dataesr/scientific-paragraphs-categorization huggingface dataset:
Note that OSIRIS does not measure in the northern polar region until late February due to a lack of sunlight at ∼ 06:00 and 18:00. NO 2 profiles at southern high latitudes have not been measured by balloon-borne instruments during the OSIRIS mission. Averaging kernels are not taken into account since the vertical resolution is similar between the NO 2 profiles from most of the selected validation instruments and from the three OSIRIS algorithms, namely the operational v3. 0, "fast", and the algorithm described herein. Results from the current algorithm will be treated separately for each of the forward model modes (1-D, 2-D, and 3-D) described in Sect. 2. 2. In Sect. 3, the 1-D profiles used in the validation are those processed by a network of computers (using a SZA cutoff of < 90 • ). The entire OSIRIS data record has now been processed using the 1-D algorithm and is currently available (University of Saskatchewan, 2017).
g. Sioris et al. , 2007). Thus, in Fig. 5 , we examine the standard error of the coincident profiles for OSIRIS and balloon data to compare the variability of each dataset, similar to  Kerzenmacher et al. (2008). The upper altitude limit of the data obtained from balloons launched by CNES (Centre National d'Études Spatiales) is 31 ± 2 km (Table  2 ). This excludes MkIV and SAOZ-BrO. From 31 down to 28 km, the balloon-borne NO 2 profiles show more scatter than any of the OSIRIS data products. This is likely due to the need to assume the NO 2 vertical distribution above float altitude for the remote sensors, which is particularly problematic in the tropics where the NO 2 profile typically peaks at a higher altitude than for the extratropics. A second factor is the smaller ab- sorption signal for the remotely sensing balloon instruments due to the short path lengths when observing altitudes near float.
Below 16 km, the balloon data clearly exhibit less scatter than OSIRIS, thereby quantitatively supporting the choice of balloon validation data for reasons discussed in Sect. 1. Kerzenmacher et al. (2008)  show that this is not true for NO 2 at ∼ 15 km measured by the ACE (Atmospheric Chemistry Experiment) satellite instruments relative to OSIRIS v3. 0 NO 2. Between the three OSIRIS products, "fast" exhibits the largest scatter at all altitudes, whereas the 2-D algorithm described here offers noticeably less scatter between 15 and 20 km as compared to the v3. 0 product. The 3-D algorithm takes 1. 5 h to retrieve a profile on the computer specified above and thus the entire set of balloon-coincident OSIRIS limb scans was not processed. The 2-D algorithm takes half of the processing time of the 3-D algorithm.
0 products, there are no altitudes in the lower stratosphere (below 24 km) with statistically significant average and median biases for the 1-D and 2-D products. This conclusion is not sensitive to the use of the MS approximation used for the 1-D product (see Sect. 2. 3) (not shown). While Figs. 6 and 7 address the systematic errors of the various OSIRIS products, it is also important to consider the precision of these data since a product whose biases in individual profiles average to zero could still fail to adequately capture the variability. This is potentially a greater concern for the v3. 0 product since it relies slightly on a priori NO 2 and vertically smooths the retrieved NO 2 when measurement precision is lacking. However,  Haley and Brohede (2007)  and  Haley et al. (2004)  show that these are very minor concerns as the measurement response and vertical resolution do not deteriorate significantly down to an altitude of 12 km.
The use of a fully spherical forward model is an important advantage, particularly at lower altitudes since, while the pseudospherical RTM errors are largest at the top of the retrieval range, the largest NO 2 retrieval errors due to the use of a pseudo-spherical RTM occur at low altitudes because a high tangent height reference is used in the retrieval. A model capable of modelling diurnal gradients in NO 2 also helps to improve the precision of the retrieved number density profile, particularly at the lowest altitudes where the horizontal gradients in NO 2 are sharpest and where the radiance is predominantly from the near side of the limb. of Toronto) provided the idea to use correlation as a statistic for validation. SALOMON-N2, SPIRALE, SAOZ, mini-SAOZ, and LPMA data were obtained from CNES/CNRS-INSU Ether website.
Acknowledgements. This work was supported by  Environment and Climate Change Canada  through a contribution to the  University of Saskatchewan. The  OSIRIS  project is supported by the  Canadian Space Agency. Daniel Zawada  ( University of Saskatchewan ) is acknowledged for helpful discussions regarding the high spatial resolution version of the SaskTran model. Alexei Rozanov  ( University of Bremen ) is acknowledged for sharing his experience with the weighting-function DOAS method. Patrick Sheese  (University www. atmos-meas-tech. net/10/1155/2017/Atmos. Meas. Tech. , 10,  1155-1168 , 2017.
, 2013). Biotinylation of subcellular structures, such as the inclusion membrane, can be monitored by microscopy. Further, purification of proximal or interacting proteins relies on the affinity and avidity of streptavidin for biotin. For this study, we have created Inc-APEX2 constructs and used them to examine the impact of overexpression of an early Inc (IncF) on inclusion development. We also present data demonstrating our ability to solubilize the chlamydial inclusion membrane and perform a subsequent pulldown. Importantly, completion of these studies will help us to determine specific roles for Inc proteins in the biogenesis and maintenance of the chlamydial inclusion membrane.
Seven to ten fields of view were taken from duplicate coverslips in two independent experiments. The fluorescent intensity (integrated density) and area of the inclusion were determined with ImageJ v1. 48 (National Institutes of Health, Bethesda, MD). Mean and standard error of the mean were calculated and graphed using GraphPad Prism 7. 0a software. An ordinary oneway ANOVA with Tukey's multiple comparisons post-hoc test was performed to test for statistical significance.
PVDF membranes were imaged using Odyssey CLx and processed using Image Studio version 5. 2 (LiCor Biosciences). After Western blotting, some PVDF membranes were also Coomassie stained using the following protocol. Membranes were rinsed with 100% methanol followed by one wash in Tris-buffered saline with 0. 1% tween 20 (TBS-T) for 5 min at RT. Membranes were stained with Coomassie Brilliant Blue R-250 (BioRad) for 2. 5 min at RT and then destained with two consecutive washes of 50:43:7, methanol:dH 2 O:acetic acid and 90:10 methanol: acetic acid, respectively. Air-dried membranes were imaged using GeneSnap software (SynGene).
Densitometry and Image Production All Western blots were analyzed using Image Studio Version 5. 2 software (LiCor Biosciences). Graphed data (averages and standard deviation or standard error of the mean) were produced using GraphPad Prism 7 software (GraphPad Software, La Jolla, CA). All figures were constructed using Adobe Photoshop elements 14 and Adobe Photoshop CS5 (Adobe Systems Incorporated, San Jose, CA). Any modifications to images were limited to adjustment of color balance in fluorescent images, or brightness and contrast in Western blot images. The inclusion sizes were measured using NIS elements basic research Version 3. 22 (Nikon).
2 nM aTc without biotin-phenol (A, bottom row), and wild-type Ctr L2 treated with both aTc and biotin-phenol (B), and mock infected HeLa (C). All images were taken with an Olympus Fluoview 1000 Laser Scanning Confocal Microscope (60x magnification with 2x zoom). Scale bars equal 10 µm. These images were obtained from coverslips that were removed from the 6-well plates used to produce the data in Figure  6. FIGURE 6 | Lysis conditions compatible with solubilization of inclusion membrane proteins and pulldown of biotinylated proteins. HeLa cells seeded in 6-well plates were infected with Ctr L2 transformant IncF-APEX2, wild-type Ctr L2, or mock infected with the aTc induction/treatment conditions, followed by the biotin-phenol additions as indicated. The cells remaining in the 6-well plates were lysed as described in the Materials and Methods, and cleared lysates (lysates) and the insoluble pellets (pellets) were resolved by SDS-PAGE, transferred to a PVDF membrane, and Western blotted for a transmembrane Golgi protein GM130 (A), chlamydial heat shock protein 60 (cHsp60) (B), inclusion membrane protein IncA (C), eukaryotic cytoskeletal protein tubulin (D), and biotinylated proteins with streptavidin (E).
ACKNOWLEDGMENTS We would like to thank  Emilie Gauliard ,  Kyle Kennedy , and  Ethan Thompson  for their technical assistance. We would also like to thank  Drs. Ted Hackstadt  ( NIAID, RML, Hamilton, MT ) for antibodies and  Rick Morrison  ( University of Arkansas Medical Center, Little Rock, AR ) for the chlamydial HSP60 antibody. We are appreciative to  Dr. P. Scott Hefty  ( Kansas University ) for sharing his inducible expression chlamydial plasmid, pASK_GFP_mKate2_L2. This work was supported by  NIAID   R15AI107727-01A1  and  R01AI114670-01A1  to ER, and  USD SSOM  start-up funds to SO.
Benchmark instances Three different sets of benchmark instances have been used: • Set 1 (S1): The IRP instances proposed by  Archetti et al. (2014). This set consists of 40 benchmark instances with |C| ∈ {5, 10, 15, 20} and a 3-period time horizon, i. e. |T | = 3. Note that larger instances were considered in  Archetti et al. (2014)  but we do not consider them in our experiments as they turned out to be too hard to solve for the FPVRP. • Set 2 (S2): The PVRP instances proposed by  Francis et al. (2006). This set consists of 24 instances with |C| ∈ {7, 9, 11, 15, 49} and time horizon |T | = 5. Instances were generated in a similar way to those used by  Francis et al. (2006)  and according to the database provided by one of the authors. Schedules for each customer are assigned according to their frequency of visits as explained in the following.
Acknowledgements The research of the last two authors has been partially supported by the  Spanish Ministry of Economy and Competitiveness end EDRF  funds through grant  MTM2015-63779-R (MINECO/FEDER ). The research of the third author has been partially supported by the  Mexican National Council for Science and Technology (CONACyT). This support is gratefully acknowledged. The authors are grateful to  Karen Smilowitz  for providing the necessary information to reproduce the set of instances S2 used in this paper. Thanks are due to both referees for their constructive comments, which have led to a considerable improvement of the manuscript.
The calculated or synthetic spectra are determined using Lifbase software  [10]. A small amount of H 2 was added in order to improve the sensitivity of the temperature measurements in the case of dry air. In other words, introducing a small percentage of H 2 in the plasma is an efficient way to better observe the OH (A-X) spectrum. We have ensured that this small amount of H 2 does not induce any effect on the thermal characteristics of the air plasma by observing the very good superposition of the NO γ spectra of the air plasma column with and without this small amount of H 2 (data not shown). The rotational temperature of the OH radical is assumed close to the gas temperature since the characteristic time of rotation-translation is very short. The relative uncertainty is estimated by varying the temperature of the simulated spectrum as long as the peak correlation remains upper than 0.
Temperature Effects The effective branching ratio ( ) 2 N a can be calculated from the room temperature quenching coefficients and the measured gas temperature determined by fitting  ). the experimental spectra recorded in the range from 306 nm to 310 nm with synthetic spectra calculated using LifBase software  [10]. Spectra were recorded along the axis of the air plasma column (Figure  10 ) and in the radial direction for different axial positions. It is important to underline that the gas temperature in the case of humid air (50% of humidity) is higher than the case of dry air. For instance, at 600 mbar, the gas temperature on the axis at the output of the nozzle (i. e.
Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.
Patient samples Bone marrow smears were collected from healthy donors (controls, n = 4) and AML patients (n = 6) at initial diagnosis to analyze number of nucleoli per cell and nucleoli morphology by immunofluorescence. In addition, RNA samples of five series (controls, series 1, series 2, series 3 and TCGA series) issued from bone marrow or blood samples were used to investigate clinical value of ribosome biogenesis factors (see characteristics in Table  1 ). Smears, controls, series 1, series 2 and series 3 were collected at Hopital Lyon-Sud (HCL, Lyon, France). AML samples corresponded to patients with de novo AML from initial diagnosis with a minimum of 15% of blast cell count. Control samples were issued from healthy donors selected as potential allograft donors. Series 3 was constituted of AML samples from series 1 and 2 for which clinical data were available (follow-up of survival patients up to 5 years).
The TCGA series was extracted from a public database hosting datasets issued from the Cancer Genome Atlas project (TCGA Research Network, Acute Myeloid Leukemia dataset). All samples were obtained at time of diagnosis with written informed consent at corresponding hospitals with approval of local ethics committees (Comited'Ethique de Lyon) that approved this study. Characterization of the classical cytogenetic markers was determined by the corresponding hospitals. Clinical annotations were available for the series 3 and TCGA (S1 Dataset).
Immunofluorescence and quantification Air dried bone marrow smears were hydrated with 1X PBS, fixed with 4% formaldehyde and permeabilized with 0. 5% Triton X-100. Immunostaining was performed using a rabbit anti-FBL antibody at 1/500 dilution (ab5821, Abcam), a mouse anti-NCL antibody at 1/2000 ([4E2] ab 13541, Abcam) and AlexaFluor 488 1 /AlexaFluor 555 1 conjugated secondary antibody (Molecular Probes). Following immunostaining, nuclei were stained with Hoechst 33342 (Molecular Probes), and smears were mounted with Fluoromount G mounting medium (Electron Microscopy Sciences). Images were collected with a x63 NA 1. 4 Plan-Apochromat objective on a Carl Zeiss LSM 780 confocal microscope. Image analysis and quantification were performed on wide-field images collected with a x40 NA 1. 30 Plan Fluor objective on a Nikon NiE microscope equipped with an Orca Flash 4 camera (Hamamatsu), and using the NIS Elements software (Nikon).
Analysis of TCGA AML dataset The Cancer Genome Atlas (TCGA) was queried (last query in July 2014) (The Cancer Genome Atlas-Data Portal. Available at https://tcga-data. nci. nih. gov/tcga/tcgaHome2. jsp). Clinical and pathological information from only 113 patients with AML were downloaded. Indeed, some AML cases lack information about patients' survival and AML cases with history of neoadjuvant treatment were excluded from the analysis since chemotherapeutic drugs have been shown to inhibit ribosome biogenesis that may thus affect expression of factors involved in ribosome biogenesis  [26]. Level 3 RNAseqv2 data were downloaded, corresponding to gene read counts that were generated from the IlluminaHiSeq platform and normalized using MapSplice to do the alignment and RSEM to perform the quantification  [27, 28].
Statistical analyses Statistical analyses were performed using GraphPad Prism 5. 0a (GraphPad Software, Inc). Median comparison between two unpaired groups was performed using the non-parametric Mann-Whitney test. Correlations between different methods or primers sets were tested using the non-parametric Spearman r test. Overall survival was measured from the date of diagnosis to death or censored at the last follow-up. Prognostic value of the different genes was estimated using the Kaplan-Meier method and the Log-Rank Mantel-Cox model was used to assess statistical significance. A cut-off based on data dispersion was used instead of an absolute cut-off since quantification of mRNA levels was measured using two different methods (RT-qPCR and RNA-seq). In particular, the 75 th percentile was used as a cut-off for all the datasets to defined "low" versus "high" expression since we observed that NCL is over-expressed in AML patients and that NCL median levels in AML patients correspond to the highest NCL levels in healthy donors.
NCL and NOP56, two factors involved in ribosome biogenesis, are overexpressed in AML patients Since nucleoli number and size were increased in AML blasts, we investigated whether some factors of ribosome biogenesis were over-expressed in AML samples. We collected a control series of healthy donors and two AML series from initial diagnosis (series 1 and 2) (Table  1 ). Gene expression was quantified by high throughput qPCR using microfluidic technology (Fluidigm system devices). This technology allows to analyze expression of 48 genes in 48 samples in a single run and thus to reduce the amount of samples required. In our hand, a strong statistical correlation was observed between data generated by high throughput qPCR and classical qPCR quantification (S4A Fig) as already shown by others  [31, 32].
To validate the use of NCL and NOP56 expression in predicting AML outcome, an additional, independent series was studied (series TCGA, see Table  1 ). We extracted expression profiles of the seven genes of interest (C-Myc, NPM1, NCL, FBL, NHP2L1, NOP56 and NOP58) determined by RNA-seq of AML samples from the TCGA dataset (TCGA Research Network, Acute Myeloid Leukemia dataset). Filters were used to restrict the analysis to primary AML samples thus allowing the collection of 113 samples to build the validation series. Dichotomization of expression levels was performed using the 75 th percentile as a cut-off to conserve similar strategy within the study (S6B Fig). Using the TCGA dataset, no significant association was observed between NOP56 expression levels and AML patient's outcome (Table D in S1 File).
0164). NCL expression levels could therefore be used as a prognostic factor for survival in elderly AML patients. In addition to age, cytogenetic alterations is an important risk factor  [1, 2, 6, 14]. However, the main issue with the cytogenetic risk classification resides in the stratification of AML patients belonging to the intermediate and poor risk groups since these two groups have almost similar outcomes  [4, 5, 25]. This finding was confirmed in the TCGA dataset (S7A Fig). We thus investigated the use of NCL expression in improving cytogenetic risk classification in AML patients of the TCGA series using Kaplan-Meier and Cox regression analyses. While NCL expression had no significant impact on patient outcome in the favorable and poor risk groups, enhanced NCL expression was associated with shorter overall survival in the intermediate group (S7B Fig and  Table  A in S1 File).
Overall, our data suggest that NCL expression could help in identifying prognostic subgroups within the current cytogenetic risk classification. Finally, we investigated whether NCL is an independent marker of prognosis in AML patients using the TCGA series. We performed a multivariate analysis to adjust possible confounding variables (age at diagnosis, cytogenetic alteration and NCL mRNA levels) on all AML samples issued from the TCGA dataset (n = 113). The best model associated with poor overall survival contained three independent markers: age at diagnosis (P = 0. 00012 ÃÃÃ ); cytogenetic alterations (P = 0. 0170 Ã ); and NCL mRNA levels (P = 0. 0230 Ã ). These analyses demonstrated that NCL expression is associated with poor overall survival independently of these other common prognostic factors.
Analysis of NTSR expression at the protein level confirmed the mRNA results: NTSR2 was overexpressed in B-CLL, whereas NTSR1 was undetectable (Figures  1c  and d ). The abnormal expression of NTSR2, independent of B-CLL stage and progression, led us to investigate the roles of the primary mechanisms responsible for GPCR overexpression, that is, gene mutations and chromosomal abnormalities. 9 To this end, we sequenced NTSR2 and analyzed the karyotypes of 10 B-CLL patients. None of the B-CLL cases harbored mutations in the NTSR2 gene, except for two patients with a silent polymorphism (rs114415067, pH55H) (data not shown). Moreover, NTSR2 mutations are present in only 0. 3% of the 19 141 samples in COSMIC v62, indicating that NTSR2 mutations are rare in all combined pathologies. 15 ogether, the significant increase in NTSR2 mRNA and protein levels suggested that NTSR2 plays a role in the pathogenesis of B-CLL, regardless of the biological and clinical features of this disease.
After washing (tris-buffered saline/0. 1% Tween-20), the immunoreactions were detected by incubation for 2 h at RT with horseradish peroxidase-conjugated secondary Ab against mouse or rabbit Ig (P0447 and P0448, respectively, Agilent Technologies, Santa Clara, CA, USA), revealed with the Immobilon Western Chemiluminescent HRP Substrate (Merck Millipore). Western blot were detected using Bioimaging Systems (GeneSnap and GeneTool; Syngene, Cambridge, UK). Densitometric analyses were performed using the ImageJ software (NIH, Bethesda, MD, USA).
The experimental diet (unbalanced, high fat), had a 3200 kcal/kg energy content. Nine pigs were fed this diet, which had a 5x higher fat level (obtained by adding tallow), 13% higher protein level and a 4% addition of saccharose compared to the standard diet. Pigs in this group had unlimited access to food and consumed 4kg/pig/day during the period of highest food intake. The third (the high fat/low fat) group, consisting of eight pigs, was fed an unbalanced diet for nine months and then a standard, balanced diet for three months. All diet ingredients are included in supplementary data information (S1 Text). Blood was drawn twice-at the beginning and at the end of the study. The complete blood count (CBC) was analyzed using an ABC-Vet analyzer, while the biochemical analyses were performed using the MaxMat Pl analyser.
The clinical data is summarized in Table  1. In addition we have checked glucose and insulin levels and we have not found any significant differences between the groups. The animals were sacrificed at the end of the study and tissue sample including subcutaneous fat and aorta were obtained for further analysis. Basic histopathological analysis included haematoxylin and eosin staining of the arterial rings from the same site on the femoral artery of all the animals and measurements of intima, media and adventitia thickness. Thickness of intima was chosen as the histological marker of atherosclerosis and compared with ultrasonographic measurements of the intima-media complex. Clinical evaluation of animals was performed every 3 months. Clinical measurements included zoometric data, arterial blood pressure and heart rate, ultrasonographic evaluation of arteries for measurements of intima-media thickness (Table  2 ).