dataesr/scientific-paragraphs-categorization huggingface dataset:
Oncogene-associated exon expression profile in AML cells WT1 and DEK are frequently overexpressed in AML and can interfere with spliceosome activity  [7] [8] [9] [10] [11] 14]. We hypothesized that the expression of these two oncogenes might influence exon expression patterns in AML cells. We thus used Affymetrix HTA2 exon arrays to examine the exon expression profiles of three AML cell lines (MOLM13, Kasumi-1 and KG1) that had normal or knocked-down levels of WT1 or DEK gene expression. shRNA-WT1 significantly reduced the level of WT1 mRNA and protein expression in the three cell lines (Figure  S1A ) and similar results were obtained with DEK (data not shown). Microarray data were crosscompared between the cell lines and only statistically significant modifications (p < 0. 05) were selected.
We next investigated whether the mRNA of genes that are frequently mutated in AML are misspliced in these cell lines and patient-derived samples. We randomly selected 40 genes that are frequently mutated in AML (Supplementary Table  10 )  [27, 28]  and found that 13 of these genes (32. 5%) were mis-spliced in at least one leukemic condition. As a control, we randomly selected from the NCBI database (http://www. ncbi. nlm. nih. gov/ge ne/?term=acute+myeloid+leukemia) 40 mRNAs that are expressed in AML cells. Five of these genes (12. 5%) were mis-spliced in at least one leukemic condition (p = 0. 03, Pearson's Chi-squared test).
Affymetrix exon array hybridization and array data One μg of total RNA was labeled and purified with TRIzol with Affymetrix reagents according to the manufacturer's instructions. Hybridization cocktails containing 5-5. 5 μg cDNA were prepared and hybridized to Affymetrix-GeneChip Human Exon HTA2 arrays (Affymetrix). Affymetrix Expression Console Software was used for quality assessments. Affymetrix exon array data treatment was performed using FasterDB annotation (https://fasterdb. lyon. unicancer. fr/) and the data were normalized using quintile normalization. The background correction and probe selection were performed as previously described  [49].
Exon-specific polymerase chain reaction (ESPCR) Splicing events were annotated on the FASTERDB database and primers were designed to encompass alternative splicing events using Primer 3. PCR reactions were performed using the Herculase II Fusion DNA Polymerase (Agilent Technologies) in 30-35 cycles and the resulting products were analyzed by agarose gel electrophoresis. Primer sequences are available on request. Samples were analyzed in duplicate.
ACKNOWLEDGMENTS AND FUNDING This work was supported by the  Agence Nationale pour la Recherche (ANR) ,  Association Laurette Fugain ,  Association pour la Recherche sur le Cancer (ARC) ,  Fondation de France ,  Hospices Civils de Lyon, University Lyon-1 ,  Centre National pour la Recherche Scientifique (CNRS) ,  Institut National de la Santé et de la Recherche Médicale (Inserm) ,  Association Guillaume Espoir, Amgen ,  Celgene ,  Pierre Fabre  and  Novartis. A. M. M. was supported by bursaries from the  Islamic Development Bank  and from the  Fondation pour la Recherche Médicale , F. M. is supported by  Inserm  and by  Hospices Civils de Lyon  ( AVIESAN CHRT 2010 ). E. W. is supported by  Hospices Civils de Lyon and Lyon I University.
At 131 min, the gradient returned to 5% to re-equilibrate the column for 30 min before the next injection. Two blanks, one short 40 min step gradient and one 60 min linear gradient, were run between triplicates to prevent sample carryover. Peptides eluting from the column were analyzed by data dependent MS/MS, using top-10 acquisition method. Briefly, the instrument settings were as follows: resolution was set to 70,000 for MS scans and 17,500 for the data dependent MS/MS scans in order to increase speed. The MS AGC target was set to 3. 10 6 counts, whereas MS/MS AGC target was set to 5. 10 4. The MS scan range was from 400 to 2000 m/z. MS and MS/MS scans were recorded in profile mode. Dynamic exclusion was set to 20 s duration. Each sample was analyzed in biological triplicate by nanoLC/MS/MS.
Each biological replicate was acquired in three technical replicates. Data Processing Following LC-MS/MS Acquisition-The MS files were processed with the MaxQuant software version 1. 4. 1. 2 and searched with Andromeda search engine against the NCBI F. tularensis subsp. novicida database (release 28 -04-2014; 1719 entries). To search parent mass and fragment ions, we set an initial mass deviation of 4. 5 ppm and 0. 5 Da, respectively. The minimum peptide length was set to seven amino acids and strict specificity for trypsin cleavage was required, allowing up to two missed cleavage sites. Carbamidomethylation (Cys) was set as fixed modification, whereas oxidation (Met) and N-term acetylation were set as variable modifications. The false discovery rates (FDRs) at the protein and peptide level were set to 1%.
Scores were calculated in MaxQuant as described previously (Cox and Mann). The reverse and common contaminants hits were removed from MaxQuant output. Proteins were quantified according to the MaxQuant label-free algorithm using LFQ intensities  (23, 24) ; protein quantification was obtained using at least two peptides per protein. Statistical and bioinformatic analysis, including heatmaps, profile plots, and clustering, were performed with Perseus software (version 1. 4. 1. 3) freely available at www. perseus-framework. org. For statistical comparison, we set two groups, each containing biological and technical triplicates, and we then filtered the data to keep only proteins with at least nine valid values out of 18. Next, the data were imputed to fill missing data points by creating a Gaussian distribution of random numbers with a standard deviation of 33% relative to the standard deviation of the measured values and 1.
8 standard deviation downshift of the mean to simulate the distribution of low signal values. We performed a t test, with a permutation based testing correction that was controlled by using a false discovery rate threshold of 0. 05, 250 randomizations. Hierarchical clustering of proteins that survived the test was performed in Perseus on logarithmized LFQ intensities after z-score normalization of the data, using Euclidean distances using default parameters and setting 12 clusters for the row tree. All MS data have been deposited in the ProteomeXchange database with identifier PXD001584 (http://proteomecentral. proteomex change. org/dataset/PXD001584). Annotated spectra can be consulted using MS-viewer  (25)  with the key a9omruthfd.
These belonged to six clusters (241, 244, 296, 150, 90, 122), also regrouping a wide variety of predicted functions and more than 40 hypothetical proteins of unknown function. Altogether, the 842 proteins belonged to multiple pathways, according to the KEGG pathway database for F. novicida (available at http://www. genome. jp/kegg-bin/show_organism? menu_typeϭpathway_maps&orgϭftn). Of note, all the ribosomal proteins, as well as all the proteins involved in branched-chain amino acid (BCAA) biosynthesis, were present only in lower or unchanged amounts in the ⌬argP mutant (supplemental Fig. S3 ). ArgP is Involved in Phagosomal Escape-We followed the subcellular localization of the ⌬argP mutant in infected cells by confocal microscopy. Intracellular localization of bacteria or LAMP-1 (used as a specific marker of phagosomes) was analyzed using specific antibodies and their colocalization was monitored at three time-points (1 h, 4 h, and 10 h postinfection; Fig.
4A ). Quantification of each colocalization was performed with the Image J software (Fig. 4B ). In cells infected with wild-type F. novicida, colocalization of bacteria with LAMP-1 was only 8% at 1 h and remained in the same range throughout the infection, showing that most bacteria escape the phagosome rapidly. In contrast, the ⌬FPI mutant strain showed high colocalization with LAMP-1 throughout the infection (87% at 1 h, 90% at 4 h, and 91% at 10 h). In this assay, the ⌬argP strain showed a severe delayed phagosomal escape. Indeed, at 4 h, 85% LAMP-1 colocalization was still observed. Partial phagosomal escape was detected only at 10 h of infection (with less than 55% bacteria still associated with LAMP-1). Taken together, these results demonstrate that argP gene is necessary for the bacteria to reach cytosol.
g. phosphatases (  53 )) as well as metabolic or stress resistance functions (e. g. biotin biogenesis, oxidative stress  (13, 54) ) have been shown to contribute, directly or indirectly, to escape. This study reveals that ArgP-dependent arginine acquisition constitutes a novel player in phagosomal egress. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteome central. proteomexchange. org) via the PRIDE partner repository with the data set identifier PXD001584. We thank the PRIDE team (http://www. ebi. ac. uk/pride/) for deposition of the mass spectrometry proteomics data. In wild-type Francisella (WT, upper panel), import of arginine mediated by the transporter ArgP, promotes ribosomal protein synthesis (R), a pre-requisite for efficient protein (P) syntheses, a pre-requisite for membrane disruption and cytosolic escape.
Airborne platforms can be positioned at appropriate altitudes for dedicated remote sensing surveys such as above/below radiatively active layers of mineral dust. Measurements on aircraft platforms provide the ability to link together spatial and temporal features which are simply not accessible through fixed ground sites or satellites or even a combination of both. Furthermore, specifically in the June 2011 intensive observation period (IOP), two aircraft were operated and their combined capabilities meant that specific events could be followed through staggered missions. Finally, the combination of ground, airborne and satellite observations provide the fullest picture possible of the area of interest. During 2011 and 2012 an extensive data set was collected as part of the Fennec intensive observation programme.
Lidar The BAe146 aircraft operates a commercial Leosphere ALS450 backscatter lidar suitable for aerosol and thin cloud observation  (Marenco et al. , 2011). A description of the lidar system is provided by  Chazette et al. (2012)  and technical information is available in Table  1  of  Marenco et al. (2014). The nadir-viewing lidar provides elastic backscatter at 355 nm and features an uncalibrated depolarisation channel, used qualitatively to distinguish depolarising layers. Data are recorded at a vertical resolution of 1. 5 m and an integration time of 2 s, giving a horizontal resolution of approximately 200 m at aircraft speeds. The instrument is lightweight, has a relatively small receiver aperture of 15 cm diameter, has a 12 mJ pulse energy (20 Hz PRF) output and requires a low level of maintenance which makes it ideal for frequent operation aboard the BAe146 aircraft.
Airspeed is calibrated similarly. The radome transducers are calibrated at a calibration laboratory annually, or as determined by inspection of the data for drifts or other artefacts. The inertial navigation unit (INU) alignment is assessed annually with a physical survey for pitch, roll, and heading. AOA and angle of sideslip (AOSS) calibrations derive from AOA/AOSS flight manoeuvres that were carried out when the facility was commissioned, as they are physically dependent on the radome mounting. These were subsequently validated to confirm this. The AOA/AOSS are further corrected using yawing orbits, where further corrections are introduced to these quantities. True airspeed is corrected using reverse-heading manoeuvres, where the correction minimises the difference in derived upward/downward wind measurements.
Access to data UK-Fennec FAAM aircraft data from the BAe146 is available at the British Atmospheric Data Centre (BADC, http: //badc. nerc. ac. uk/home/index. html) and is freely available subject to registration. Fennec-France aircraft data are available from the Sedoo (Service de données de l'OMP, http: //catalogue. amma-international. org/) and is attached to the AMMA database, subject to free registration, listed under "Fennec" in the project list.
18 • N. Lidar observations of this cell 13 min prior to the intersection provided a cloud top height of 6. 65 km, which is estimated to be at -15. 0 ± 0. 2 • C. The lidar data showed no links to, or particle flow between, any other clouds. Particle images recorded by the CIP showed that this cloud consisted of pristine hexagonal plates. Freezing at this warm temperature is uncommon even for clouds in the vicinity of a source of IN  (Kanitz et al. , 2011; Ansmann et al. , 2008; Sassen et al. , 2003; Raymond and Blyth, 1989 ). An explanation could be the very high dust concentrations acting as IN in the heart of the Sahara. The descent to 500 m provided a measurement of the aerosol input into the cloud. At the surface particle concentrations above 0. 13 µm diameter measured by the PCASP and CDP ranged between 60 and 80 cm -3 south of 25.
75 µm 2 cm -3 (count median diameters of 0. 38 to 0. 49), the ozone mass mixing ratio decreases to 41-44 ppb. The spread in ozone concentrations at mean surface areas of 0. 45 µm 2 cm -3 is associated with crossing into a harmattan airflow. These in situ observations suggest that increased mineral dust surface area associated with fresh dust uplift and a large coarse-mode contribution to the size distribution act as a route for the reduced ozone concentrations. However, from the analysis presented here, it is not possible to unequivocally conclude if the air mass initially contained lower ozone concentrations and that the mineral dust was subsequently uplifted, or if mineral dust uplift could have contributed to the reduced ozone concentrations observed. There is scope within the Fennec data set to further investigate air mass source regions, potentially with Lagrangian study methods.
Looking at the middle panel, the longitudinal behaviour of the AOD derived from all three instruments is generally in good agreement although SEVIRI tends to show consistently higher AODs than those derived from the lidar and from MODIS. The MODIS retrievals contain more data gaps as a result of various data quality tests: both the lidar and SE-VIRI retrievals and the RGB composites suggest that these tests may be slightly too severe as there is no clear evidence of a break in the aerosol layer or the presence of cloud. The intense pink colour of the composite at the western edge of the track would suggest the largest dust loadings are located here, associated with a thick dust plume at an altitude of ∼ 3 km and another distinct layer observable at ∼ 5. 5 km seen in the lidar profile (which may have originated from Mali on 19 June).
By the eastern end of the track, the AODs measured by MODIS, SEVIRI and the lidar are slightly smaller than the values seen at the western end, the dust is much more uniformly spread throughout the lowest ca. 5 km of the atmosphere, and the intensity of the RGB signal is somewhat reduced. Further work has explored co-located aircraft and satellite data in more detail, utilising a more extensive suite of satellite instruments (such as the Multi-angle Imaging Spec-troRadiometer (MISR) instrument on Terra and the IASI instrument on the METOP satellites  (Banks et al. , 2013) , and between the BAe146 in situ measurements and spaceborne lidar CALIOP  (Pappas et al. , 2015). In the former study, the differences between retrievals were investigated, including an evaluation of the sensitivity of the retrievals to variations in dust loading, to atmospheric conditions (such as column water vapour), to surface features (such as albedo) and to aerosol height.
As diagnosed by  Banks et al. (2013) , when the dust loadings are high, the SEVIRI retrievals appear most capable of retrieving the appropriate AODs, whereas the other retrievals are biased low. On the other hand, the SEVIRI retrievals are most sensitive to meteorological conditions, especially column moisture, under high levels of which the SEVIRI-retrieved AODs are biased high; conversely, the MODIS Deep Blue and MISR aerosol retrievals appear to be relatively insensitive to such factors. The aircraft data will be of substantial benefit to interpreting the "desert-dust" RGB imagery.
2 µm and greater than 14 µm  (Dubovik et al. , 2002). Unfortunately the flights during Fennec when large particles were strongly evident did not take place close to AERONET sites, due to the remoteness of the flight locations. Ryder et al. (2013b)  find that particle sizes are larger close to dust sources in remote locations, and  Ryder et al. (2013a)  show that giant particles (d > 37. 5 µm) are a feature of freshly uplifted dust events, and some longrange transported cases. This should be a caution for using AERONET retrievals as a basis for dust size distributions over the central Sahara, particularly since they only extend to 30 µm diameter and the tails of the size distributions are constrained to very small values  (Hashimoto et al. , 2012). Further studies will examine aircraft and sun-photometer data from both 25 June 2011 and 18 June 2012, in terms of in situ aircraft measurements, airborne and ground-based radiation measurements, and using both the AERONET and SKYRAD retrievals for the inversion of sun-photometer radiances.
The aircraft flew the track twice, once in the morning (b607) and once in the afternoon (b608), allowing the evolution of the atmosphere over time to be studied. Dropsonde measurements were obtained during the outward and return flight at fixed locations. Dropsonde data were interpolated to reference times at each location thereby creating a snapshot of the state of the atmosphere in the study region at the reference times. Engelstaedter et al. (2015)  analysed the observed SHL characteristics and evaluated the performance of the UK Met Office limited area model for Africa (Africa-LAM). They identified two moisture transport pathways, one curving around the SHL core in the north (especially pronounced in a morning near-surface layer), and the other going towards the northeast within the roughly 2 km deep monsoon surge.
-Vertical profiles of turbulent fluxes have revealed unusual characteristics of entrainment and detrainment of thermals in the deep, dry SABL, which are a challenge for BL schemes in global models. -Unique in situ observations suggest that precipitation is recycled as it is evaporated into BL air that feeds clouds (a common feature of the SABL), increasing the total water content of subsequent clouds and increasing the moisture content at mid-levels in the SABL. Observations suggest cloud-processing of dust and subsequent evaporation alters the size distribution of dust. -In one case, a comparison of aircraft lidar data with satellite-based measurements from SEVIRI and MODIS shows good agreement as to the spatial distribution of dust but they disagree as to the loading, which may be indicative of different sensitivities to varying meteorological conditions.
These will be further exploited through the Fennec Earth observation and modelling programmes. The Supplement related to this article is available online at doi:10. 5194/acp-15-8479-2015-supplement. MODIS data used in this paper were produced with the LAADS online data system, developed and maintained by NASA Goddard, and we also acknowledge the MODIS scientists and associated NASA personnel for the production of the data used in this research effort. Flight forecasting would not have been possible without the model products made available especially for the Fennec project particularly the UK Met Office, the Météo-France AROME model team and the DREAM model team. Edited by: R. Sullivan.
Acknowledgements. Core project funding for Fennec was from the UK Natural Environmental Research Council (NERC) under grant NE/G017166/1. In addition, Fennec received support from the NERC National Centre for Atmospheric Science (NCAS), the Agence Nationale de la Recherche (ANR no. 2010 BLAN 606 01), the Institut National des Sciences de l'Univers (INSU/CNRS) through the LEFE programme, the Centre National d'Etudes Spatiales (CNES) through the TOSCA programme and Météo-France. Airborne data from the BAe146 were obtained using the BAe-146-301 Atmospheric Research Aircraft operated by Directflight Ltd and managed by FAAM, which is a joint entity of the NERC and the UK Met Office. Airborne data from the F20 were obtained using the Falcon 20 Environment Research Aircraft operated and managed by SAFIRE, which is a joint entity of CNRS, Météo-France & CNES.
Existing "top down" measures of trade costs have been computed for major economies for which data on production and trade are readily available, but ours, building on the ESCAP Trade Cost Database developed by some of the authors in 2011, is the first contribution to include a wide range of both developing and developed countries. Our database includes 178 countries, compared with a maximum of 27 covered by Jacks et al. (2011). 2   Our paper also adds to the literature by disaggregating trade into two macro-sectors, agriculture and manufacturing. Existing estimates largely use total trade only, without providing any sectoral details (e. g. ,  Jacks et al. , 2011 ). An exception is  Chen and Novy (2011) , who use industry-level data, but they only cover European countries and thus do not address the issue of trade costs in the developing world.
Box 2: Trade Costs and Country Dialogue-The Case of the Maghreb The proposed dataset scales up recent experiments to use trade costs data as a tool for policy making at the World Bank  (Arvis and Shepherd, Forthcoming)  and UN ESCAP  (Duval and De, 2011; Duval and Utoktham, 2011; and Duval and Utoktham, Forthcoming). For instance, two of the authors have been involved in a project designing a program in trade facilitation and regional infrastructure for the countries in the Maghreb in North Africa  (Algeria, Libya, Mauritania, Morocco, Tunisia). These countries trade very little between themselves (3-5 % of their trade).
Sensitivity of Trade Costs in Manufactured Goods to Listed Factors (2005) Note: Figure presents standardized regression coefficients (betas) from the models described in Table  9. Against this background, the paper proceeds as follows. The next section introduces our methodology for measuring trade costs, and situates it within the broader gravity model literature. Section 3 presents our dataset and discusses the main issues faced in compiling it. The first part of section 4 provides some initial results on trade costs in the developing world, focusing on differences across countries, sectors, and time periods. To better understand the determinants of trade costs, the second part of Section 4 conducts an econometric decomposition based on standard gravity data as well as relevant policy variables.
The World Bank has produced a number of such measures, including tariff (TTRI) and non-tariff barriers (OTRI)  (Kee et al. , 2009). Although useful indicators of trade policy settings, these TRIs suffer from the limitation that they are "bottom up" measures: they take account of those sources of trade costs included in the datasets used to build them, but not other potential sources. For instance, the OTRI relies heavily on TRAINS and other datasets of non-tariff measures, which are well known to provide only partial coverage at best. Furthermore, these indices leave out other major sources of trade costs, such as transport costs, and differences in cultural or legal heritage between countries which magnify the costs of doing business across borders. The only attempt to unify the literature on the various determinants of trade costs is  Anderson and Van Wincoop (2004).