dataesr/scientific-paragraphs-categorization huggingface dataset:
Line-ofsight values of individual observations are divided by the air-mass factor of the observation, the coefficient needed to obtain vertical amounts. This technique is the same as the one used to measure stratospheric constituents like ozone and NO 2 but extended for tropospheric constituents like water vapour. Note that multi-scattering effects are enhanced at twilight and cannot be easily evaluated, and therefore the AMF corrected accordingly. Because the SAOZ operates permanently and observations are possible even during bad weather conditions (rain, clouds, etc. ) data are available twice daily, morning (here and after a. m. values) and evening (p. m. ) averages, all year round, depending on technical problems. Note that H 2 O data presented here are preliminary real-time data, as they were not validated before in peer-reviewed publication.
Results and discussion For this study we analysed and compared two VCD data sets of H 2 O above OHP. The satellites data sets are issued from SCIAMACHY, GOME and GOME2. The groundbased instruments are Elodie and SAOZ. Table  2  presents the temporal coverage for these data sets for each instrument. We must indicate that data are available in various temporal and geographical samplings and for this study the comparison has been made in making monthly averages first, to maximise the number of coincidences that satisfy the temporal and spatial collocation criteria (as indicated for all instruments in Sect. 3) and then compare together the monthly means of each instrument.
Inter-comparison of ground-based measurements Monthly averages of the total column water vapour measured by SAOZ and Elodie, from 1995 to 2004 above OHP, both exhibit a clear annual variation (Fig. 2 ). SAOZ can measure H 2 O even in the presence of clouds, in contrast to Elodie which measures only by clear skies. SAOZ values are then expected to be slightly larger in comparison with Elodie because of the higher occurrence of cloudy days (i. e. days with more H 2 O in the atmosphere) in the SAOZ series. For this reason, we have only selected the daily measurements of SAOZ that also exist in the Elodie data set (clear night conditions). In taking into account the coincident daily measurements, we have eliminated most of the cloudy days in the SAOZ data set. The measurements of Elodie and SAOZ have trapped similar annual behaviours (Fig.
2 ), however, with small differences which appear sometimes during maximum or minimum values. The correlation coefficient is R = 0. 8, and indicates a high correlation between the two types of measurements. We can see also note that for the year 2003 in the SAOZ dataset, the maximum of the seasonal cycle of this year is low relative to other years, due to a change in the absorption cross section (convolution) and the spectrum of reference for this year (problem in the spectrometer slit). Figures.
Comparison between ground-based and satellite measurements at OHP In order to examine the representation of the satellite estimates of H 2 O above OHP compared to the ground-based measurements, we compared the two types of data sets. As we mentioned above, the three satellites of this study utilise the AMC-DOAS algorithm to retrieve the VCD. An air-mass correction factor in the algorithm effectively removes overly cloudy scenes, then the AMC-DOAS products are cloud-cleared  Mieruch et al. (2008). To make the comparison between the satellites and SAOZ measurements, we selected only the morning measurements of SAOZ that also existed in the satellites data sets, as it is the nearest period of their measurements. In -The measurements of GOME and SAOZ are in good agreement with a correlation of high-order (0.
Period of measurements Table  4  presents the time of measurements for each instrument in summer and in winter. According to this table we can see that there is a significant discrepancy between the time of measurements of ground-based instruments and the overpass times of the satellites above OHP, but also between the measurements of ground-based instruments themselves. The difference is negligible between satellites themselves. How can these gaps in time contribute to the difference between their measurements? To answer this question, we looked at the diurnal cycle of H 2 O VCD above OHP provided by OPERA. The OPERA data are derived from operational analysis from 2002 to 2011 by the ECMWF (European Center for Medium Range Weather Forecast). These measurements were obtained every 6 h from January 2002 to April 2011.
Process of bioinformatics study Our study was performed in two steps: (i) the nucleotide sequences of the autophagy genes-Atg5, Becn1, Atg7, Atg10, Atg12, Atg16l1, Gabarap, Gabarapl2, Map1lc3b, Nbr1, p62 (Sqstm1)-were imported from various mammalian species (EnsEMBL database, http://www. ensembl. org/) using the Ensembl Compara Perl API (http://www. ensembl. org/info/docs/api/compara/index. html). Sequences including up to 4000 nucleotides (nt) upstream from the transcription start site (TSS) were curated: all positions containing gaps and missing data were eliminated. Evolutionary analyses were conducted with MEGA5 software (http://www. megasoftware. net/). This step enabled us to check database annotations and eliminate sequences that were impossible to align with the other homologous mammalian genes; (ii) the full or partial consensus AARE (5 0 -TGATGMMAH-3 0 ) and CHOP-RE (5 0 -MRVHTGCAAYCYBY-3 0 ) Transcription Factor binding IUPAC sequences were searched in all retained mammalian promoter sequences (up to 4000 nt upstream from the TSS) using the 'Scan sequence with IUPAC-patterns' tool (Genomatix Software GmbH, Munich, Germany, http://www.
Scanning of the promoter sequences with IUPAC patterns (Genomatix Software GmbH, Munich, Germany) revealed that the 5 0 flanking region of these genes contains a putative AARE sequence (5 0 -TGATG MMAH-3 0 ) (Supplementary Figure  S3 ). ChiP assays performed with primer sets covering the AARE, anti-ATF4 and anti-CHOP antibodies confirmed that only ATF4 was bound to the promoter. In the second class, the induction of Nbr1 and Atg7 in response to leucine starvation was dependent on ATF4 and CHOP as described above for p62 (Figure  5B ). The promoter of these two genes also contains a putative AARE sequence (Supplementary Figure  S3 ). The ChIP assay clearly showed that both ATF4 and CHOP were bound to the AARE, and double ChIP confirmed that these two factors belonged to the same protein complex.
In CHOP-ATF4 double-ChIP assays, DNA fragments were first immunoprecipitated with CHOP antibody, eluted, and then subjected to the second immunoprecipitation with ATF4 antibody or normal rabbit IgG antibody. The enrichment of CHOP/ATF4 proteins was analyzed by qPCR using primer sets specific for Nbr1 and Atg7 promoters. In C/EBPb-CHOP double-ChIP assays, DNA fragments were first immunoprecipitated with C/EBPb antibody, eluted and then subjected to the second immunoprecipitation with CHOP antibody or normal rabbit IgG antibody. The enrichment of C/EBPb-CHOP proteins was analyzed by qPCR using primer sets specific for Atg10, Gabarap or Atg5 promoters. Data were plotted as the percentage of antibody binding versus the amount of PCR product obtained using a standardized aliquot of input chromatin (% of Input).
Data were plotted as the percentage of antibody binding versus the amount of PCR product obtained using a standardized aliquot of input chromatin (% of Input). In CHOP-ATF4 double-ChIP assays, DNA fragments were first immunoprecipitated with CHOP antibody, eluted, and then subjected to the second immunoprecipitation with ATF4 antibody or normal rabbit IgG antibody. The enrichment of CHOP/ATF4 proteins was analyzed by qPCR using primer sets specific for Nbr1 and Atg7 promoters. In C/EBPb-CHOP double-ChIP assays, DNA fragments were first immunoprecipitated with C/EBPb antibody, eluted and then subjected to the second immunoprecipitation with CHOP antibody or normal rabbit IgG antibody. The enrichment of C/EBPb-CHOP proteins was analyzed by qPCR using primer sets specific for Atg10, Gabarap or Atg5 promoters.
ACKNOWLEDGEMENTS We are grateful to  Drs D. Ron  and  H. Harding  ( Institute of Metabolic Science, Cambridge, UK ) for the gift of ATF4-and  CHOP-deficient MEFs  and CHOP expression plasmids. The authors thank  Drs D. Be´chet ,  A. Darfeuille-Michaud  and  J. C. Pointud  for helpful discussions. FUNDING  Institut National de la Recherche Agronomique (INRA) ;  Fondation ARC pour la Recherche sur le Cancer. Funding for open access charge:  INRA.
PDB codes 1o8a (ligand-free) and 2xy9 (FII-bound) used for C-ACE; 2c6f (ligand-free) and 2xyd (FII-bound) for N-ACE; 2x8y for ligand-free AnCE. Rmsd of all atoms for main chain/side chain ( A) share similar K i for C-ACE and thus the presence of FII-B at the allosteric site does not seem to influence the inhibition potency. It would also suggest that the presence of FII-B is only possible through interaction with FII-A. The catalytic channel is known to show flexibility in accommodating larger ligands. The crystal structure of C-ACE in complex with the bradykinin potentiating peptide (BPPb) demonstrated this capacity through movement of the helices capping the channel  [45]. Noticeably, FII-B occupies the same pocket as the N-terminus of the BPPb peptide. This secondary site might therefore be an attractive target for allosteric ligands that would prevent substrate binding.
Data reduction was carried out by using the CCP4 program SCALA  [54]. Initial phases for structure solution were obtained using the molecular replacement routines of the PHASER program  [55]. The atomic coordinates of C-ACE (PDB code 1O8A  [26] ), N-ACE (PDB code 2XYD  [43] ) and AnCE (PDB code 2X8Y, [42]) were used as a search model for their respective complexes. The resultant solutions were refined using REFMAC5  [56]  and adjustment of the models was carried out using COOT  [57]. Water molecules were added at positions where F o À F c electron density peaks exceeded 3r and potential hydrogen bonds could be made. Based on electron density interpretation, the inhibitor and sugar moieties were added in the complex structures and further refinement was carried out. The coordinates and parameter files for the dual inhibitor were generated using the PRODRG server  [58].
Validation was conducted with MOLPROBITY  [59]. Figures were drawn with PYMOL (DeLano Scientific, San Carlos, CA, USA). Hydrogen bonds were verified with the programs HBPLUS  [60]  and LIGPLOT  [61]. The detailed refinement statistics for the complex structure are given in Table  1. The atomic coordinates and the structure factors have been deposited with the RCSB Protein Data Bank under the codes 4ca5, 4ca6, 4ca7 and 4ca8.
Acknowledgements This work was supported by the  Medical Research Council (UK)  through a project grant (number  81272 ) and the  Wellcome Trust (UK)  equipment grant (number  088464 ) to K. R. A. We thank the scientists at stations I02, I03, I04, I04-1 of the  Diamond Light Source, Didcot, Oxon (UK) , for their support during X-ray diffraction data collection.
aegypti genome assembly (AaegL 1. 1 annotation) using TAGMATCHER, a software program based on the short sequence mapping algorithm 'agrep'  (Wu and Manber 1992). TAGMATCHER makes it possible to match tags to a reference genome with errors and multiple matching loci (available on request from eric. coissac@inrialpes. fr). The mapping procedure only retained tags with no ambiguous nucleotides which mapped with a 0 or 1 mismatch at a unique genomic location  (Paris et al. 2012). SNPs with a minimum read coverage of 10, present in at least two different reads (as recommended by  Ingman and Gyllensten 2009)  and showing a minimum allelic frequency of 1%, were called with the samtool mpileup program  (Li et al. 2009 ) and kept for further analyses. F st values were then estimated for each SNP using the PoPoola-tion2 program, which provides several tools for population genetic analyses of NGS pooled data  (Futschik and Schlotterer 2010; Kofler et al.
Genotyping was performed at the Genotyping Center GENTYANE in Clermont-Ferrand, France http://www. ibisa. net/plateformes/GENTYANE,101. html) according to the standard protocol for the DNA Illumina GoldenGate â array  (Fan et al. 2006) , and data were analysed using the software program Genome Studio â v. 1. 5. 10 (Illumina Corporation). The clustering of genotypic classes was manually adjusted when necessary. To ensure the reliability of the genotyping data, we used GenCall50 (GC50), which indicates the reliability of each genotype call, GenTrain, which measures SNP cluster quality, and the call rate (CR), which represents the fraction of 58 samples successfully genotyped for a given SNP. We kept SNPs with GC50 higher than 0. 35, GenTrain higher than 0. 50 and CR higher than 0. 50. For SNPs with <10% missing data (283 SNPs), the concordance between allelic frequencies obtained by cDNA tag sequencing and SNP genotyping was tested for the LiTOX strain using a Pearson's correlation using the 'stat' package in the R software version 2.
Candidate gene identification, sequencing and neutrality tests Candidate genes for Bti resistance were identified using a keyword search in the VectorBase database http://aaegypti. vectorbase. org/index. php. A total of 162 genes belonging to families of toxin receptors (14 alkaline phosphatases, 23 aminopeptidases, 17 cadherins and 20 alpha-amylases) and enzymes involved in toxin activation (six chymotrypsins and 82 trypsins) previously shown to be potentially involved in Bti resistance were considered as candidates. These candidate genes were dispersed over 94 supercontigs in the Ae. aegypti genome. The three aminopeptidases (VectorBase Gene ID AAEL007892, AAEL004738 and AAEL008155) identified in a region showing a signature of selection were sequenced for at least nine susceptible and LiTOX individuals.
We also sequenced as a negative control three candidate genes described in literature as binding Cry toxins (the aminopeptidase AAEL012778, the cadherin AAEL007488 and the alkaline phosphatase AAEL009077;  Chen et al. 2009; Likitvivatanavong et al. 2011b ) but located in genomic regions with low F st between the susceptible and resistant strains, and the aminopeptidase AAEL004226 located more than 1 million bp from an outlier. The complete sequence for each candidate gene was downloaded from VectorBase, and primers amplifying about 1000 bp (range 669-1036) were designed in each gene using the software package Lasergene 7. 2 (DNASTAR Inc. , Madison, WI, USA) (Table  S2 ). DNA amplification was performed in 25 lL total volume with 2 mM MgCl 2 , 0. 1 mM of each dNTP (Roche Diagnostics, Basel, Switzerland), 0.
2 lM of each primer, 5 lg BSA, 0. 6 U AmpliTaq Gold DNA polymerase (Applied Biosystems, Foster City, CA, USA) and 50 ng DNA. The PCR program was initial 10 min denaturation step at 95°C; 40 cycles of denaturation at 95°C for 45 s, annealing at 58°C for 45 s and elongation at 72°C for 60 s; and a final extension step at 72°C for 5 min. Sequences performed by Genoscreen (www. genoscreen. fr) were aligned and corrected using the program Bioedit. Haplotype phase was inferred, and genetic diversity and differentiation analyses (nucleotide diversity p, haplotype diversity H d , number of segregating sites S, number of singletons S i , Watterson's mutation parameter h W , average number of nucleotide differences K within and between strains) were performed using the software DNASP 5. 0  (Librado and Rozas 2009).
Acknowledgements This study was supported by grants from the  R egion Rhône-Alpes  (grant # 0501545401 ), the  French National Research Agency  (grant  ANR-08-CES-006-01 DIBBECO ), the  French Agency for Environmental Health and Safety  ( 2007-CRD-55 ) and the  Institut de Recherche pour le Developpement. We thank the staff of the  Mosquito Control Centre of Martinique  for help with mosquito sampling,  Sylvie Veyrenc  for help with mosquito breeding and  Benoit Villain  for help in the laboratory. We thank  Charles Poncet  and  Lydia Jaffrelo  at the genotyping platform  GENTYANE  ( INRA Clermont-Ferrand, France ) for mosquito genotyping.
As shown in Figure  4 , gene expression was strongly inhibited by MuV-V, whereas TioV-V, TioV-P or TioV-W had no effect. Altogether, we demonstrated that in contrast to MuV-V, TioV-V or known products of the P gene like TioV-P and TioV-W are unable to block IFN-a/b signaling in human cells. This suggested that TioV-V is deficient for targeting specific cellular proteins, in particular host factors involved in IFN-a/b signaling events. TioV-V and MuV-V both Interact with Human MDA5, LGP2 and STAT3 The functional study described above was performed in parallel to a detailed analysis of TioV-V interaction profile with cellular proteins. First, TioV-V was used as bait in the yeast two-hybrid system to screen a human spleen cDNA library. The screen was performed at saturation with a 10-fold coverage of the library (50610 6 diploids), and positive yeast colonies growing on selective medium were analyzed by PCR and sequencing to identify binding partners of TioV-V (data not shown).
Using this protocol, we identified MDA5, LGP2 and STAT3 as direct interactors of TioV-V. The interactions with MDA5 and LGP2 were previously (B) Luciferase expression was determined at 24 h and 48 h post-infection. (C) Culture supernatants from (B) were collected at 48 h post-infection, clarified by centrifugation, UV-inactivated and added to culture wells containing STING-37 cells. Alternatively, culture medium was supplemented with increasing doses of recombinant IFN-b. After 24 h, luciferase expression was determined. Luciferase activity in culture supernatants from (B) was below 1,400 luciferase activity units (data not shown). Experiment was performed in triplicates, and data represent means 6 SD. *indicates that differences observed between MeV and TioV-infected cells were statistically significant (p-value ,0.
All experiments were performed in triplicates, and data represent means 6 SD. *indicates that differences observed relative to controls (none) with IFN-b, IL-6, MDA5 or IFN-l were statistically significant (p-value,0. 01). doi:10. 1371/journal. pone. 0053881. g003 DDB1. After 48 h, viral proteins were purified with glutathionsepharose beads, and 3xFLAG-tagged DDB1 was revealed by western-blot analysis. As shown in Figure  6A , human DDB1 interacted with MuV-V and TioV-V, suggesting that both viral proteins can recruit the E3 ubiquitin ligase machinery in human cells. To further establish the specificity of this interaction, we determined DDB1 binding either to TioV-W or TioV-VCT as described above. In agreement with structural data showing that DDB1 binding peptide is localized within the N-terminal region of PIV5-V  [33, 34] , TioV-V and TioV-W but not TioV-VCT interacted with this cellular factor (Figure  6B ).
We then investigated the induction of STAT1 degradation and the binding of TioV-V or MuV-V to endogenous STAT2. HEK-293T cells were transfected with expression vectors encoding for 3xFLAG-tagged TioV-V, TioV-P, TioV-W or MuV-V, and. Expression of IFN-inducible genes is impaired by MuV-V but not TioV-V expression. HEK-293T cells were transfected with pCIneo-3xFLAG expression vectors encoding for 3xFLAG alone or fused to TioV-V, MuV-V, TioV-P or TioV-W (500 ng/well). 24 h after transfection, cells were left unstimulated or stimulated with 200 IU/ml of recombinant IFN-b. After 24 h of culture, total RNAs were extracted, and expression levels of indicated genes were quantified by qRT-PCR. For each gene, data were normalized so that 100% corresponds to cells transfected with pCI-neo-3xFLAG empty vector and stimulated with recombinant IFN-b (dotted red line).
Experiment was performed twice and data represent means 6 SD. *indicates that differences observed with MuV-V relative to controls cells transfected with 3xFLAG alone and stimulated with IFN-b were statistically significant (p-value,0. 05). doi:10. 1371/journal. pone. 0053881. g004 endogenous STAT1 expression was determined by western-blot analysis at 48 h post-transfection. Results showed that MuV-V efficiently induced STAT1 degradation whereas TioV-V, alike TioV-P or TioV-W, had no effect (Figure  7D ). To determine TioV-V binding to endogenous STAT2, HEK-293T cells were transfected with expression vectors encoding for 3xFLAG-tagged TioV-V, MuV-V or CHIKV-nsp4, and tagged viral proteins were immunoprecipitated with anti-FLAG antibodies conjugated to sepharose beads. Endogenous STAT2 was found to co-immunoprecipitate with MuV-V but not TioV-V or control protein nsP4 (Figure  7E ).
From total RNA extracts, we were able to amplify, clone and establish the sequence of STAT2 from P. rodricensis ( Pr STAT2). A draft of Pteropus vampyrus genome has also been established by the Human Genome Sequencing Center, the Baylor College of Medicine and the Broad Institute, and is available on Ensembl database. A prediction for STAT2 sequence of this species is provided ( Pv STAT2; ENSPVAP00000007175), but required some improvements because sequencing coverage, accuracy, and gene structure annotation were imperfect. We used our data from P. rodricensis together with human and other mammalian sequences to correct and improve the current prediction for Pv STAT2 (see Material and Methods). As shown in Figure  S1 , Pr STAT2 and Pv STAT2 were almost identical, suggesting that STAT2 sequence is highly conserved among giant fruit bats of Pteropus genus.
Plasmid DNA Constructs TioV-V (NP_665866), TioV-P (NP_665865), TioV-W (NP_665867), TioV-VCT (AA 150-228 of TioV-V), MuV-V (ABG48763, Mumps virus isolate ''Sophie'', GenBank accession number: DQ660370) and NiV-V (NP_112023. 1) coding sequences were amplified by RT-PCR (Titan One tube; Roche) from RNA samples kindly provided by Dr. TF Wild, and cloned into pDONR207 (Invitrogen) using an in vitro recombination-based cloning system (Gateway system; Invitrogen) as previously described  [30]. Chikungunya virus (CHIKV) nsP4 construct was previously described  [30]. Corresponding constructs were stored in ViralORFeome database under reference IDs 493, 768, 842, 819, 217, 840 and 716 for MuV-V, TioV-V, TioV-P, TioV-W, TioV-VCT, NiV-V and CHIKV-nsP4, respectively. Compared to reference sequences in GenBank, TioV-P and TioV-W sequences from TioV strain used in this study showed amino acid mutations at positions N182S/A202V and M182V/R202W, respectively.
Yves Jacob). DNA fragment encoding for Pr STAT2 was generated from total RNA purified from Pteropus rodricensis blood. Samples were obtained as part of a routine medical check up performed on animals of a bat colony maintained in La Palmyre zoo. Blood samples were collected by the veterinarian in charge following appropriate guidelines to minimize animal stress and suffering. Bats were anesthetized prior to be handled using a mask with isoflurane at 5% for induction and at 3% for maintenance. Blood was taken from the median vein with a 23G needle. Total RNA were purified using the RNeasy Protect Animal Blood Kit (Qiagen), transcribed into cDNA by RT-PCR, and then cloned in pDONR207 vector. Once established and deposited in GenBank (ID: JQ846265), Pr STAT2 sequence was aligned and compared to Pv STAT2 (Figure  S1 ) sequence prediction available on Ensembl database (ENSPVAP00000007175).
After 48 h, relative luciferase activity was determined. (D) Experiment was performed as in (A), but cells were co-transfected with expression vectors encoding 3xFLAG-tagged TioV-P or TioV-W. (E) Experiment was performed as in (A), but cells were co-transfected with pCI-neo expression vector, either empty or encoding untagged MuV-V, TioV-V, TioV-P or TioV-W. (F) Experiment was performed as in (A), but cells were stimulated with recombinant IFN-l1 at 50 ng/ml. All experiments were performed in triplicates, and data represent means 6 SD. *indicates that differences observed relative to controls (none) with IFN-b, IL-6, MDA5 or IFN-l were statistically significant (p-value,0. 01). doi:10. 1371/journal. pone. 0053881. g003.