dataesr/scientific-paragraphs-categorization huggingface dataset:
This study has limitations. We included data from 10 CF centers from different countries with likely heterogeneous diagnostic and treatment regimens possibly introducing bias. For these reasons, all statistical models were adjusted for study center as random intercept. The models incorporate the fact that measurements from the same center are not independent, but more similar to each other by assigning an individual intercept for each center. This way, CF care centers with systematically biased values (e. g. , clearly above or below the average) should not substantially change the overall results. A priori, we included data from patients for whom follow-up information on survival and LTx was available greater than or equal to 5 years after CPET. Thus, patients who left their respective center shortly after the CPET were excluded already when the data were collected.
The data used for this study were gathered retrospectively. Thus, we had to limit the variables used as predictors of prognosis to those that were commonly assessed during the years 2000-2007. Because, for example, colonization with mycobacteria other than tuberculosis or  x Difference between cluster 3 and 4. jj Difference between cluster 1 and 2. ¶ Difference between cluster 1 and 3. **Differences between clusters based on chi-square statistics (P = 0. 039). If chi-square statistics are calculated for patients with known genotype by excluding patients with at least one "unknown; nonavailable" CFTR allele, no difference in genotype is observed between the groups (P = 0. 338). B. cepacia complex was not vigorously assessed at that time, such information could not be included in the models.
Finally, our data were collected before initiation of CFTR modulator therapies. Because these drugs may impact on lung function and overall survival, the predictors should be reevaluated in the context of highly effective CFTR modulators that may become available to most patients with CF in the upcoming years. Because aerobic fitness and ventilatory efficiency measured during CPET are related to prognosis, it is important to show whether improvements in these measures would translate into increased survival. Several randomized controlled trials have shown that exercise capacity can be increased in CF by exercise conditioning programs  (23). However, no conditioning studies with survival/mortality being the primary outcome are available to date. Because information from exercise testing in CF is relevant to patient care in several aspects, such as detecting adverse reactions to exercise, understanding exercise limitations, guiding a conditioning program, or motivating people to engage in strenuous physical activities, an increasing number of centers are including formal exercise testing in their routine work-up of patients with CF.
In vitro chemoresistance assay Primary cells were maintained in a humidified atmosphere with 5% CO 2 at 37 °C. MLLr-B-ALL primary samples cells were cultured in StemSpam medium (Stem Cell Technologies, Vancouver, BC, Canada) supplemented with stem cell factor, FLT3 ligand, interleukin-3 (IL-3) and IL-7 (all from PeproTech, Rocky Hill, NJ, USA) as described  [24]. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) were obtained, grown, and characterized as extensively described by our group  [25] [26] [27]. A total of 1 × 10 5 MLLr-B-ALL blasts were co-cultured in a 96-well plate with/without 2 × 10 4 irradiated BM-MSCs for either 30 min or 24 h. Cells were then exposed to 0. 5 or 50 µM VxL for 40 h. Viability (apoptosis) of CD19 + B-ALL blasts was measured using 7-AAD on a FACSCanto-II cytometer running FACSDiva software (BD Biosciences) as previously described  [28].
After repeated washing in PBS (3 × 2 h) slices were incubated with a secondary antibody cocktail solution (Jackson ImmunoResearch (Cambridge, UK and Invitrogen) including 2 µm 4′,6-diamidino-2-phenylindole (DAPI) for an additional 72 h at 4 °C. After successive washing steps, immunostained slices were optically cleared through overnight incubation in RapiClear 1. 52 (Sunjinlab, Hsinchu City, Taiwan). The slices were then mounted on glass slides for imaging using a SP8 Leica confocal microscope equipped with hybrid detectors using ×10 (HCX-PL-FLUOTAR) and ×20 (HC-PL-APO-CS2) objectives. Imaging data were analyzed and videos assembled using the Imaris v8. 2 software (Bitplane AG). Supplemental videos may be found in Supplementary data available with the online version of this article.
Statistical analysis Data are expressed as mean ± SEM of independent experiments unless otherwise specified. Statistical comparisons were performed using either paired or unpaired Student's t test, as appropriate. For MRD studies, data are expressed as median (range) and significant differences were analyzed by the median test. CRRs were statistically compared using Pearson's χ 2 test and EFS curves were compared using the log-rank test. Analyses were performed using GraphPad Prism v6. 0 (GraphPad Software Inc. , La Jolla, CA, USA) or SPSS software (SPSS version 22, Chicago, IL, USA). Statistical significance was defined as a p value < 0. 05.
v. transplantation (12 ± 1. 7% vs. <2%, p < 0. 001) (Fig. 1a , right panel). Importantly, clinical data from MLLr-BCP-ALL infants (n = 55) uniformly enrolled in the Interfant treatment protocol reveals that patients with refractory or relapsed disease initially had at diagnosis 28% more NG2-expressing blasts than those patients not experiencing relapse (53% vs. 41%, p > 0. 05). This suggests that NG2 plays a role in vivo in the propagation of MLLr-B-ALL cells. We then assessed in vitro and in vivo whether anti-NG2 (7. 1 MoAb) effectively eliminates NG2 + MLLr-B-ALL blasts. In vitro, anti-NG2 treatment was unable to activate effector mechanisms including CDC (Fig. 2a, b ) and ADCC (Fig. 2c ), resulting in no cytotoxicity of NG2-expressing MLLr-B-ALL cells in 4-and 24-h assays. As a control, Rituximab (anti-CD20 MoAb) effectively activated both CDC and ADCC cytotoxicity mechanisms to eliminate Daudi cells (Fig.
Acknowledgements This work has been supported by the  European Research Council  (CoG-2014-646903 and PoC-2018-811220), the  Spanish Ministry of Economy-Competitiveness  ( SAF2016 ), and the  Catalunya Government  ( SGR330  and  PERIS 2017 ) to PM, and the  Asociación Española Contra el Cáncer (AECC) ,  Beca FERO , and the  ISCIII/FEDER  ( PI17/01028 ) to CB RT-R, and OM are supported by postdoctoral fellowships from the  AECC scientific foundation  and the  Catalunya Government (Beatriu de Pinos ,  BP00048 ), respectively. PM also acknowledges the financial support from the  Obra Social La Caixa-Fundaciò Josep Carreras and "Premio Miguelín ". PM is investigator of the Spanish Cell Therapy cooperative network (TERCEL).
Virtual EDA helps to identify peaks that covary with observed biological effects, suggesting these as candidate causative chemicals (Fig. 3 ). Obviously, this approach does not directly provide cause-effect relationships, but allows hypothesis generation, which must be confirmed using, e. g. , literature and database review, calculation of toxic units using quantitative structure activity relationships (QSAR), or a full chemical and effect assessment with reference standards. Successful vEDA generally requires that: 1. The observed effect is caused by a limited (small) number of toxicants among those present in the samples.
Bioanalytical data from samples and fractioned subsamples studied to establish concentration-effect relationships; 3. In situ functional responses, comparatively assessed at potentially polluted sites and reference situations; and 4. Surveys on species and trait abundance as well as population and community structure (biodiversity) at potentially impacted sites and reference sites. This approach provides an adaptive and integrative method that systematically synthesizes the evidence from the different LOEs and provides optimum decision support for an ecologically oriented water management. The overall status of each of the four individual LOEs is condensed and categorized into classes that indicate clear or moderate signals of pollution-driven impacts (Fig. 7 ). In an application example, data obtained for the single LOEs from the 3rd Joint Danube Survey were analyzed  [6].
Mechanistic information for different action by pollutants is conserved by differentiation among the LOEs for the different biological quality elements Given the technological accomplishment made with the joint efforts of the SOLUTIONS consortium and other efforts in the last years, it is now possible to consider mixture occurrence and mixture toxicity in aquatic organisms and ecosystems. The real impact on improving water quality will ultimately be measured by policy uptake for amending monitoring demands in a revised Water Framework Directive. We believe that more balanced generation and utilization of exposure and effect data helps to foster evidencebased water quality assessments. Moreover, we are convinced that such an improved knowledge base will help to (i) develop more streamlined approaches to link chemical and ecological status monitoring and (ii) focus resources on major management tasks.
A gas phase takes a longer time to detach and produce fewer circulating bubbles during the decompression time. This would explain the lower levels of VGE observed in fit divers. Metabolism therefore introduces fitness as a second individual characteristic for a diver involved in a decompression. The action of age and fitness are opposed and independent but can combine in each diver to produce variability. On one hand, an old and sedentary diver should have larger volume of initial SMB than a young and fit diver and produce more VGE. On the other hand, an old but fit diver could produce less VGE than a younger but sedentary diver. In a recent large-scale database analysis, DAN Europe  (Cialoni et al. , 2017)  concluded that only two factors, increased age and BMI, could be related to increased bubble formation.
, 2016b). Figure  2  shows VGE counts from this last paper, expressed in number of bubbles detected per heartbeat, at rest and after a leg flexion, for the control dives and the dives with pre-conditioning with vibrations and oxygen. The protocol of VGE detections, with either Doppler or echocardiography, includes first a measurement at rest and then a measurement after a squat or leg flexions. The flexion generally triggers a rush of circulating bubble provoked by the muscular contractions. Referring to our model, it suggests that this flexion causes SMB to be dislodged from their sites before reaching the critical volume of detachment. Data in Figure  2  shows that there is no significant difference between rest and flexion after vibration and oxygen preconditioning. For the vibration preconditioning, the explanation could be that SMB have already been dislodged before the dive, so the muscle contraction applies to a smaller number of SMB and produces less VGE  (Germonpre and Balestra, 2017).
The BET specific surface area was calculated from the nitrogen adsorption data in the relative pressure range from 0. 05 to 0. 30. Transmission electron microscopy (TEM) characterisations were carried out with a JEOL2100 microscope coupled with an Energy Dispersive X-ray Spectroscopy (EDXS) device (JEOL, Tokyo, Japan) and operating at 200 kV. The samples were prepared by crushing the powders in an agate mortar. Then they were put in suspension in a drop of water that was deposited on a copper grid covered by a holey carbon film. Heating with light made the water evaporate and the powder stick to the grid. The surface of raw and functionalised ZrC were analysed by X-ray photoelectron spectroscopy (XPS, Kratos Axis Ultra DLD spectrometer), using a monochromatic AlKα source (15 mA, 15 kV). All binding energy scales were charge referenced to the C 1s peak (285.
In this way, the hydroxyl groups of the surface  [13, 14] , were used to functionalise the ceramic with an excess of ACDMS, at temperatures from 40 to 120 °C (Figure  1 ). To understand the microstructure of the bare and modified ZrC particles, and to prove the presence of the carbosilane on the surface, XPS, TG-MS and TEM coupled with EDX analyses were performed. First of all, the survey XPS spectra of every sample were recorded (Figure  2 ). From XPS data it was observed that the bare ZrC sample surface contained a significant amount of oxygen in addition to carbon and zirconium. This was due to the existence of an external smooth and continuous oxycarbide layer with a thickness of roughly 3 nm, as estimated thanks to higher magnification TEM images (Figure  3a ). After their surface was treated with ACDMS, silicon element signals emerged from the spectra (Figure  2 ).
Diffracting crystals were obtained in 0. 2 M ammonium sulfate, 0. 1 M sodium acetate pH 4. 6, 12% (w/w) PEG 4000 in batch wells containing 1 μL of the sample with 1 μL of crystallization solution covered by paratone and kept at 4 °C. Crystals were cryoprotected by transfer to the reservoir solution supplemented with 35% sucrose and flash frozen in liquid nitrogen. X-ray diffraction data were collected at beamline PROXIMA 2 A (SOLEIL synchrotron) and processed and scaled with the aP_scale module in autoPROC (Global Phasing Limited)  35  , using STARANISO to apply anisotropic correction to the data  36. MglA mixed form: A unique crystal was obtained with MglA-GTPγS using a sparse matrix screen (Classics suite, Qiagen) in 0. 1 M HEPES pH 7. 5 and 70% MPD, by hanging drops dispensed with a Cartesian crystallization robot.
MglA-GTPγS/MglB complex: The complex was prepared by incubating equimolar amounts of MglA and MglB with a 20× molar excess of GTPγS for 30 min at room temperature followed by purification by size exclusion chromatography using a Superdex 75 column and concentration at 20 mg/mL with a 5× molar excess of GTPγS. Initial crystallization conditions were obtained with the Protein Complex Suite (Qiagen) screened by sitting drop-vapor diffusion at 18 °C using a Mosquito robot and were optimized in hanging drops by mixing 1 μL of the sample with 1 μL of the precipitant. Diffracting crystals grew in 0. 2 M HEPES pH 7 and 16% PEG 4000. Crystals were cryoprotected by transfer to a solution containing 0. 2 M HEPES pH 7 and 35% PEG 4000 and flash frozen in liquid nitrogen. X-ray diffraction data were collected at beamline ID30-B at the European Synchrotron Radiation Facility (Grenoble, France).
thermophilus MglB as a search model. Alternatively, we used both crystals forms for molecular replacement with AMoRe 40 followed by density modification  41, 42. First, molecular replacement was carried out with monoclinic (P2 1 ) data (form 1, 15-4 Å) by using a monomeric multiple model (nine superimposed structures of T thermophilus MglB monomers from PDB entries 1J3W, 3T1R, 3T1S with pruned side-chains) and by applying rotational noncrystallographic symmetry (NCS) constraints based on self-rotation function peaks. The four monomeric models placed in the P2 1 asymmetric unit appeared in an arrangement similar to the tetrameric structure of T. thermophilus MglB, though with imperfect 222 symmetry. Successive density modification including fourfold NCS averaging and solvent flattening and phase extension to 3.
Crystallographic statistics are given in Supplementary Table  1. Structural data have been deposited with the Protein Data Bank with accession codes given in Table  1. Nucleotide exchange and GAP kinetics assays. Nucleotide exchange kinetics were measured by monitoring the decrease in fluorescence following mant-GDP dissociation and replacement by GTP added in fivefold molar excess (λ Ex = 360 nm, λ Em = 440 nm). GAP kinetics were measured by fluorescence, using an engineered bacterial phosphate-binding protein (PBP) (kind gift of Martin Webb, UK) to detect inorganic phosphate produced by GTP hydrolysis (λ Ex = 430 nm, λ Em = 465 nm)  25. After expression and purification, PBP was labeled with N-[2-(1-maleimidyl)ethyl]-7-(diethylamino)coumarin-3-carboxamide (MDCC). GAP experiments were performed at 25 °C using 5 μM (Fig.
3a, b ) or 10 µM (Fig. 3c, d  Frames corresponding to the high-intensity fractions of the peak and having constant radius of gyration (R g ) were averaged. All SAXS data analyses were performed with programs from the ATSAS package  45. R g was evaluated using the data within the range of Guinier approximation sR g < 1. 3 and by the Guinier Wizard and Distance Distribution Wizard. The maximum distance D max was estimated with PRIMUS and refined by trial and error with GNOM. The distance distribution functions P (r) were calculated with GNOM. The dimensionless Kratky plot was calculated by plotting (qR g ) 2 I (q) /I (0) against qR g. The molecular weight was estimated by PRIMUS Molecular Weight wizard. The fit between scattering experimental amplitudes and amplitudes calculated from the crystal structure of the MglB dimer was calculated with CRYSOL.
Ten independent ab initio models were calculated with GASBOR, using data at q = 0. 25 and imposing P2 symmetry, which were compared with SUPCOMB and clustered with DAMCLUST. The consensus model was represented by the lowest Normalized Spatial Discrepancy (NSD), which was determined with DAMSEL. The flexible Cterminal fragments in each MglB monomer were modeled with MultiFoXS  46. The resulting models were clustered into four ensembles, yielding an excellent fit to the experimental SAXS data. The SAXS data have been deposited with the SAXSDB database under the accession code SASDET9. SAXS statistics are given in Supplementary Table  2. Liposome cosedimentation. All lipids are natural lipids from Avanti Polar Lipids. Liposomes were prepared with 76% phosphatidylethanolamine (PE), 4. 9% phosphatidylglycerol (PG), 9.
After two washings of 5 min with Tris-buffered saline (pH 7. 6), 0. 2% Tween 20 membrane were incubated with Goat Anti-Rabbit IgG (H + L)-HRP Conjugate (#1706515, Biorad, dilution 1:10000) in the respective blocking buffers. The peroxidase reaction was developed by chemiluminescence (SuperSignal™ West Pico Chemiluminescent Substrate #34080 Thermo Scientific™) scanned and analyzed with ImageQuant LAS 4000 and TL analysis software (GE Healthcare Life Sciences). Reporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this article. supervised the study. C. G. , T. M. and J. C. wrote the manuscript with input from all authors.
Acknowledgements This work was supported by grants from the  ANR  to J. C. and T. M. ( ANR-15-CE13-0006 ) and to J. C. ( ANR-14-CE09-0028 ). We are grateful to  Armelle Vigouroux  ( LEBS, CNRS, Gif-sur-Yvette ) for preliminary crystallization experiments, and  Michel Franco  ( IPMC, CNRS, Sophia-Antipolis ) for suggesting the liposome composition. We thank the scientific staff at X-ray crystallography beamlines  PROXIMA1  and  PROXIMA 2  and SAXS beamline SWING (SOLEIL synchrotron, Gif-sur-Yvette, France) and X-ray crystallography beamline ID-29 ( ESRF synchrotron, Grenoble, France ) for making the beamlines available to us and for expert advice.
ACKNOWLEDGEMENTS C. Nouvel  and  L. M Forero Ramirez  acknowledge support from  ANR   JCJC ANR-12-JS08-0003-01  NANOCAPDEX for funding and PhD Research Fellowship, respectively. The authors express their highest gratitude to  Olivier Fabre  for NMR analyzes, to  Marie-Christine Grassiot  for help in SEC measurements andto  Isabelle Fries  for cytotoxicity assays.
Data The data used in this study come from both the ENOE and the INEGI. This study used panel data from the metropolitan areas of self-represented cities from 2005 to 2018. It uses the first trimester of each year of the ENOE, because in this trimester extended INEGI survey results are presented. The economic sectors include the manufacturing industry, the rest of the secondary sector (extractive industries, electricity, and construction), the high-tertiary sector (commerce, dining, accommodation services, transport, communications, mail and storage, professional, financial, and corporate services), and the low-service sector (social services, diverse services, government, and international organizations). The main variables are men's and women's average hourly incomes and full workday. Additionally, following the methodology of  Mora (2012) , the precariousness index includes (i) the employed population that has no social benefits, (ii) those earning equal or less than two minimum wages, and (iii) those without labor or non-union contracts.
Data was obtained from the ENOE. The precariousness index was developed based on the proportions of the population with these given characteristics. It is important to note that the Cronbach's Alpha test, which measures the internal consistency of a composite index  (Mora 2012) , was used to construct this index. 3  In addition, the construction of the wage gap variable was made via a methodology in which the income differential by gender uses the natural logarithm of labor 4 : Δμ y ¼ ln Y h -ln Y m ¼ ln ðY h =Y m Þ , between men (h) and women (m) (Mendoza-González et al. 2017), in the same way, we treated the exogenous variables. The output shows that the average income of men is higher than that of women. Multiplying this result by 100 provides a percentage.
The endogenous variable is the natural logarithm of labor income: ln ðY h =Y m Þ, just like the exogenous variables. The first endogenous variable measures the labor gap per hour each week between men and women who work full time  (Mendoza-González et al. 2017). In this model, y t is an NTx1 vector of the dependent variable; β is a coefficient, and ε t is an error term. The model in this study uses spatial panel data. It consists of 32 cross-sectional elements (metropolitan areas) and 13 cases from 2005 to 2018. Thus, the number of observations equals 32 × 13 = 416. It is important to highlight that the variables were generated with microdata from the ENOE: labor income, years of schooling, years of experience, hours of training, and labor participation are averages per metropolitan area; while variables such as the precariousness index (social benefits, wages equal to or less than two minimum wages, and non-labor and non-union contracts) as well as primary, secondary, and tertiary education were calculated, as was the employed population (or proportion) with the same characteristics, by metropolitan area.
Temperature ramp tests were carried out between 25 °C and 60 °C at 5% strain and 5 Hz to analyze the effect of temperature. A total of 3 mL of hexadecan were poured onto the samples before each analysis to avoid water and acetic acid evaporations. Viscosity data were collected and analyzed using the Rheology Advance software package. The curve modelling was achieved using the power law Ostwald-de-Waele relationship (1): n k γ τ ⋅ = (1) where τ is the shear stress (Pa), obtained by multiplication of the apparent viscosity and the shear rate; γ is the shear rate (s -1 ), "k", the consistency index (Pa•s n ), and "n" the flow behavior index (for pseudo plastic or shear-thinning fluid n < 1).
Temperature ramp tests were carried out between 25 • C and 60 • C at 5% strain and 5 Hz to analyze the effect of temperature. A total of 3 mL of hexadecan were poured onto the samples before each analysis to avoid water and acetic acid evaporations. Viscosity data were collected and analyzed using the Rheology Advance software package. The curve modelling was achieved using the power law Ostwald-de-Waele relationship (1): τ = k • γ n ( 1 ) where τ is the shear stress (Pa), obtained by multiplication of the apparent viscosity and the shear rate; γ is the shear rate (s -1 ), "k", the consistency index (Pa•s n ), and "n" the flow behavior index (for pseudo plastic or shear-thinning fluid n < 1).