both fixed and random effects, was used to determine the relationship between tumour growth and number of days after grafting. BLI data were first transformed using the natural log scale to better fit the assumptions of the linear mixed model. The fixed part of the model included variables corresponding to the number of post-graft days and the different treatments. Interaction terms were built into the model; random intercepts and random slopes were included to take time into account. The coefficients of the model were estimated by maximum likelihood and considered significant at the 0. 05 level. Statistical analysis was performed using the STATA 10. 0 software (Stata Corp. , College Station, TX, USA). Clinical samples. We have recovered from public database transcriptome data of the cetuximab-treated patient's cohort of Khambata-Ford data set, (GSE5851;  Khambata-Ford et al, 2007)  that includes gene-expression data from 80 patients with mCRC enroled for treatment with cetuximab monotherapy.
To address the clinical relevance of p38 activation in the response to cetuximab treatment, FOXO3a and p38 mRNA expression levels were analysed in a transcriptome data set created by  Khambata-Ford et al (2007) , (GSE5851) from 80 patients with mCRC and treated with cetuximab monotherapy. Among patients with mCRC harbouring WT KRAS (n ¼ 43), FOXO3a and p38 expression were higher in cetuximab responders (n ¼ 20) than in non-responders (n ¼ 19; P ¼ 0. 009 for FOXO3a and P ¼ 0. 04 for p38; Figure  6A ). This is in agreement with our in vitro and in vivo results showing that FOXO3a and p38 are required for cetuximab full activity. Recently, different CRC molecular subtypes have been defined based on the combined analysis of their gene-expression profile  (Schlicker et al, 2012; Budinska et al, 2013; De Sousa et al, 2013; Marisa et al, 2013; Sadanandam et al, 2013; Roepman et al, 2014).
The association between CRC molecular subtypes and response to cetuximab has been evaluated using the Sadanandam and De Sousa E Melo's classifications  (De Sousa et al, 2013; Sadanandam et al, 2013)  and the Marisa's classification by our group (Del Rio et al, manuscript submitted). We found that in the 43 patients with mCRC harbouring WT KRAS from the Khambata-Ford data set, patients with a cancer classified as C1 or C5 (Marisa's subtypes) had a significantly longer progression-free survival than patients with other subtypes (Del rio et al, manuscript submitted). Similarly, the Sadanandam's TA subtype was associated with a better response to cetuximab  (Sadanandam et al, 2013)  and De Sousa E Melo's CCS1 subtype with better disease control rate  (De Sousa et al, 2013). Here, we analysed FOXO3a and p38 geneexpression level in the different CRC molecular subtypes and found the highest expressions in the C1, C5 (P ¼ 8.
ACKNOWLEDGEMENTS We thank the  Montpellier RIO Imaging  facility for flow cytometry experiments, in particular Nadia Vie. The Supplementary Figure 1 was generated using the Servier medical art (www. servier. fr). This work was supported by  INSERM  and  ICM Val D'Aurelle. LM had a PhD studentship from the  French government. EC has a PhD studentship from the  Labex MabImprove. AT had a MabImprove post-doctoral fellowship. The research leading to this publication was funded by the  French National Research Agency  under the  programme 'Investissements d'avenir' Grant Agreement LabEx MAbImprove :  ANR-10-LABX-53  and  SIRIC (INCA-DGOS-Inserm 6045 ). This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.
6 clones, respectively, BD Pharmingen). Acquisition was performed on a LSR II cytometer with FACSDiva software (version 6. 1, BD Biosciences, Le Pont au Claix, France). Murine BMDCs were generated as described previously. 16 Briefly, bone marrow cells were extracted from FVIII exon 16 knock-out C57BL/6 mice and cultured in Petri dishes (2. 10 6 cells/10 ml/plate) for 10 days in RPMI-1640 supplemented with 10% fetal calf serum, 50 mM 2-mercaptoethanol and 200 U/ml murine recombinant GM-CSF (Cellgenix Technology Transfer, Freiburg, Germany). Supplemented medium was replaced at days 3, 6 and 8. BMDCs purity and phenotype were validated by the expression of CD11c (HL3 clone, BD Pharmingen).
Titration of anti-FVIII IgG and FVIII inhibitors ELISA plates were coated with FVIII (1 μg/ml, Recombinate®, Baxter, Maurepas, France), in bicarbonate buffer pH 9. 5, overnight Figure  2. Characterization of FVIII containing alanine substitutions of the residues predicted to interact with BO2C11. Panel A. B domain-deleted wild-type FVIII (FVI-II HSQ ), FVIII R2215A or FVIII R2220A were serially diluted 2-fold starting at 1 nM. Factor Xa generation was measured using a FVIII chromogenic assay. The reaction was stopped at 10 min using 20% acetic acid and the final absorbance measured at 405 nm. The data are represented as factor Xa generated in arbitrary units and are equivalent to the absorbance at 405 nm. VWF (Panel B), BO2C11 (human anti-C2 domain antibody, Panel C), ESH8 (mouse anti-C2 domain antibody that does not compete with BO2C11, Panel D), BO2BII (human anti-A2 domain antibody, Panel E) and KM33 (human anti-C1 domain antibody, Panel F) were immobilized on microtiter plates.
In vivo clearance of wild-type and mutated FVIII FVIII exon 16 knock-out mice and VWF/FVIII exon 16 double knock-out C57Bl/6 mice were injected intravenously with wildtype and mutated FVIII (10 nM in 100 μl). Blood was collected in 0. 129 M sodium citrate at different time points after FVIII administration. FVIII residual levels in mouse plasma were determined by sandwich ELISA using ESH8 and biotinylated GMA-8015 as capture and detection antibodies, as described above. Data are plotted as a percentage of the initial FVIII level, measured 5 min-utes after FVIII infusion, versus time (mean±SEM). Values at 5 min post-injection did not differ between the groups of mice treated with the different FVIII. Experimental data was fitted with a onephase exponential decay equation using GraphPad Prism software (version 6.
We also used data from three Estonian lakes where optical measurements are carried out in semi-regular basis. These lakes are Lake Peipsi, the fourth largest lake in Europe (3555 km 2 ), Lake Võrtsjärv (270. 7 km 2 ) and Lake Harku (1. 64 km 2 ). All the other lakes, besides Mälaren, are shallow (maximum depth between 2. 5 m and 12. 9 m, Mälaren 61 m).
Field Measurements Field measurements were carried out during three years 2011-2013. The total number of sampling stations was 105. The extreme CDOM-rich lakes Mustjärv and Nohipalu Mustjärv were sampled once, Meelva twice. Data from the other boreal lakes was collected in the frame of different projects. Lake Mälaren in Sweden was sampled once (7 sampling stations) while three Estonian lakes were studied almost on the monthly bases during three ice free seasons. We sampled Lake Võrtsjärv 9 times (19 samples in total), Lake Harku 11 times (one station each time), and Lake Peipsi 11 times (65 samples in total). Water reflectance measurements were carried out using two Ramses (TriOS) sensors one measuring downwelling irradiance and one measuring upwelling radiance from the nadir. Ramses In order to test how similar/dissimilar from remote sensing point of view are these extreme lakes from typical boreal lakes we chose other four lakes in Sweden and Estonia.
Lake Mälaren is the third largest lake in Sweden (1140 km 2 ). It is a gemorphologically sophisticated lake where different basins are often connected only through narrow straits. Optical properties of these basins vary in a wide range  [17, 21, 22]  and can be considered as different water bodies from an optical point of view. We also used data from three Estonian lakes where optical measurements are carried out in semi-regular basis. These lakes are Lake Peipsi, the fourth largest lake in Europe (3555 km 2 ), Lake Võrtsjärv (270. 7 km 2 ) and Lake Harku (1. 64 km 2 ). All the other lakes, besides Mälaren, are shallow (maximum depth between 2. 5 m and 12. 9 m, Mälaren 61 m).
Field Measurements Field measurements were carried out during three years 2011-2013. The total number of sampling stations was 105. The extreme CDOM-rich lakes Mustjärv and Nohipalu Mustjärv were sampled once, Meelva twice. Data from the other boreal lakes was collected in the frame of different projects. Lake Mälaren in Sweden was sampled once (7 sampling stations) while three Estonian lakes were studied almost on the monthly bases during three ice free seasons. We sampled Lake Võrtsjärv 9 times (19 samples in total), Lake Harku 11 times (one station each time), and Lake Peipsi 11 times (65 samples in total). Water reflectance measurements were carried out using two Ramses (TriOS) sensors one measuring downwelling irradiance and one measuring upwelling radiance from the nadir. Ramses is sampling with 3.
Satellite Data Suitability of Sentinel-2 and Landsat 8 was tested in two ways. First, we simulated theoretical performance of the satellites in the black lakes by recalculating Ramses field reflectance spectra using spectral response functions of the two satellites. Secondly, we used a Landsat 8 image from 8 July 2013 acquired simultaneously with our field campaign in Lake Peipsi and 1-2 days before sampling on the black lakes and Lake Võrtsjärv. Atmospheric correction was performed with four different methods from which ATCOR23 was selected as the best performing method for most of the lakes  [27]. More detail about the field campaign and different atmospheric correction methods tested is provided in  [27]. Sentinel-2 imagery was collected in 11 and 14 August 2015 and processed with SNAP Sentinel-2 toolbox and Sen2Cor atmospheric correction module provided together with the Sentinel Toolbox.
Acknowledgments: Fieldwork and data analysis costs were covered by  Estonian Science Foundation  Grants  8576  and  8654 ,  KESTA program  project  VeeObs ,  Estonian Basic Science Research  Grant  SF0180009s11 , and  FP7  project  eratH2Observe. Lake Mälaren data collection and analysis costs were covered by the  FORMAS  project "The Colour of water-interplay with climate, and effects on drinking water supply".
On these occasions, human samples were identified by name, age and household number and subsequently coded for the purposes of record-keeping. The process for collection and storage of faecal samples was consistent with that described by  Ash et al. (2015). During the two year study period, the average village population of 300 inhabitants was distributed across 55 permanent households. From these, 50/55 (90. 9%) households had at least one member that was (i) eligible for treatment at either MDA1 and/or MDA2 and (ii) supplied researchers with a faecal sample at the pre and/or post data collection events. Due to its higher sensitivity  (Praet et al. , 2013) , copro-antigen ELISAwhich identifies products released by adult Taenia species (Allan and Craig 2006)was chosen over standard microscopy techniques as the primary method for detection of Taenia species in these samples.
Statistical analysis Data were entered into Microsoft Excel and statistical analysis was carried out using the 'R' environment for statistical computing (R Development Core  Team, 2005). The function 'epi. conf' in the package 'EpiR'  (Stevenson et al. , 2013)  was used to provide confidence intervals for all prevalence and incidence estimates, accounting for the potential intra-household clustered nature of the data and the finite nature of the population under study, which remained relatively stable at approximately 300 persons throughout the study period. An estimate was made of the intraclass correlation coefficient using the ICCbare function in package ICC  (Wolak et al. , 2012)  and design effect then estimated as design = ICC*(n -1) + 1 where n = average samples per household. The copro-antigen ELISA used for human taeniasis detection has an estimated sensitivity of 84.
5% (95% C. I. 61. 9-98%) and specificity of 92% (95% C. I. 90-93. 8%) (Praet et al. , 2013). In order to incorporate these estimated parameters into the prevalence estimates, the 'epi. prev' function in package 'epiR' was used  (Stevenson et al. , 2013). Population impact was estimated with all participants in each sampling point used as the denominator (ie n = 121; n = 138), and individual level impact was estimated using only those participants who provided two sequential faecal samples as a denominator  (n = 48). Comparison between pre and post intervention prevalence levels was made using the 'chisq. test' function in 'epiR' at the village level and using the 'mcnemar. test' function for individual level data.
Community-level pre and post intervention prevalences Prior to the intervention, copro-Ag ELISA detected 37 cases of taeniasis (37/121) across 26 households (Fig. 2 ); a crude prevalence of 30. 6%. Accounting for the clustered nature of the data, and the finite population of approximately 300 people, resulted in a 95% confidence interval of 25. 5-38. 9%. Further adjustment for the sensitivity and specificity of the diagnostic assay resulted in the true pre-intervention prevalence estimate of 29. 5% (95% C. I 19. 7-40. 9%). Of the 37 positive copro-antigen ELISA samples, microscopy analysis detected taeniid eggs in 10 samples, which were subsequently submitted to PCR and sequencing. Of these, 8 matched published sequences to T. solium [NCBI Accession numbers AB086256 and L49444], with the remaining 2 identifying as T.
Acknowledgements The SPSP human and animal health component wish to thank their project counterparts from the  Centre for International Agriculture in the Tropics (CIAT)  and the  Lao PDR National Agricultural and Forestry Research Institute (NAFRI)  for their assistance during the pig interventions. The team also wish to thank the Lao PDR national WHO office for their overall support, as well as the  Lao PDR Department for Communicable Disease Control (DCDC)  for their facilitation and assistance in the human MDA interventions. In particular, the project team would like to thank the staff from the provincial and district  Ministry of Health offices  for their care and support in building community rapport during the project lifetime, and finally the community themselves for their hospitality, cooperation and trust.
Statistical analysis Descriptive statistics used included the mean (SD) as appropriate for continuous variables, and frequency (percentage) for categorical variables. Univariate analysis used included the chisquare or Fisher's exact test as appropriate to compare categorical variables and the nonparametric Mann-Whitney test to compare continuous variables. Multivariate analyses were performed with logistic regression. Efficacy was reported by treatment period. Statistical analyses were performed using EpiData TM (EpiData Software version 2. 0, "The EpiData Association" Odense, Danemark).
Results Characterization and sequence analysis of Plasmodium putative pantothenate kinase genes PanK1 and PanK2. The availability of genome sequence data from different species of malaria parasites made it possible to use sequences of bacterial, fungal, plant and mammalian CoA biosynthesis enzymes to search for their counterparts in the Plasmodium genome databases. All eukaryotic-type homologues of the enzymes of CoA biosynthesis have been identified in all Plasmodium species sequenced so far (http://mpmp. huji. ac. il/maps/ coasynthesis. html). One Plasmodium homologue was identified for PPCS, PPCDC, PPAT and DPCK but two homologues were identified for Pantothenate kinase (PanK) (Fig. 1A ). To date, biochemical characterization of the malarial pantothenate kinase activity has been determined only from parasite extracts.
Collectively, these data indicate that the genes involved in CoA biosynthesis are co-regulated, at least at the transcriptional level, by a mechanism that is involving PanK1 and PanK2 expression. Parasites lacking PyPanK1 or PyPanK2 undergo normal sexual differentiation but cannot complete their development in the mosquito. The viability of Pypank1(-) and Pypank2(-) parasites in mouse erythrocytes made it possible to assess the function of PyPanK1 and PyPanK2 in gametocyte development as well as in gametogenesis. Outbred SW mice were IV infected with 10 6 Pypank1(-), Pypank2(-), Pyp230p(-) or PyWT infected red blood cells and blood samples were collected and analyzed at day 3 post-infection to determine the number of male and female gametocytes and male gametes. No significant differences in the number of male or female gametocytes (P ~ 0.
Acknowledgements We thank  Lauren Lawres ,  Emma Fritzen  and  Fleur Porter  for the technical assistance with some of the experiments. AA is supported by funds provided by  Tulane University School of Public Health and Tropical Medicine  and by  NIH-NIAID  grant ( 1R21AI111058-01A1 ). CBM is supported by  NIH  grants ( AI097218 ,  GM110506 ,  AI09486  and  AI112938 ) and the  Bill and Melinda Gates Foundation  (ID#:  1021571 ).
We next analyzed the level of GLUT-1 and cyclin D1, two well-established specific target proteins of HIF-2α in VHL-defective ccRCC. 40, 41 Under normoxia and hypoxia, SphK1 silencing significantly reduced levels of both glucose transporter GLUT-1 (Figure  3b ) and cyclin D1 (Figure  3c ) in both cell lines. Cyclin D1 is an important regulator of cell-cycle progression, and in vitro and in vivo data have demonstrated that HIF-2α-only-expressing ccRCC cells proliferate faster than their HIF-2α and HIF-1α co-expressing counterparts. 42, 43 Therefore, we next assessed cell proliferation in SphK1-silenced VHL-defective ccRCC cells. [ 3 H]Thymidine incorporation assay clearly showed that SphK1-silenced A498 and 786-O cells proliferated much slower than their siScr-silenced counterparts (Figure  3d , left) and showed a survival disadvantage (Figure  3d , right) in both normoxia and hypoxia in line with the findings that HIF-2α likely contributes to tumor cell survival.
CONFLICT OF INTEREST Authors would like to disclose that Dr Sabbadini is a founder of Lpath, and has stock in the company and is an inventor. LIGUE to SP and Allocation de thèse PB and DM), Fondation de France (to OC), the Labex TOUCAN (to SP), the Comité 31 of the Ligue Contre le Cancer (to IA), Université Paul Sabatier de Toulouse (to IA), Allocation de thèse from the Fondation pour la Recherche Médicale (to CG and DM), Allocation de 4ème année de thèse from the Fondation ARC (to CG) and Bourse Angiogenèse from Roche (to OC). YM was a recipient of a post-doctoral fellow from Fondation de France and from Investissements d'Avenir (PHUC-CAPTOR).
Materials Input data were obtained from 172 patients aged between 19 and 55 years (mean age of 32 years with the standard deviation of 9. 4 years), including 67% of men. The study was conducted within routine tests performed in patients treated surgically in Centro Grandi Apparecchiature, Seconda Università di Napoli, Napels, Italy. All the patients were informed about the study, which was conducted in accordance with the Declaration of Helsinki. The measurements were made using the Pentacam HR keratometer with 1-19r11 software version (Fig. 1  shows examples of the results obtained) before refractive surgery, 1 month after the surgery and 3 months later. The following characteristics were measured: gender-feature w(1), age-feature w(2), left/right eye-feature w(3), cornea front/back-features w(4) and w  (5)  as the mean values of measurements for the angle of 90° and 180°, tangential anterior/posterior-features w(6) and w  (7) , analogously the mean values for the measurement in 4 points (similarly for the other features), net power of the cornea-feature w(8), total corneal refractive power-w(9), equiv K-reading power-feature w  (10).
qRT-PCR was performed using Power SYBR green PCR master mix on a 7300 real-time PCR system (Applied Biosystems) as described previously  (19). The levels of virB, icsA, and lacZ transcripts were analyzed using the 2Ϫ ⌬⌬CT (cycle threshhold [C T ]) method  (40) , and results are reported that the fold increase relative to the reference. Primers for mdh (endogenous control) and for virB, icsA, and lacZ transcripts were designed by using Primer Express software v2. 0 and validated. The following oligonucleotides were used (see Table  S1  in the supplemental material): mdhQF/mdhQR, virBQF/virBQR, icsAQL/icsAQR, and lacZQF/lacZQR. Primer extensions. Total RNA from exponentially growing plasmidcarrying E. coli strains was extracted  (41). Total RNA (10 to 20 g) was hybridized with 5=-32 P-labeled ML-512 and ML-1314 primers.
ACKNOWLEDGMENTS We thank  Davide Roncarati  for advice on DNaseI footprinting. We also thank  Gioacchino Micheli  and  Mikael Sellin  for critical reading of the manuscript. This work was supported by grants from  Sapienza University ,  PRIN2012-WWJSX8K  and  PTR 24-2016  (B. C. and G. P. ) and from the  Swedish Research Council  (E. G. H. W. ).
FUNDING INFORMATION This work was funded by grants from Sapienza University, from PRIN2012-WWJSX8K and from Institut Pasteur PTR-24-2016 to B. C. and G. P. , and from the Swedish Research Council to E. G. H. W. This work, including the efforts of Maria Letizia Di Martino, was supported by grants from Sapienza University, from PRIN2012-WWJSX8K, from Istituto Pasteur Italia, and from the Swedish Research Council. This work, and the efforts of Cédric Romilly, was supported by the Swedish Research Council.
Operant self-administration of alcohol After 5 weeks of the intermittent access (IA) to 20% alcohol, 2BC paradigm (IA20%-2BC), rats were trained to self-administer alcohol. The self-administration chambers (Med-Associates) contain two levers: an active lever (the alcohol lever), for which presses result in the delivery of 0. 1 ml of the alcohol solution (v/v), and an inactive lever, for which presses are counted but no alcohol solution is delivered. Rats were trained under a fixed ratio 3 schedule; i. e. , rats had to press three times to receive one reward. Sessions lasted for the duration of 1 h at the beginning of the training and 30 min after the first 2 weeks. The number of presses on the levers and the number of alcohol deliveries were recorded using MED-PC IV software (Med-Associates).
Data analysis Data are expressed as mean Ϯ SEM. Biochemical data were analyzed with a two-tailed unpaired t test. Behavioral data were analyzed with a twotailed paired or unpaired t test or by one-or two-way ANOVA with or without repeated measures (RM), depending on the experiment, followed by the Student-Newman-Keuls (SNK) test when indicated by significant effects of treatments or interactions. Statistical significance was set at p Ͻ 0. 05.
2F ; t (14) ϭ 1. 96, p ϭ 0. 07), and after 24 h of withdrawal (Fig. 2H ; t (14) ϭ 0. 56, p ϭ 0. 58) compared to control animals that consumed water only. Finally, we measured the levels of TrkB phosphorylation as well as the phosphorylation of ERK1/2 in total homogenate and found that neither TrkB nor ERK1/2 were phosphorylated, and thus activated, in response to binge alcohol drinking (p-TrkB, t (7) ϭ 1. 23, p ϭ 0. 26, n ϭ 4 -5/ group; p-ERK1/2, t (15) ϭ 1. 20, p ϭ 0. 24, n ϭ 8 -9) or after 24 h of withdrawal (p-TrkB, t (6) ϭ 0. 42, p ϭ 0. 21, n ϭ 4/group; p-ERK1/2, t (12) ϭ 1. 65, p ϭ 0. 13, n ϭ 7/group; data not shown). Together, these data suggest that long-term excessive drinking and withdrawal do not alter the expression or activity of TrkB. Next, we examined whether a history of excessive alcohol intake alters the levels and or localization of the low-affinity neurotrophin receptor p75NTR.