dataesr/scientific-paragraphs-categorization huggingface dataset:
S. aureus has a genome markedly more A+T-rich (67. 2%) than B. subtilis (56. 5%) and E. coli (49. 2%). We therefore wanted to examine to what extent different genome compositions may lead to a different rate of random occurrence of the TATAAT hexamer that corresponds to the canonical core of the -10 box for the housekeeping sigma factor (SigA in S. aureus and B. subtilis, Sig70 in E. coli) in the three genomes (GenBank: CP000253, AL009126. 3, U00096. 3). The TATAAT hexamer was indeed much more frequent (0. 905 Kbp -1 ) in the antisense strand of protein-coding genes in the S. aureus genome than in the B. subtilis (0. 332 Kbp -1 ) or E. coli genome (0. 091 Kbp -1 ). In each of these three genomes the TATAAT hexamer was also less frequent on the sense strand than on the antisense strand (e. g.
RNA preparation and tiling array hybridization Total RNA was prepared by acid-phenol extraction after mechanical cell disruption as described previously  [13]. The tiling array used in this study contains 383,452 probes covering both strands of the S. aureus NCTC 8325 genome with a tiling step of 18 nucleotides  [113]. Synthesis and hybridization of labeled cDNA were carried out at Roche NimbleGen (Madison, WI) using the strand-specific method described before  [114]. All experiments were performed in triplicate with RNA isolated from independent cultures. Tiling array data have been deposited in the NCBI's Gene Expression Omnibus (GEO) database (accession numbers GSE70040-43).
The precision in the mapping of upshifts was determined previously  [13]  by a comparison of the up-shift positions detected in B. subtilis with transcription start sites mapped by a differential RNA-seq approach  [118] , which revealed that the resolution is within the range of the tiling step with a tendency to have upshifts slightly upstream (median of 12 bp in B. subtilis) of the actual transcription start site. New transcripts (i. e. unannotated in GenBank: CP000253) were detected where the lower boundary of the 95% equal-tailed credibility interval for the smoothed trajectory reached 10-fold the chromosome median. These segments were further split according to breakpoints to avoid aggregation of regions with different transcription levels and extended on their 5' and 3' extremities according to a more permissive expression cut-off (5-fold the chromosome median) to avoid over-segmentation in regions with expression levels close to the 10-fold cutoff.
Sequence analysis of transcript 5'-ends and 3'-ends The classification of promoters based on the presence of sigma factor binding site motifs around the up-shifts (-60bp, +40bp) was performed with the software 'treemm'  [13]  that also takes into account expression profiles across hybridizations. This analysis allowed positioning of the sigma factor binding sites with bp-level resolution. Other transcription factor binding sites (TFBS) were searched with MAST v4. 9. 0  [119]  using position weight matrices built from known binding sites. For this purpose, we retrieved from the RegPrecise database v2. 1  [68]  the manually curated binding sites across Staphylococcaceae for the transcription factors listed for S. aureus N315. For WalR and GraR, not present in RegPrecise, we used the binding sites listed in  [113, 120, 121].
The resulting position weight matrices were used as queries in MAST searches against the database of the sequences around the up-shifts (-100bp, +50bp; E-value cut-off 1). In keeping with the orientations of binding sites listed for S. aureus in RegPrecise we considered only the occurrences with the same orientation as the up-shifts, except for WalR for which we took both strands into account. We compared the position of signal down-shifts to predictions of intrinsic terminators available at http://transterm. cbcb. umd. edu/tt/ that were made from the sequence alone with the software TranstermHP  [48].
Two categories of intergenic regions are distinguished: intra (dark blue) for strictly intracistronic regions, and inter (light blue) for regions where the downstream gene can be transcribed from its own promoter. Finally, depending of the presence or absence of a defined termination site, independent segments decompose into two categories: indep (black) and indep-NT (brown). Transcription segments overlapping (100bp or 50%) GenBank annotated genes on the opposite strand are referred to as antisense (AS).
This work was supported by  CEU  projects  LSHG-CT-2006-037469  (BaSysBio) and  LSHM-CT-2006-019064  (StaphDynamics); the  Top Institute Pharma  projects  T4-213  and  T4-502 ; the  Institut Pasteur ;  CNRS ; the  ANR  projects  ANR-08-ALIA-0011   NABAB  and  ANR-09-MIEN-0010  GRABIRON; the outside the human body.
b Regions defined from positions up-regulated in at least one of the four experimental conditions (RPMI exp, RPMI t4, TSB exp, TSB t4). c Cumulated length. d Maximum length. e Fraction of regions overlapping GenBank annotated genes and new expression segments detected in the wild-type. f Fraction of regions antisense to GenBank annotations. g Number of regions of which the first 200 bp overlap with a gene up-regulated in the Δrho mutant (annotated gene or new segment of categories 5', indep, and indep-NT).
Case selection We included 75 consecutive sCJD cases from the collection of the Austrian Reference Centre for Human Prion diseases, where all areas for the full state-of-the-art characterization of different neurodegenerative disorders were available  (38). For comparison of the complex tauopathy seen in a subset of sCJD cases, we included three cases (two from France and one from Austria) with the V203I mutation of the PRNP gene. Genetic analysis was performed using genomic DNA isolated from blood samples or frozen brain tissue as published before in the frame of CJD surveillance  (46). Human biological samples and associated data were obtained from the CJD Surveillance and KIN-Biobank Medical University of Vienna (Ethics Committee approval: 396/2011) and the Cardiobiotec Biobank (CRB-HCL Hospices Civils de Lyon BB-0033-00046).
This observation has important implications for the application of this epitope for dementia diagnostics. In particular, pTau epitopes vary considerably even during the same disease process  (35). Thus, depending on the tau pathological process (neuronal or glial predominant or mixed forms)  (34) , CSF pTau examination with a single epitope marker might not reflect the whole spectrum of alterations. Tau in CSF occurs as a series of fragments; discrimination of AD from controls is dependent on the subset of tau species measured  (49). There are studies examining further epitopes (eg, T231) (3, 7), which we evaluated here, however, there is a relative paucity on data on their reliability and reproducibility. Indeed, CSF and brain pTau patterns have not been compared systematically. More pTau epitopes should be measured in the CSF to reflect better the spectrum of tau pathologies in the brain.
ACKNOWLEDGMENTS The Austrian Reference Centre for Human Prion Diseases is supported by the  Federal Ministry of Health ,  Austria. Cardiobiotec  is authorized by the  French Ministry of Social Affairs and Health  ( DC2011-1437 ) with transfer authorization ( AC 2013-1867 ). P. P. L. and B. S are supported by the  Healthy Ageing Research Centre project  ( REGPOT-2012-2013-1 ,  7FP ). P. P. L. , B. S. and G. G. K. are supported by  € OAD Austria-Poland  ( PL 04/2014 ).
Patients We reviewed 82 cases of PL diagnosed between 2008 and 2014, collected from 42,145 samples registered in Lymphopath, a government-supported network of expert hematopathologists which conducts a systematic review of all newly diagnosed or suspected lymphomas in France. 27, 28 The diagnosis of PL was based on histological criteria and the expression of plasma cell differentiation markers as described by the WHO classification. 2 Patients with a prior diagnosis of plasma cell myeloma or with multiple bone lesions or other laboratory criteria supporting the diagnosis of myeloma were excluded from the study. The following data were collected: age, sex, disease location at presentation, an associated context of immunodeficiency (HIV infection, transplantation, autoimmune disease, immunosuppressive drugs), EBV serology, Ann Arbor staging, treatment and outcome, current status and date of last follow up.
Statistical analysis Comparison of clinicopathological, immunological, and genetic features between EBV -and EBV + patients was carried out using c 2 test (or Fisher exact test when required). Event-free survival was determined from time of diagnosis until time of death, progression or last follow up. Survival curves were constructed by the Kaplan-Meier method. Survival distributions were compared with the log rank test. For co-variates with less than 20% of missing values and with a P-value<0. 05 in the log rank test, Cox proportional hazards model was performed. Using a backward stepwise removal method, only significant covariates were kept in the final Cox model. Statistical significance was set at P=0. 05. Analyses were performed using GraphPrism and STATA v. 13 software.
Acknowledgments We thank  Laurence Jalabert ,  Audray Benest  and  Gabrielle Perez  for immunohistochemistry staining and FISH studies (IUCT, Toulouse, France) and  Marina Bousquet  for reviewing the paper. We thank  François-Xavier Frenois  for whole slide imaging (IUCT Toulouse, France). We thank the  Lymphopath consortium  for sending their samples:  Pr Gaulard  ( Hôpital Henri Mondor, Créteil, France );  Pr J. F. Fléjou  ( Hôpital Saint Antoine, Paris, France );  Pr V. Costes Martineau  ( CHU de Montpellier, France );  Pr A. de Mascarel  et  Dr M. Parrens  ( CHU de Bordeaux, France );  Dr I. Soubeyran  ( Institut Bergonié, Bordeaux, France );  Dr C Chassagne-Clement  ( Centre Léon Bérard, Lyon, France );  Dr L. Xerri  ( Institut Paoli Calmettes, Marseille, France );  Dr A Moreau  ( CHU de Nantes, France );  Dr F.
Patients Patients were eligible if they were over 65 years of age and presented with symptomatic, measurable, newly diagnosed multiple myeloma. Between September 2012 and September 2014, a total of 56 newly diagnosed elderly MM patients were treated in 6 institutions in France. The diagnosis, clinical staging and prognostic score of MM were based on the Durie and Salmon staging system and the International Staging System (ISS). 23, 24 The Seattle group's hematopoietic cell transplantation specific comorbidity index (HCT-CI) was used to score the comorbidities. 25 Baseline demographics, clinical and laboratory data at diagnosis, and information on treatment and response were collected prospectively and recorded in the EBMT Promise (Med B) database. Patients gave their informed consent to the study.
Next generation sequencing (NGS) was performed at Molecular Research DNA (MR DNA -Shallowater, TX, USA) on a MiSeq following the manufacturer's guidelines. Sequence data were processed using MR DNA analysis pipeline (MR DNA, Shallowater, TX, USA). Tissue preparation for histological analysis. Flushed colons were opened longitudinally, cut into 2 cm sections and rolled according to swiss-roll procedure  20. The samples were fixed in 4% paraformaldehyde (24 h, 4 °C), dehydrated, and embedded in paraffin according to standard histological protocols. Four-micrometer sections of distal colon were mounted on SuperFrost ® Plus slides. To assess colonic damage, the sections were stained with hematoxylin/eosin and examined blindly according to the Ameho criteria  21. Cytokine analysis. Before sacrifice, blood samples were obtained from the retro-orbital venous plexus, centrifuged and stored at -80 °C.
Slides were mounted using Fluorescent Mounting Medium (Dako). Tissues were visualized using a microscope Nikon Eclipse Ni-E and the NIS-Elements analysis software (Nikon Instruments Inc. , Melville, NY). The mean of fluorescence intensity (MFI) and the area of colonic tissue (area) of each imagen was measured using Image J Software. A total of four images were considered for each mice. Statistical Analysis. Statistical analysis was completed using GraphPad software (GraphPad Sofware, La Jolla, CA, USA). Results are presented with means ± SEM except for Illumina experiments, median ± SEM. For mice experiments, sensitized (mother-separated) mice displaying VMR values lower than mean minus two standard errors for all distension volumes were considered as non-sensitized and excluded from the analysis (Grubb's Test).
Results Microbiota abundance of F. prausnitzii impacts on colonic hypersensitivity and permeability in a non-inflammatory NMS-induced murine model. Next generation sequencing (NGS) of the 16 S genes were performed by Illumina on fecal samples of NMS mice compared to control non handled (NH) mice, just after weaning (Week 3) and at the CRD period (Week 12), to analyze the composition of the microbiota. At the phylum level, such NGS analysis indicated that the microbiota of NMS mice and control NH mice were quite similar (data not shown). Principal component (PCoA) plots of unweighted UniFrac analysis also demonstrated any significant differences in the species level global composition of NMS mice and control NH mice (data not shown). these results suggest that NMS paradigm did not result in marked alterations of the gut microbiota.
Acknowledgements Authors would like to thank  Jean-Marc Chatel  and  Chantal Bridonneau  for their advices during this work and M2ISH team for their help concerning Claudin-2 experiments. This study was a part of FPARIS collaborative project selected and supported by the  Vitagora Competitive Cluster  and funded by the  French FUI (Fond Unique Interministériel ;  FUI: n°F1010012D ), the  FEDER  ( Fonds Européen de Développement Régional ; Bourgogne:  34606 , and Auvergne:  32025 ), the  Burgundy Region , the  Conseil Général 21 , the  Grand Dijon, ANR VISCERALGY  ( ANR-09-MNPS-037-01 ) and the  Conseil Régional d' Auvergne  ( MHIB grant ). This work was also supported by  Merck Médication Familiale (Dijon, France)  and  Biovitis (Saint Etienne de Chomeil, France).
Number of times this article has been viewed ] [12] [13] [14] [15]  Owing to its uniform expression on malignant cells in HL and sALCL, CD30 has emerged as an attractive target for the treatment of these lymphomas. The antibody-drug conjugate brentuximab vedotin (BV) delivers the potent microtubuledisrupting agent monomethyl auristatin E to CD30-positive cells. 14, 15 Two pivotal Phase II multicenter, open-label trials evaluated the safety and efficacy of BV in patients with relapsed/refractory (R/R) HL (NCT00848926) or sALCL (NCT00866047). 14, 15 BV was associated with manageable toxicity and high objective response rates (75% HL; 86% sALCL). 14, 15 The most common treatment-related adverse events (. 15% in either study) in both studies included peripheral sensory neuropathy, nausea, fatigue, pyrexia, diarrhea, and neutropenia.
Acknowledgments The authors would like to thank  Dana A Kennedy  and  Eric Sievers  ( Seattle Genetics, Inc. ) for their contributions to the study design and conduct, and  Yinghui Wang  ( Seattle Genetics, Inc. ) for statistical guidance. Medical editorial assistance was provided by  Tara Ruest  and  Ann Yeung  ( Scientific Pathways ) with funding from  Seattle Genetics, Inc. Direct funding for this research was provided by  Seattle Genetics, Inc. , through the joint financial support of  Seattle Genetics and Millennium Pharmaceuticals, Inc. , a wholly owned subsidiary of  Takeda Pharmaceutical Company Limited.
15, 16 The 6MST has been used to assess exercise tolerance in the context of PR. 17, 18  However, the correlation between the 6MST and validated indices used to measure exercise capacity (6MWT and CPET) has not yet been established. The primary objective of this study was to analyze the correlations between exercise tolerance data provided by the 6MST, 6MWT, and CPET in a population of COPD patients managed by outpatient PR. The secondary objective was to analyze and compare the course of exercise tolerance measured by 6MST and 6MWT before and after PR.
Material and methods This monocentric retrospective study included COPD patients managed by outpatient PR. Patients included in this study were those who had completed the entire PR program and those for whom pre-rehabilitation 6MWT, 6MST, and CPET assessment data were available. The severity of COPD was evaluated by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. 19 atients were divided into two groups according to GOLD stage: mild-to-moderate COPD (Stages 1 and 2) and severeto-very-severe COPD (Stages 3 and 4). All data were collected prospectively and were entered into our rehabilitation computerized medical records. The study protocol was approved by the Observational Research Protocol Evaluation Committee of the French Language Society of Pulmonology, France. As the study data was collected as part of a pulmonary rehabilitation program prior to this retrospective study commencing the Observational Research Protocol Evaluation Committee advised written informed consent did not need to be obtained from the patients.
Results One hundred seventy-seven COPD patients were managed by outpatient PR between January 2010 and December 2014. Ninety-one (51%) of these patients completed a pre-rehabilitation assessment comprising all three tests (6MST, 6MWT, and CPET) and were included in this study. Another 86 patients (49%) were excluded due to missing CPET (n=39) or 6MWT data (n=21), or because a stress test rather than CPET was performed (n=26). The characteristics of the 91 patients are presented in Table  1. A statistically significant correlation was observed between the number of steps on the 6MST and the distance covered on the 6MWT (r=0. 56; P,0. 0001; Figure  1 ),  independent of the severity of COPD (Table  2 ). This correlation was observed in patients with mild-to-moderate COPD and in patients with severe-to-very-severe COPD (Table  3 ).
The total β-cell volume was analyzed as previously described. 21, 38, 70 Images were captured with an inverted microscope (Nikon Instruments, Amstelveen, The Netherlands) equipped with a Hamamatsu digital camera c10600 (Olympus) or with a multiphoton microscope (LSM710 NLO with a TiSa laser, Zeiss, Thornwood, NY, USA) and analysed using Smartcapture 3 (version 3. 0. 8) NIS AR2. 30 Imaging Software (Nikon France, Champigny-sur-Marne, France) or Improvision Volocity LE (version 5. 0) (PerkinElmer, Waltham, MA, USA) and ImageJ software (https://imagej. nih. gov/ij/). 71 miR375 analysis in plasma. Plasma was obtained from tail vein blood from adult WT and Stat3 -/-mice at D1, D3, D5, D7, D10 and D14 post PDL surgery. Analysis of miR375 was performed as described by Roels et al. 72  (In preparation).
Statistical analysis. Data were analyzed using GraphPad Prism 5 (GraphPad Software, San Diego, CA, USA) and are expressed as mean ± S. E. M. of at least three independent experiments. Data were analyzed by unpaired two-tailed Student's t-test or with one-way or two-way ANOVA with Bonferroni post-hoc test and were considered statistically significant when Po0. 05. To determine the confidence interval for the proportion of P-STAT3 + Ki67 + β-cells, the Wilson score confidence interval was used. Wilson scores have coverage probabilities close to the nominal confidence level, also for small samples sizes or extreme frequencies close to zero.
Acknowledgements. We thank  Dr Bin Gao  ( NIH, Laboratory of Liver Diseases, Bethesda, MA, USA ) for providing STAT3lox:lox mice, and  Ann Demarré ,  Veerle Laurysens ,  Jan De Jonge ,  Erik Quartier  and  Gaby Schoonjans  for technical assistance. Financial support was from the  Fund for Scientific Research Flanders  (HH, SDG and LB),  Universitaire Stichting van België, Interuniversity Attraction Pole network VII-P07 DevRepair (HH) ,  Stichting Diabetes Onderzoek Nederland (HH)  and  Vrije Universiteit Brussel Research Council (HH and MVdC). LB is supported by a  JDRF   Advanced Postdoctoral Grant.
001) (Figure  1B ). Mean tumor weight was significantly decreased in mice that responded to sunitinib treatment compared to controls (P < 0. 001) and in responders compared to mice whose tumors progressed (P < 0. 001); within each group, tumor volume correlated with tumor weight, which was measured after mice were sacrificed (data not shown). In clinical trials, sunitinib efficacy was shown to be independent of the VHL status of the tumors  [12]. Alike, when engrafted 786-0 cells carrying a non functional VHL were treated by vehicle control or sunitinib 60 mg/ kg/ day, median TTP was significantly longer in mice treated with sunitinib compared to placebo (not reached versus 24 days; HR = 33. 64; 95% CI, 4. 94-229. 2; P < 0. 0002) (Figure  S2A ). Median relative tumor volume were significantly decreased in mice that responded to sunitinib treatment compared to controls (P < 0.
Relative to the placebo, statistically significant changes in gene expression (1. 75-fold or greater; p ≤ 0. 05) were observed for 925 genes (245 increased, 680 decreased) in the responders and 181 genes (21 increased, 160 decreased) in the progressive groups (Data File S1). As this is a large number of genes, we sought to identify the key clusters of genes that contribute to the response of RCC tumors to sunitinib. The lists of identified genes whose expression was greater than 1. 75 fold in the responders and progressive groups were input into Metacore, an integrated software suite used for functional analysis of genomic data. Biological process network maps were generated, revealing that sunitinib responsive tumors display statistically significant differential gene expression patterns relative to the placebo reflective of tumor dependent growth and motility i.
To identify the known direct and indirect interactions between the protein products of these genes, we input the lists of Metacore selected genes into the String database, revealing a remarkably strong node in the responders centered on a mass of genes involved in protein translation (Figure  5A ), while interactions in progressive tumors demonstrated nodes involved in vascular regulation and    5B ). These data strongly supported the biological process networks identified by Metacore. While these data indicate the varied responses of RCC tumors to sunitinib treatment, the majority of the gene expression changes in response to the drug were shared between the responding and progressive group. In order to identify the molecular distinction between the two groups, we generated hierarchical clustered heatmaps of the 90 responder and 35 progressive Metacore selected genes (Figure  5C  and 5D) and focused our analysis on the most differentially regulated genes between each treatment.
Sorafenib second line following sunitinib progression 1 Translation_Translation initiation 2 Proteolysis_Ubiquitin-proteasomal proteolysis 3 Transcription_mRNA processing 4 Cell cycle_Mitosis 5 Translation_Elongation-Termination 6 Translation_Elongation-Termination_test 7 Cell cycle_G1-S 8 Cell cycle_G2-M 9 Cytoskeleton_Regulation of cytoskeleton rearrangement 10 Protein folding_Folding in normal condition All 1. 75 fold or greater (P < 0. 05) gene expression changes for first-line sunitinib responders and progressive tumors as well as second-line sorafenib, axitinib, or everolimus were input into Metacore software. The top 10 network process maps were identified using Metacore's proprietary algorithm and ranked according to statistical significance via P values.