dataesr/scientific-paragraphs-categorization huggingface dataset:
(i) Security and multi-level access is a key feature in the RDRF The registry framework has two levels of access control, allowing fine-grained control of access: Groups (userlevel) define the permissions granted to each user (functionality); and (ii) Working Groups restrict the content to which Group members have access. In addition, apart from Groups and Working Groups, permissions can also be set on an individual user basis. Working Groups might represent a clinic, hospital, a region or a state. They are private, and data is not shared between working groups. User groups such as treating Clinicians or Geneticists are added to a particular Working Group to allow them to work together. Within the RDRF, the security model consists of several layers: SSL based encryption of all traffic; password access to accounts; and logging of successful and failed user logins.
Conclusions The development of robust sustainable RDR is central to achieving the goals set by the International Rare Diseases Research Consortium (IRDiRC), which aim to have a diagnostic test for most rare diseases and 200 new therapies by 2020. Contemporary thinking is that a disease registry is only as good as the quality of the patient and disease information contained within it. In this paper, we contend that in the longer term, the quality of the system in which the data is contained becomes a significant bottleneck. There are a plethora of registries that differ in naming convention and functionality. Traditionally, not all existing registries are developed with interoperability and security in mind. Currently, there are significant overheads to validate and subsequently synchronise patient data from various regional, state-based, national registries into international resources as successfully demonstrated by the TREAT-NMD network of excellence that allows data collection from more than 40 countries.
albilineans and related species of Xanthomonas. Results: We performed in silico analyses of NRPS genes present in all published genome sequences of Xanthomonas spp. , as well as in unpublished draft genome sequences of Xanthomonas oryzae pv. oryzae strain BAI3 and Xanthomonas spp. strain XaS3. These two latter strains, together with X. albilineans strain GPE PC73 and X. oryzae pv. oryzae strains X8-1A and X11-5A, possess novel NRPS gene clusters and share related NRPS-associated genes such as those required for the biosynthesis of non-proteinogenic amino acids or the secretion of peptides. In silico prediction of peptide structures according to NRPS architecture suggests eight different peptides, each specific to its producing strain. Interestingly, these eight peptides cannot be assigned to any known gene cluster or related to known compounds from natural product databases.
oryzae pv. oryzae strain BAI3 isolated in Burkina Faso  [33]  and the Xanthomonas spp. strain XaS3 isolated in Guadeloupe (French Caribbean island). To date, no genome sequence of an African X. oryzae pv. oryzae strain is available in public databases but a draft sequence of the genome of African strain AXO1947 of X. oryzae pv. oryzae was used recently to identify candidate type III secretion system effector genes  [34]. Xanthomonas spp. strain XaS3 was isolated from the surface of a sugarcane leaf and was characterized initially as a member of the species X. albilineans  [35]. However, recent MLSA (multi locus sequence analyses) analyses showed that this strain, which does not possess the albicidin biosynthesis gene cluster, is close to X. albilineans but belongs to a separate phylogenetic clade (I.
e  [15]. f  [36]. *: XaPPTase gene from strain PXO99A was mis-annotated (correct start codon is upstream of the one deposited in GenBank). **: Consensus signature sequences of PPTase domains as defined by  [14, 15]. PC73 and XaS3, respectively. However, XaPPTase signatures are 100% identical in strains LS155, Xa23R1 and GPE PC73, differing only in one amino acid residue in strain XaS3 (Table  1 ). Genome mining reveals three novel NRPS loci in the genome of X. albilineans strain GPE PC73 In addition to the three NRPS genes characterized previously as being involved in the biosynthesis of albicidin  [21] , the chromosome of strain GPE PC73 possesses seven large multimodular NRPS genes clustered in three loci, hereafter referred to as META-A, META-B and META-C, respectively. These non-characterized NRPS genes share no similarity with NRPS genes from the biosynthesis gene cluster of albicidin.
Phylogenetic analysis of C-domains revealed that the C-domains of the first modules of XALc_1551 and XALc_0772 cluster in a separate clade, distinct from that of the starter C-domains identified by Rausch et al. [6]  in numerous bacteria (Additional file 2). This indicates that these two starter C-domains, which share 81% amino acid similarity, are unusual. The reciprocal best BLAST hit in GenBank for both starter C-domains of META-A and META-C is the N-terminal C-domain of a NRPS gene belonging to the plant-associated bacterium Bradyrhizobium spp. strain BTAi  [37]. The META-B biosynthesis gene cluster of strain GPE PC73 contains four NRPS genes: XALc_1058 (13,686 bp), XALc_1057 (6,378 bp), XALc_1056 (32,124 bp) and XALc_1055 (1,824 bp) (Figure  2 ; Additional file 1). These four genes encode a NRPS system consisting of a total of 16 modules with a continuous C-A-PCP domain arrangement.
Two TE-domains were identified in META-B: (i) a single TE-domain at the C-terminus of the NRPS XALc_1058, and (ii) one double TE-domain on its own encoded by a separate gene (XALc_1055) (Figure  2 ). Like the domain arrangement of META-A and META-C, only essential elongation domains (A, PCP, C and TE) were identified in META-B. Phylogenetic analysis showed that the C-domain of the first module of XALc_1057 belongs to the same clade as starter C-domains identified by Rausch et al. [6] , indicating that it also corresponds to a starter C-domain (Additional file 2). Therefore, the first module of XALc_1057 was assigned as the initiation module of META-B (Figure  2 ). The last module of XALc_1058, which harbors a TE domain, was assigned as the termination module (Figure  2 ). XALc_1055 is the only gene available in GenBank to encode a 'stand-alone' double TE domain, indicating that this gene is not associated to any NRPS system and should be considered as a pseudogene.
strains do not encode identical small molecules. This was concluded from the A-domain specificities of the NRPSs, and the hypothetical peptides are therefore considered strain-specific. Starter C-domains of all four loci META-B share at least 71% amino acid similarity (Additional file 4) suggesting that, although there is currently no experimental evidence, they might be expected to effect N-acylation with a structurally related β-hydroxy-carboxylic acid. Furthermore, the four META-B loci exhibit several C/E dual domains, indicating that they catalyze the assembly of residues with D-configuration. BLAST analyses identified only 188 GenBank entries that exhibit similar dual C/E domains. These 188 entries include nine genes analyzed in the present study (five NRPS genes of strain GPE PC73, two NRPS genes of strain BLS256, and two pseudogenes of strain 306 of X.
axonopodis pv. citri). Draft genome sequence data of strains XaS3 and X11-5A did not indicate the number or distribution of residues in peptides assembled by their respective META-B gene cluster. However, data clearly suggest that these peptides are specific to each strain. In strain X11-5A, the META-B biosynthesis gene cluster is even predicted to control the biosynthesis of two different lipopeptides. A total of five different lipopeptides that do not resemble any compound described to date are predicted for the four Xanthomonas spp. strains due to the presence of the META-B gene cluster. These five lipopeptides could be secreted by the ABC transporter encoded by orthologs of XALc_1064, which are present in all META-B gene clusters. The only common characteristic shared between the loci META-A and META-C of strain GPE PC73 and the locus META-A of strain XaS3, is their unusual starter C-domain, which segregates in a distant phylogenetic clade and shares less that 42% amino acid similarity with starter C-domains of META-B loci or with starter Cdomains identified in numerous bacteria by Rausch et al.
X. sacchari strain NCPPB4393 may also produce new non ribosomal peptide(s). Transporters involved in secretion of these unknown compounds remain to be identified as they are not encoded by the NRPS loci. A total of 14 unknown specificity-conferring signatures of A-domains were found in the four strains GPE PC73, XaS3, X11-5A and BAI3. Only signatures "Unknown2" and "Unknown4" were found in a recently published database that includes 5,118 adenylation domains with unknown signatures  [48]. The other 12 unknown NRPS signatures are not present in this database and could be specific to the genus Xanthomonas. The signature "Unknown1" is predicted to be specific for Dpg because of its presence in all four strains and because of the absence in these strains of any signature similar to those specific to the non-proteinogenic amino acid identified by  [48].
Conclusions This study analyzed published genome sequences of Xanthomonas spp. together with unpublished draft genome sequences of Xanthomonas spp. XaS3 and X. oryzae pv. oryzae strain BAI3 for their genetic capacity to producing small molecules. Table  4  summarizes the in silico data on the non-ribosomally synthesized peptides predicted to be produced by these Xanthomonas strains. Unfortunately, because of the presence of unknown signatures and unusual starter C-domains, we were unable to predict possible structures of any of the products of the identified biosynthesis gene clusters. However, this study revealed that four strains of the genus Xanthomonas possess up to three novel homologous gene clusters, termed META-A, META-B or META-C, encoding NRPS peptides. A phosphopantetheinyl transferase (XaPPTase), which is essential for activation of NRPS enzymes, was identified in all strains investigated.
1. 04) short read assemblers  [52, 53]. In a first step, SOAPdenovo was run with kmer values ranging from 25 to 73 (step of 4) to generate contigs. In a second step, Velvet was run with parameters "-cov_cutoff 5 -min_contig_lgth 100 -max_divergence 0. 05 -exp_cov auto -min_pair_count 10" to generate scaffolds, by using raw reads and SOAPdenovo contigs as input data. The range of kmer values used for Velvet was the same as for SOAPdenovo. The assembly with the maximum N50 value was selected, and remaining gaps were filled with SOAPGapCloser software. The XaS3 draft assembly spans 3,529,206 bp, and consists of 73 contigs of length ranging from 526 to 512,021 bp with a N50 of 168,272 bp. Annotated nucleotide sequences of the regions identified in these 73 contigs as containing A-domains and/or NRPS associated genes are provided in Additional file 7.
Determination of the complete sequence of the 82-kb length region containing META-B in X. oryzae pv. oryzae strain BAI3 On the basis of the draft genome sequence of strain BAI3, three scaffold DNA sequences were identified as belonging to META-B. The sizes of these DNA regions are 35,406 bp, 16,409 bp and 22,029 bp, respectively. Seventeen clones from a 10-kb shotgun library of strain BAI3 were identified by BLAST analyses to contain fragments of the META-B NRPS cluster. These clones are ABP0AAB3YI02, ABP0AAB3YP05, ABP0AAB8YK02, ABP0AAB8YE14, ABP0AAB5YJ09, ABP0AAB4YK08, ABP0AAB3YL17, ABP0AAB6YE03, ABP0AAB6YC14, ABP0AAB5YG12, ABP0AAB7YB12, ABP0AAB5YK06, ABP0AAB5YJ04, ABP0AAB7YD04, ABP0AAB3YG10, ABP0AAB5YE07 and ABP0AAB3YM11. Sequences of the insert ends were mapped onto the three scaffold DNA sequences.
0 kb and to sequence clones ABP0AAB3YG10, ABP0AAB3YM11, ABP0AAB5YE07, ABP0AAB5YJ04, ABP0AAB6YC14, ABP0AAB6YE03, ABP0AAB7YB12 and ABP0AAB7YD04 (Additional file 8). DNA sequencing was performed by Beckman Coulter Genomics (Takely, UK). Sequence reads were used to assemble the complete 81,740-bp META-B region of strain BAI3 (Genbank accession n°JQ348075). In silico analyses of NRPS Specificity of adenylation domains in NRPS and signatures were predicted using software available at http://nrps. informatik. uni-tuebingen. de/Controller?cmd=SubmitJob [54]. In silico analyses were performed on NRPS genes present in the finished annotated genome sequence of X. albilineans strain GPE PC73 (GenBank accession n°: NC_013722. 1), in the non-annotated draft genome sequence of X. oryzae pv. oryzae strain X11-5A (GenBank accession n°: AFHK00000000.
1; sequences analyzed in the current study are annotated in Additional file 9), in the unpublished annotated sequence of the 82-kb length region containing META-B in X. oryzae pv. oryzae strain BAI-3 (Genbank accession n°JQ348075), in the unpublished sequence of the contigs of strain Xanthomonas spp. XaS3 (sequences analyzed in the current study were annotated in Additional file 7), in the finished annotated genome sequence of X. oryzae pv. oryzicola strain BLS256 (nucleotide GenBank accession n°: CP003057. 1), in the finished annotated genome sequence of X. axonopodis pv. citri strain 306 (nucleotide GenBank accession n°: AE008923. 1), and in the non-annotated draft genome sequence of X. sacchari strain NCPPB4393 (nucleotide GenBank accession n°: AGDB00000000. 1).
Phylogenetic analysis The phylogenetic tree presented in Additional file 2 was reconstructed using the maximum likelihood method implemented in the PhyML program. The LG substitution model was selected, assuming an estimated proportion of invariant sites (of 0. 01) and four gamma-distributed rate categories to account for rate heterogeneity across sites. The locus analyzed was the C-domain. Multiple alignments of the amino acid sequences of the C-domain and for all taxa were performed using ClustalW. The phylogenetic tree was calculated with PhyML; http://atgc. lirmm. fr/phyml/, version 2. 4. 4. Five hundred bootstrap replicates were performed with PhyML program. Data are available from the Dryad Digital Repository: http://doi. org/10. 5061/ dryad. gh7h8.
Acknowledgements We thank  Claude Bragard  for access to sequence data of X. translucens. We thank  Helen Rothnie  for English editing. CG was supported by a post-doctoral fellowship awarded by the  Agence Nationale de la Recherche ,  France  ( ANR-09-BLAN-0413-01 ). MM was supported by a PhD Fellowship awarded by the  Région Languedoc-Roussillon  and by the  Centre de Coopération Internationale en Recherche Agronomique pour le Développement, France. GPR was supported by a PhD fellowship awarded by the  Région Languedoc-Roussillon  and by the  Centre National de la Recherche Scientifique, France  (grant  07-845 ). PR was supported by a  Marie Curie Outgoing International Fellowship  from the  European Commission. The project was supported by a joint research grant of the  Agence Nationale de la Recherche  to  MR  ( ANR-09-BLAN-0413-01 ) and the  Deutsche Forschungsgemeinschaft  to  RDS  ( DFG SU239/11-1 ).
). The reciprocal best BLAST hit in GenBank for the XaPPTase gene of X. albilineans is the XaPPTase gene from X. oryzae. This X. axonopodis pv. citri strain 306 vipA XAC2105 Leu phage related sequences XAC2098 NRPS XAC2097 NRPS Gly Cys Gly XAC2093 pgsA X. oryzae pv. oryzicola strain BLS256 vipA XOC_2570 Leu XaPPTase XOC_2573 NRPS XOC_2574 NRPS XOC_2575 phage related sequences Gly Cys Gly pgsA XOC_2583 8 genes Gly Cys Gly XOC_2983 to XOC_2975 X. oryzae pv. oryzae African strain BAI3 vipA Leu XaPPTase phage related sequences phage related sequences pgsA 8 genes X. oryzae pv. oryzae PXO99A and KACC10331 Asian strains MAFF 311018, vipA XOO3082 XOO_2936 PXO_01511 Leu XaPPTase XOO3083 PXO_01508 XOO_2935 phage related sequences phage related sequences XOO2290 XOO_2168 PXO_01580 Gly Hp Cys Gly PXO_01581 XOO2291 XOO_2169 pgsA XOO3279 to XOO3269 PXO_01241 to PX0_01248 XOO_3104 to XOO_3097 8 genes X.
The twelve phR T spectra were imported into the MALDI BioTyper software (version 2. 0, Bruker) and analyzed by standard pattern matching (with default parameter settings) against the main spectra of 3,769 bacteria, including spectra from nine validly published Brevibacillus species that were used as reference data in the BioTyper database (updated March 15 th , 2012). The method of identification includes the m/z from 3,000 to 15,000 Da. For every spectrum, 100 peaks at most were taken into account and compared with the spectra in the database. A score enabled the presumptive identification and discrimination of the tested species from those in a database: a score > 2 with a validated species enabled the identification at the species level; a score > 1. 7 but < 2 enabled the identification at the genus level; and a score < 1.
Genome project history The organism was selected for sequencing on the basis of its phylogenetic position and 16S rRNA similarity to other members of the Brevibacillus genus, and is part of a study of the human digestive flora aiming at isolating all bacterial species within human feces. It was the fifth genome of a Brevibacillus species and the first genome of Brevibacillus massiliensis sp. nov. The Genbank accession number is CAGW00000000 and consists of 132 contigs. Table  3  shows the project information and its association with MIGS version 2. 0 compliance  [42].
Genome annotation Open Reading Frames (ORFs) were predicted using Prodigal  [43]  with default parameters but the predicted ORFs were excluded if they spanned a sequencing gap region. The predicted bacterial protein sequences were searched against the GenBank database [44] and the Clusters of Orthologous Groups (COG) databases using BLASTP. The tRNAScanSE tool  [45]  was used to find tRNA genes, whereas ribosomal RNAs were found by using RNAmmer  [46]  and BLASTN against the GenBank database. Lipoprotein signal peptides and numbers of transmembrane helices were predicted using SignalP  [47]  and TMHMM  [48] , respectively. ORFans were identified if their BLASTP E-value was lower than 1e-03 for alignment length greater than 80 amino acids. If alignment lengths were smaller than 80 amino acids, we used an Evalue of 1e-05.
Such parameter thresholds have already been used in previous works to define ORFans. To estimate the mean level of nucleotide sequence similarity at the genome level between B. massiliensis strain phR T , B. laterosporus strain LMG15441 (GenBank accession number AFRV00000000) and B. brevis strain NBRC100599 (GenBank accession number AP008955) and B. agri strain BAB-2500, we compared genomes two by two and determined the mean percentage of nucleotide sequence identity among orthologous ORFs using BLASTn. Orthologous genes were detected using the Proteinortho software  [49].
Asaccharolytic. Cells are susceptible to penicillin G, amoxicillin, amoxicillin + clavulanic acid, ceftriaxone, imipenem, erythromycin, doxycycline, rifampicin, vancomycin, ciprofloxacin, gentamicin, nitrofurantoin and resistant to metronidazole and trimethoprim/sulfamethoxazole. The G+C content of the genome is 53. 1%. The 16S rRNA and genome sequences are deposited in Genbank and EMBL under accession numbers JN837488 and CAGW00000000, respectively. The type strain phR T (= CSUR P177 = DSM 25447) was isolated from the fecal flora of an obese patient in Marseille, France.
The aggregate p-value for this data set as determined by Monte-Carlo simulation was 3 × 10 -9 , indicating that our results were highly unlikely to be accounted for by chance. The increased proportion of biased embryos observed after 4-cell 4-OHT treatment, as opposed to the 8-cell 4-OHT treatment, is most likely a result of our enhanced ability to detect bias in the 4-cell treated data set. The earlier 4-OHT treatment produced larger clones, resulting in greater statistical power. Importantly, embryos with detectable bias were comparable to unbiased embryos with regard to total number of cells (biased: 73±15, unbiased: 72±28), and the percentage of total cells that contributed to the ICM (biased:12%±4%, unbiased: 16%±3%). As we observed a large number of colors that occurred with approximately equal frequency (Tables  S3  and 4 , Figure  S1 ) it is likely that most recombination events that we analyzed were unique.
For cell membrane staining, zona-denuded blastocysts were incubated overnight in Vybrant DiO cell labeling solution (Invitrogen), diluted 1:100 in KSOM at 37°C, 5% CO 2. For postimplantation analysis, E3. 5 blastocysts were transferred into uteri of pseudopregnant females 2. 5 dpc. Embryos were dissected from the uterus at E7. 5, fixed in 4% paraformaldehyde, and imaged. For recombination at E13. 5, 2. 5 mg Tamoxifen was administered orally to Rainbow3 females previously mated to CAGG-CreER males. Embryos were recovered 2 days later, cryosectioned and imaged. Most image analysis was performed using the Imaris 6. 0 image processing software (Bitplane). Nuclei were detected by far-red staining, and independently assigned a color and a position within the blastocyst. Image J was used for quantification of relative fluorescence intensities.
Acknowledgments We thank  Harvard GMF  and  A. McMahon  for providing transgenic animals and  D. Smith ,  S. Turney ,  G. Birkhoff ,  S. Rompani , and  S. Fouquet  for technical assistance. This work was supported by  NICHD  grant # HD045732-03 , and  NIGMS P01  grant  GM099117  to K. E. , and  HHMI.
Materials and methods Using information from the population-based Geneva Cancer Registry, we identified 71 men (0. 7%) out of 10,800 primary invasive breast cancers between 1970 and 2009. The Geneva Cancer Registry collects information from various sources and is considered to be accurate  [12]. All hospitals, pathology laboratories and private practitioners in the canton are requested to report all cancer cases to the Registry. Trained tumour registrars systematically abstract data from medical and laboratory records. Physicians regularly receive enquiry forms in order to complete missing clinical and therapeutic data. Recorded data include sociodemographic information, tumour characteristics (coded according to the International Classification of Diseases for Oncology, ICD-O), treatment given during the first six months after diagnosis, occurrence of other primary cancers, and survival status  [13].
Acknowledgement:We thank  Milena Uehlinger  for her technical and editorial assistance Funding / potential competing interests: This study was financially supported by grants  KLS 02544-02-2010  and  KLS 2946-02-2012  from the  Swiss Cancer League. The authors have no conflicts of interest and do not have any disclosures to make. Correspondence:  Professor Simone Benhamou, PhD ,  Geneva Cancer Registry ,  55  Bd. de la Cluse, CH-1205 Geneva, Switzerland, simone. benhamou[at]inserm. fr.
We assessed the consequences of deletion of the SCH9 gene from a haploid derivative of EC1118, 59A (strain sch9::KanMX 59A). We examined the response of the SCH9-deleted strain to nutritional imbalances and its effect on cell viability. In SM71 LF5% the production rate of CO 2 by the SCH9-deleted strain was similar to that of the non-deleted controls (data not shown), and viability was similar. However, in SM142 LF5% the viability of the SCH9-deleted strain was significantly greater than that of the wild-type strain, reaching 80% versus 60% in the wild type strain at 60 g of CO 2 produced (Figure  6 ). Thus, deletion of SCH9, like inhibition of TOR by rapamycin, favoured survival in conditions of lipid/nitrogen imbalance. This suggests that cell death in such nutritional conditions is controlled by Sch9p and TOR activity.