dataesr/scientific-paragraphs-categorization huggingface dataset:
The first 30 frames collected during the first minutes of the elution flow were averaged to account for buffer scattering. The 10 frames corresponding to the top of the elution peak were averaged and used for data processing after baseline subtraction. The model of apo NprR(ÁHTH) was built using DaDiModO, a program for refining structures of multidomain proteins against small-angle scattering data  (42). Starting from the type II dimer of the NprR(ÁHTH)/ NprX complex, a more elongated model fitting the experimental data was obtained by introducing flexibility in the a3-a4 loop of TPR2 as well as in the N-and C-terminal extremities. Stepwise generic conformational changes were applied cyclically in a stochastic optimization algorithm that performs a search in the protein conformation space.
DISCUSSION Our study demonstrates that signaling peptide binding shifts the inactive apo dimer of NprR toward an active tetrameric NprR/NprX complex. In the tetrameric conformation, the N-terminal extremities of two adjacent NprR(ÁHTH) subunits are distant of $34 A ˚. S2 ) is expressed in units of ß-galactosidase per milligram of protein (Miller units). Time zero was defined as the onset of the stationary phase. This corresponds to the distance between two half sites of a B-type DNA target. In the absence of an NprR/NprX/ DNA crystal structure, a hypothetical model was built by juxtaposing to the NprR(ÁHTH)/NprX complex two DNA-bound HTH dimers from the recently solved structure of the complex (PDB ID 3U3W) (43) (Figure  6 ). In this model, the two DNA-binding domains of the protein are positioned at opposite ends of the tetramer, in a manner similar to the one shown for the PrgX/pheromone complex  (20).
In this conformation (PDB ID 4GYO), the RapJ fold is similar to that observed in the NprR/NprX complex. Both proteins display the same number of TPRs and an rms distance of $2. 5 A ˚over 294 aligned Ca atoms. Similarly, we hypothesized that in the absence of bound peptide, loop a3-a4 of the NprR TPR2 motif could undergo a large conformational change resulting in reorientation of the first TPR motif and of the N-terminal HTH DNA-binding domain. As a consequence, the tetramer would dissociate into two apo dimers displaying altered TPR domains. Our mutagenesis analysis further suggested that the type II interface observed in the tetramer would be conserved in this apo dimer. This hypothesis is supported by SAXS measurements performed with apo NprR(ÁHTH). We compared the experimental data with simulated curves calculated from different models based on the type II dimer of the NprR(ÁHTH)/ NprX complex.
Uncertainty in GDP forecasting Every quarter ≥ 1, the French national bureau of statistics, INSEE (Institut National de la Statistique et des Etudes Economiques http://www. insee. fr/), publishes the growth rate of the French GDP (Gross Domestic Product). Since it involves a huge amount of data that take months to be collected and processed, the computation of the GDP growth rate log(GDP /GDP -1 ) takes a long time (two years). This means that at time , the value log(GDP /GDP -1 ) is actually not known. However, a preliminary value of the growth rate is published 45 days only after the end of the current quarter. This value is called a flash estimate and is the quantity that INSEE forecasters actually try to predict, at least in a first time. As we want to work under the same constraint as the INSEE, we will now focus on the prediction on the flash estimate and let ∆GDP denote this quantity.
CIRCULAR DICHROISM CD experiments were recorded on a Jasco J-815 spectropolarimeter (Easton, MD, USA) equipped with an automatic 6-position Peltier thermostated cell holder. The instrument was calibrated with 10-camphorsulphonic acid. Far-UV CD data were collected in the 182-260 nm range using a 0. 1 mm pathlength cell (Quartz-Suprasil, Hellma UK Ltd, Southend on Sea, UK) at 25 • C ± 0. 1 • C. Spectra were acquired using a continuous scan rate of 100 nm/min and were presented as an average of 25 successive scans. The response time and the bandwidth were 0. 5 sec and 1 nm, respectively. The absorbances of the sample (at a concentration of 28 μM) and buffer were kept as low as possible. Spectra were obtained in 10 mM sodium phosphate buffer at pH 7. 4 with 25 mM NaCl and 1mg/ml of Nvoy polymer.
The spectrum was corrected by subtracting the solvent spectrum obtained under identical conditions. The secondary structure was estimated with the CDPro suite software  (Sreerama and Woody, 2000). A far UV circular dichroism spectrum was used as described  (Kelly et al. , 2005). The spectrum of the AtGIP1 construct has been deposited in the Protein Circular Dichroism Data Bank  (Whitmore et al. , 2011)  (http://pcddb. cryst. bbk. ac. uk) with the accession code CD0004243000 for release upon publication.
After repeated washing with PBS, the sections were then incubated for 2 h with goat-anti-rabbit antibodies coupled to 15 nm colloidal gold particles (Aurion EM Reagents, Wageningen, The Netherlands) followed by washing with PBS and H 2 O. Samples were visualized with a Hitachi H-600 electron microscope operating at 75 kV and Images were captured with a CCD Advantage HR Hamamatsu camera and AMT software (Advanced Microscopy Techniques, Danvers, MA, USA).
ACCESSION NUMBERS Sequence data from this study can be found in the Arabidopsis Genome Initiative or GenBank/EMBL databases under the following accession numbers: Arabidopsis (At) GIP1: At4g09550; AtGIP2: At1g73790; AtTSA1: At1g52410; AtNAI2: At3g15950; At3g15960; AtSUN1: At5g04990. Accession numbers of the sequences used for establishing the phylogenetic tree of GIP peptidic sequences (Figure  1 ) are presented in Table  S2. CD data deposit on the accession number CD0004243000.
AtGIPs ARE α-HELIX PROTEINS CONSERVED IN UNICELLULAR AND MULTICELLULAR ORGANISMS AtGIPs were previously identified as partners of AtGCP3, a member of the γ-TuC  (Janski et al. , 2008). These small proteins have FIGURE 1 | Phylogenetic tree of GIP peptidic sequences. Sequences were aligned using T -coffee and Myers-Miller matrix. A tree was constructed using the neighbor joining algorithm. Analyses were performed using the MacVector software. GIP sequences segregate accordingly to the genus of life evolution. This suggests that GIPs probably originate from one and the same ancestor and that they are not the products of a convergent evolution that would result in a mix of the sequences. Accessions numbers of the used sequences are presented in Table  S2. been identified in numerous organisms, as shown in Figure  1  and Table  S2.
Frontiers in The following sequence-[MILVT] xxx[LV] xxx [LIVT]- [DTS] xxx [LIFVM]xx[CLIAVF]-[ILVME]-x [LMFVA]xxxGxx [PGA], xx [LIV]-[VIAS]x [VILAM]-[VIFLG] -has been established as a GIP signature. Used in database screens, it allowed us to identify GIPs in a large variety of eukaryote species, except S. cerevisae. In the plant kingdom, a GIP gene duplication occurrence was linked to the conquest of terrestrial habitats. AtGIP1, used as a reference, shares 41 to 78% identity with the 115 plant GIP sequences analyzed so far. Aminoacid similarities were mapped between AtGIP1 and AtGIP2 or human GIP (Figure  2A ). GIPs do not harbor any characterized consensus functional domains, except a glycine (Figure  2A , in bold) and repeated leucines, mostly conserved throughout evolution (Figure  2A , stars).
In order to determine the AtGIP1 secondary structure content, we recorded a far UV circular dichroism spectrum. The secondary structure was estimated with the CDPro suite software using CD data of the SP37 reference database (a base of 37 soluble proteins of known secondary structure elements) and the CONTIN method. CONTIN fits the CD of the GIP protein by comparison with a linear combination of the spectra from a large database of proteins with known conformations. This led to 82% for αhelices, 4% for β-sheets and 14% for other secondary structure contents. These results indicate that α-helices mainly constitute AtGIP1 (Figure  2B ). Accordingly, computer modeling predicts that the AtGIP1 3D structure is composed of three α-helices (Figure  2C ). Interestingly, the conserved glycine residue (aa 42 in AtGIPs), found in all organisms except S.
ACKNOWLEDGMENTS This work was supported by the  Centre National de la Recherche Scientifique (CNRS). The microscopy experiments were carried out using devices from the Strasbourg-Esplanade cellular imaging facilities sponsored by the  CNRS , the  Université de Strasbourg , and the  Région Alsace , the  Association de la Recherche sur le Cancer  and the  Ligue Nationale contre le Cancer  (http://ibmp. fr?id=micro). We are grateful to  D. Evans  and  K. Graumann  for providing us with the anti-AtSUN1 antibody as well as the Agrobacterium strain expressing the 35S:: AtSUN1-YFP  and we thank  Pr. Suzuki  for providing the AtTSA1 gateway vector and.
Decorin is overexpressed in muscle-invasive as compared to non-muscle-invasive human bladder carcinoma To determine whether decorin could also participate in development of human invasive bladder tumours, we next quantified decorin (DCN) mRNA expression level in our set of 162 tumour and 4 normal samples using Affymetrix U133 plus2. 0 microarrays  (Fig 6A). A significant overexpression of decorin was observed in the muscle-invasive bladder carcinoma (MIBC) (>pT2) as compared to superficial/non-muscle invasive bladder carcinoma (NMIBC) (pTa or pT1) and to normal urothelium  (Fig 6A). These data were confirmed using another type of microarray (Affymetrix exon 1. 0st) to analyse the same set of tumours (Supporting Information Fig  S5A ), but also by analysing publicly available transcriptomic datasets from three independent series of MIBC and NMIBC  (Lindgren et al, 2010; Riester et al, 2012; Sanchez-Carbayo et al, 2006)   (Supporting Information Fig S5B).
In our dataset, there was no correlation between DCN expression and DNA copy number at the DCN locus, suggesting a transcriptional deregulation in tumours  (Supporting Information Fig S6). DCN expression is mostly described as correlated to myofibroblast and fibroblast extent  (Hocking et al, 1998). To determine if DCN overexpression observed in MIBC was only due to an increased infiltration of myofibroblasts within the tumour during tumour progression, we took advantage of the human protein atlas portal (http://www. proteinatlas. org/) 3 Figure  3. MB49-I is not recognized by H-Y antigen-specific T cells. A. Proliferation of transferred H-Y-specific CD4 þ and CD8 þ T lymphocytes was analysed in female CD45. 1 þ C57Bl/6J mice 6 days after footpad injection of MB49 or MB49-I cells, or PBS (control).
Gene ontology biological process enrichment was also evaluated using the Gorilla application, which allows 'tree' visualization  (Eden et al, 2007; Eden et al, 2009)   S1  and S2 ). DCN expression in MIBC were determined using Pearson's correlation (p < 1. 10 À6 and R > 0. 5) (Supporting Information Table  S1 ). Significant enrichment of genes related to physiological pathways (italics) and gene ontology annotations relative to biological process within genes positively regulated with DCN were determined by DAVID software (corrected p-value < 0. 01 and corrected p-value < 0. 001, respectively) (Supporting Information Tables  S1  and S2 ). All these pathways and gene ontology annotations, except one, can be grouped into four known functions of decorin. CD45. 2 þ Vb6 þ CD4 þ (Marilyn) or Vb8 þ CD8 þ (MataHari) secretion of the protein in vitro (Fig 7B ).
This observation could explain the discrepancy between our study and a previous report showing downregulation of DCN expression in human bladder carcinoma  (Iozzo et al, 2011). In this other study, bladder tumours were compared to whole bladder or bladder mucosa, which contain stroma and smooth muscle cells from the bladder wall in addition to urothelium. Of note, however, when comparing muscleinvasive to superficial tumours, the authors observed, like us, overexpression of decorin in MIBC. Interestingly, using our exon array data for bladder wall muscle, normal urothelium and bladder tumours, we observed that DCN was transcribed from at least two promoter regions in bladder tissues. In muscle tissues, DCN appears to be preferentially transcribed from a promoter that is not expressed in normal and tumoural tissues.
One of the few examples of successful immunotherapy is the treatment of NMIBC by BCG. However, in MIBC, BCG is not effective and surgery, chemotherapy and radiotherapy are the main treatments used in these settings. Our observation that tumour antigens are lost during progression of bladder tumours could explain, at least partly, the failure of efficient induction of anti-tumour immune responses by BCG in MIBC. Finally, our data demonstrate that decorin is associated with progression and promotes invasiveness in human bladder cancer, as proposed from our analysis of a mouse invasive bladder tumour cell variant. Decorin may thus offer the potential for therapeutic exploitation in advanced bladder cancer.
Analysis of H-Y antigen expression and Y chromosome presence RNA was extracted from MB49, MB49-I and male splenocytes using Qiagen Rneasy kit (Qiagen) and reverse-transcription were performed on 1 mg of RNA with AMV-RT (Finnzyme, Esposo, Finland). Expression of the two H-Y antigens Uty and Dby was measured by quantitative RT-PCR on a Lightcycler LC480 (Roche) using Taqman primer pairs and probes for quantitative real-time PCR from Applied Biosystems (Genbank accession numbers in parentheses; assay identification numbers from Applied Biosystems provided here): Uty (NM_009484. 2), Mm00447710_m1; Dby (NM_012008. 2), Mm00465349_m1; Gadph (NM_008084. 2), Mm99999915_g1. Cycle threshold (Ct) for mouse Uty and Dby were normalized to Ct for Gapdh and results were expressed as arbitrary units (AU: 2 Ct(Gapdh)-Ct(gene) Â 1000).
Analyses of human bladder samples and Affymetrix microarray data A set of human bladder carcinomas was collected from patients treated surgically between 1988 and 2006 at Henri Mondor Hospital (Créteil, France), Institut Gustave Roussy (Villejuif, France) and Foch Hospital (Suresnes, France). All tumours were pathologically reviewed, staged according to the 2009 TNM. All patients provided written informed consent and the study was approved by the ethics committees of the various hospitals. Normal urothelial samples were obtained from organ donors (Diez de Medina et al, 1997), Expression of desmin, a specific smooth muscle cell marker, was measured by RT-qPCR, and tumour samples with expression higher than 25% of the median of 5 normal bladder smooth muscle were considered over-contaminated with stroma, and thus not included in the analysis.
Human bladder samples were analysed with Affymetrix HG-U133 Plus 2. 0. Data for DCN and DCN-correlated genes among MIBC (pearson R > 0. 5) are available for 162 tumours and 4 normal urothelium (Supporting Information Table  S3 ). The microarray data described here are available from ArrayExpress (www. ebi. ac. uk/ arrayexpress/) under the accession numbers E-MTAB-1803 for the muscle invasive bladder tumours and E-MTAB-1940 for the nonmuscle invasive tumours and normal samples. Twenty-five bladder cancer derived cell lines were obtained from ATCC or DSMZ. RNA, DNA and proteins were extracted from frozen human bladder samples and from human bladder cancer cell lines grown to 70% confluence, by centrifugation through a cesium chloride density gradient. Cell lines were analysed with Affymetrix Exon1.
Publicly available gene expression datasets Three independent datasets of human bladder tumours were used:  (Riester et al, 2012 ) (GSE31684) containing data obtained using Affymetrix HG-U133 Plus 2. 0 array for 93 bladder tumours,  (Lindgren et al, 2010 ) (GSE19915) containing data obtained from cDNA microarray for 144 bladder tumours, and  (Sanchez-Carbayo et al, 2006)  containing data obtained using Affymetrix U133A array for 105 bladder tumours. Gene expressions (Affymetrix U133 plus 2. 0) for 22 bladder cancer-derived cell lines were downloaded from the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE, www. broadinstitute. org/ccle).
Plates were taken out and 75 ml of medium-1% FCS containing 4. 10 4 cells were loaded in each well. Plates were placed back in the xCELLigence device, which was set to measure impedance every 5 min for the next 72 h. Data were plotted using the RTCA software as cell index (CI) value over time, and the slope of CI between 0 and 24 h (TCCSUP) or 0 and 36 h (MB49/MB49-I) was chosen as the shortest time point showing high enough CI.
Statistical analyses Experiments were performed in mice at least 2 and up to 7 times, amounting to between 4 and up to 31 individual samples. In human studies, a total of 162 individual tumours were analysed. In most figures, results are represented as individual dots corresponding to individual samples. Mann-Whitney test was used to compare tumour growth, percentages of immune cells in groups of mouse tumours and quantitative RT-PCR data, using Prism 4. 0 software. p-values less than 0. 05 were considered statistically different.
org/). Immunolabelling of decorin was performed using two different antibodies showing the same localization of decorin. C. Pathways and gene ontology biological processes significantly enriched within genes positively correlated with DCN in human MIBC. Genes correlated withDCN expression in MIBC were determined using Pearson's correlation (p < 1. 10 À6 and R > 0. 5) (Supporting Information TableS1). Significant enrichment of genes related to physiological pathways (italics) and gene ontology annotations relative to biological process within genes positively regulated with DCN were determined by DAVID software (corrected p-value < 0. 01 and corrected p-value < 0. 001, respectively) (Supporting Information TablesS1 and S2). All these pathways and gene ontology annotations, except one, can be grouped into four known functions of decorin.
Acknowledgements This work was supported by  INSERM, Institut Curie  and by grants from  Fondation de France  (to CT),  INCa  ( INCA_5975  to CT, OL and FR),  La Ligue Nationale Contre le Cancer  (FR: équipe labellisée; OL: équipe labellisée), and the program " Carte d'Identité des Tumeurs ", initiated, developed and funded by  Ligue Nationale Contre le Cancer. MEB was a fellow from  Fondation pour la Recherche Médicale. We thank  P. Le Baccon  ( CNRS UMR218 ,  Institut Curie ) for help to analyse FISH experiments,  Remy Nicolle  for help to analyse next generation sequencing data, and  Christel Goudot  for help with the R software. We acknowledge excellent help from the  Animal Facility of Institut Curie.
proteinatlas. org/). Immunolabelling of decorin was performed using two different antibodies showing the same localization of decorin. C. Pathways and gene ontology biological processes significantly enriched within genes positively correlated with DCN in human MIBC. Genes correlated withDCN expression in MIBC were determined using Pearson's correlation (p < 1. 10 À6 and R > 0. 5) (Supporting Information TableS1). Significant enrichment of genes related to physiological pathways (italics) and gene ontology annotations relative to biological process within genes positively regulated with DCN were determined by DAVID software (corrected p-value < 0. 01 and corrected p-value < 0. 001, respectively) (Supporting Information TablesS1 and S2). All these pathways and gene ontology annotations, except one, can be grouped into four known functions of decorin.
Study population and setting This study was reviewed and approved by the Research Ethics Committee of King Faisal Specialist Hospital and Research Centre. The study utilized only clinical isolates with anonymized data collection and analysis, hence a waiver for consent forms was provided. During July 2009 through June 2011, all the available non-repetitive M. tuberculosis complex isolates were enrolled into the study from the province. The isolate culturing and data collection were carried out in central tuberculosis reference laboratory of the Eastern province. This study utilized 77 drug resistant isolates collected from the province as part of another recently published nationwide study conducted at the same time  [17]. The study population was divided into two major groups "Immigrants" and "Autochthonous" population (Saudi nationals, abbreviated as SA).
Data Analysis The drug susceptibility results were classified as sensitive (no resistance), mono (resistance to a single drug), poly (resistance to more than one drug, other than both rifampicin and isoniazid) and multi drug resistant tuberculosis (MDRTB) (resistance to both rifampicin and isoniazid). The spoligotyping results were converted into octal codes. Mycobacterial genetic lineages were identified using MIRU-VNTR and spoligotyping data and the online tools available on MIRU-VNTR Plus and SITVIT web sites (www. miru-vntrplus. org & http://www. pasteurguadeloupe. fr:8081/SITVIT_ONLINE/index. jsp) according to the previously described strategy, combining best-match and phylogenetic tree-based analysis  [20, 21]. Molecular clustering of the isolates was determined by constructing a dendogram based on spoligotyping and MIRU-VNTR data, using the unweighted pair group method using average linkages and the categorical coefficient.
Distribution of phylogeographical lineages Genotyping identified a total of 13 lineages, dominated overall by Delhi/CAS (29. 4%), EAI (23. 8%), Ghana (13. 3%) and Haarlem (8. 6%) lineages (Dataset S1). The isolates from autochthonous population showed a predominance of Delhi/CAS (33. 3%) followed by Ghana (14. 3%) and EAI (13. 3%). On the other hand, the immigrant cases showed a prevalence of EAI (30. 9%), followed by Delhi/CAS (26. 7%) and Ghana (12. 7%) lineages respectively. The lineage Beijing was found to be 8. 6 % and 5. 2 % among immigrant and Saudi cases, respectively. Noticeably, the lineage TUR and undefined strains were found only among Saudi nationals (Table  2 ).
1 Study Groups (Case/Percentage) Geographical origin of immigrants Total (N=524) Saudi (N=210) Non-Saudi (N=314) South Asia South East Asia Africa West Asia Delhi/CAS 154 (29. 4) 70 (33. 3) 84 (26. 7) 71 10 2 1 EAI 125 (23. 8) 28 (13. 3) 97 (30. 9) 52 39 4 2 Ghana 70 (13. 3) 30 (14. 3) 40 (12. 7) 19 7 3 11 Haarlem 45 (8. 6) 24 (11. 4) 21 (6. 7) 9 12 Beijing 38 (7. 2) 11 (5. 2) 27(8. 6) 12 14 1 LAM 26 (5. 0) 15 (7. 1) 11 (3. 5) 4 5 1 1 S 17 (3. 2) 9 (4. 3) 8 (2. 6) 5 3 Uganda-I 12 (2. 3) 9 (4. 3) 3 (1. 0) 2 1 URAL 11 (2. 1) 6 (2. 8) 5 (1. 6) 3 1 1 New-I 10 (1. 9) 2 (0. 9) 8 (2. 5) 5 3 X 7 (1. 3) 1 (0. 5) 6 (1. 9) 3 1 2 Cameroon 4 (0. 8) 4 (1. 3) 2 2 TUR 3 (0. 6) 3 (1. 4) Unknown 2 (0. 4) 2 (0. 9) 1. Lineages assigned based on the MIRU-VNTR plus online database, number of lineages among the study group Non-Saudi showed as numbers.
The DSSZ modifications are rather small, leading to a suppression similar to the one assuming energy loss effects only. On the contrary, the EPS09 set exhibits larger modifications to the gluon nPDF (and in particular a slightly faster variation in this x domain) increasing the slope of R J/ψ dAu versus y. At mid-and forward rapidity, the various predictions are similar; in particular all of them reproduce nicely the data at y = 1-2 with a slightly better description with saturation or using the EPS09 set as compared to DSSZ (yet this is not statistically significant). On the other hand, the predictions are different at backward rapidity. The best agreement is obtained assuming saturation effects (in addition to parton energy loss) or DSSZ nPDF instead of EPS09. This observation obviously depends on the present energy loss model, preventing us from drawing a firmer conclusion.