dataesr/scientific-paragraphs-categorization huggingface dataset:
1998 Bond et al. , 2000b;; Rocha et al. 2004 ; but see also  Roukema 2000b,a) , but sparked the creation of robust statistical tools, along with greater care in the enumeration of the possible topologies for a given geometry (see, for example, Lachieze-Rey  & Luminet 1995 and Levin 2002 for reviews). With data from the WMAP satellite  (Jarosik et al. 2011) , these theoretical and observational tools were applied to a high-quality dataset for the first time. Luminet et al. (2003)  and  Caillerie et al. (2007)  claimed the low value of the low multipoles (compared to standard ΛCDM cosmology) as evidence for missing large-scale power as predicted in a closed universe with a small fundamental domain (see also  Aurich 1999; Aurich et al. 2004 Aurich et al. , 2005 Aurich et al. , 2006 Aurich et al.
Data description We use Planck maps that have been processed by the various component-separation pipelines described in Planck Collaboration XII (2014). The methods produce largely consistent maps of the sky, with detailed differences in pixel intensity, noise properties, and masks. Here, we consider maps produced by the Commander-Ruler, NILC, SMICA and SEVEM methods. Each provides its own mask and we also consider the conservative common mask. We note that because our methods rely on rather intensive pixel-or harmonic-space calculations, in particular considering a full set of three-dimensional orientations and, for the likelihood methods, manipulation of an anisotropic correlation matrix, computational efficiency requires the use of data degraded from the native HEALPix  (Górski et al. 2005 ) N side = 2048 resolution of the Planck maps.
Because the signatures of either a multiply-connected topology or a Bianchi model are most prominent on large angular scales, this does not result in a significant loss of ability to detect and discriminate amongst the models (see Sect. 5. 3). However, it is worth pointing out that the likelihood and matched circles methods are sensitive to different angular scales as applied to Planck data here. The likelihood method explicitly retains only low-(large-scale) information in its correlation matrix, whereas the matched-circles method considers anisotropies at angular scales down to tens of arcminutes (still large in comparison to the native resolution of the Planck maps). Of course, the matched-circles method exploits the correlation of the small-scale patterns along matched circles potentially separated by large angles; this effect is not generated by intrinsically large angular scale anisotropies but by the boundary conditions of the fundamental domain imposed by the multiply connected topology.
2012 ). These methods have been applied successfully to COBE DMR and WMAP data, and have recently been shown to be feasible for application to Planck data  (Bielewicz et al. 2012). The idea of using the matched circles to study topology is due to  Cornish et al. (1998). In that work, a statistical tool was developed to detect correlated circles in all sky maps of the CMB anisotropy -the circle comparison statistic. In our studies we will use version of this statistic optimised for the small-scale anisotropies as defined by  Cornish et al. (2004) : S + i, j (α, φ * ) = 2 m |m|∆T i,m ∆T * j,m e -imφ * n |n| |∆T i,n | 2 + |∆T j,n | 2 , ( 9 ) where ∆T i,m and ∆T j,m denote the Fourier coefficients of the temperature fluctuations around two circles of angular radius α centered at different points on the sky, i and j, respectively, with relative phase φ *.
76 mask than for the f sky = 0. 78 7-year KQ85 WMAP mask. As a result we obtain weaker -but more conservativeconstraints on topology than for similar analyses of WMAP data  (Bielewicz & Banday 2011). To draw any conclusions from an analysis based on the statistic S ± max (α), it is very important to correctly estimate the threshold for a statistically significant match of circle pairs. We used 300 Monte Carlo simulations of CMB maps, described in detail in Sect. 5. 3. 1, to establish the threshold such that fewer than 1% of simulations would yield a false event.
The likelihood, i. e. , the probability to find a temperature data map d with associated noise matrix N given a certain topological model is then given by P(d|C[Θ C , Θ T , T ], A, ϕ) ∝ 1 √ |AC + N| × exp - 1 2 d * (AC + N) -1 d. ( 11 ) Working with a cut-sky, it is often easier to start the analysis with data and a correlation matrix given in pixel space. However, especially in the realistic case of negligible noise on large scales, the matrix C + N is poorly conditioned in pixel space, and pixel space evaluation of the likelihood is, as a rule, not robust. Indeed, there are typically more pixels than independent modes that carry information about the signal (e. g. , even in the standard isotropic case, sub-arcminute pixels would not be useful due to beam-smoothing; with anisotropic correlations and masked regions of the sky, more complicated linear combinations of pixels even on large scales may have very little signal content).
For full-sky analysis the natural choice of the mode functions is the set of ordinary spherical harmonics Y lm (p) which leads to standard harmonic analysis with modes limited to a suitably chosen max. Here, where we focus on masked data, we have made a somewhat different choice. As a mode set for comparison we use the N m = 837 largest eigenvectors of the C pp matrix, restricted to the masked sky, for the fiducial flat isotropic model with best-fit parameters Θ C. We emphasize that the correlation matrix computed for this reduced dataset has fewer modes, but contains no additional assumptions beyond those of the original C pp. Since computation of C pp matrices for a range of topological models is expensive, we do not aim to determine the full Bayesian evidence P(d|T ) which would require marginalization over all parameters Θ C , Θ T , an overall amplitude of the correlation matrix A (proportional to the physical amplitude σ 8 or the scalar amplitude A s ), and orientation (Euler angles) ϕ, and would in addition be sensitive to the prior probabilities assumed for the size of the fundamental domain.
Therefore, the likelihood is expected to be dependent on the position of the observer. We do not study this dependence here. For each parameter choice, we find the likelihood at the best orientation ϕ of the topology with respect to the sky after marginalizing over the amplitude A of the signal (hence, this can be considered a profile likelihood with respect to the orientation parameters). This likelihood is compared both with the fiducial model applied to the observed temperature map and with the likelihood of the topological model applied to the simulated realization of the isotropic map drawn from the fiducial model. Such a strategy is optimized for the detection of topological signatures. For non-detections, the marginalized likelihood can be a better probe of the overall power of the data to reject a non-trivial topology, and so for real data below, we also show the likelihood marginalized over the orientations ϕ.
Bianchi Masked Planck data are analysed for evidence of a Bianchi VII h component, where the prior parameter ranges adopted are the same as those specified by  McEwen et al. (2013). The analysis is performed on the SMICA component-separated map, using the mask defined for this method, and is repeated on the SEVEM component-separated map for validation purposes (using the mask defined for the SEVEM method). The Bayes factors for the various Bianchi VII h models and the equivalent standard cosmological models are shown in   Notes. For the torus, slab, and chimney, we present limits on the quantity L/2; in curved spaces, limits are on the inscribed-sphere topology scale R i. For the columns labelled "max", we maximize the probability over the orientation of the fundamental domain; for "marg", we marginalize over orientation.
Hence, the results presented here, while corroborating the previous nondetections, use a single, self-consistent, and conservative dataset. The masked sky also increases the possibility of chance patterns in the actual sky mimicking the correlations expected for topologies with a characteristic scale near that of the last scattering surface. Depending on the shape of the fundamental domain, we find R i > ∼ χ rec (Table  2 ) with detailed 99% confidence limits (considering the likelihood marginalized over the orientation of the fundamental domain) varying from 0. 9χ rec for the cubic torus in a flat universe to 1. 03χ rec for the dodecahedron in a positively curved universe, with somewhat weaker constraints for poorly-proportioned spaces that are considerably larger along some directions. In the case of the torus and octahedron topologies, a tighter constraint of 0.
Acknowledgements. The development of Planck has been supported by:  ESA ;  CNES  and  CNRS/INSU-IN2P3-INP (France) ;  ASI ,  CNR , and  INAF (Italy) ;  NASA and DoE (USA) ;  STFC  and  UKSA (UK) ;  CSIC ,  MICINN, JA  and  RES (Spain) ;  Tekes, AoF  and  CSC (Finland) ;  DLR  and  MPG (Germany) ;  CSA (Canada) ;  DTU Space (Denmark) ;  SER/SSO (Switzerland) ;  RCN (Norway) ;  SFI (Ireland) ;  FCT/MCTES (Portugal) ; and  PRACE (EU). A description of the Planck Collaboration and a list of its members, including the technical or scientific activities in which they have been involved, can be found at http://www. sciops. esa. int/index. php?project=planck&page=Planck_Collaboration. The authors thank the anonymous referee for helpful comments and acknowledge the use of the  UCL Legion High Performance Computing Facility (Legion@UCL) , and associated support services, in the completion of this work.
Although DDE transposases are structurally linked, they show an overall low sequence conservation leading to numerous unannotated or misannotated representatives in genome databases. In eukaryotes, comparative analysis of DDE transposases led to the identification of 19 superfamilies  (Jurka et al. 2005). A recent phylogenetic analysis suggested that all eukaryotic cut-and-paste transposable element superfamilies have a common evolutionary origin and define three major phyla  (Yuan and Wessler 2011). Among these groups, the highly mutagenic Mutator and Mutator-like elements (MULEs) represent a diverse family that is related to the prokaryotic IS256 family  (Eisen et al. 1994). In prokaryotes, insertion sequences (ISs) are the simplest and the most abundant autonomous TEs. They were defined as TEs that only code the functions required for their mobility: a transposase gene surrounded by IRs that define the borders of the mobile DNA.
IS have a dedicated repository database, ISfinder (www-is. biotoul. fr, last accessed January 27, 2014), that contains more than 4,000 carefully annotated ISs  (Siguier et al. 2006). Some prokaryotic TEs harbor different "passenger genes," implicated in regulatory or accessory functions such as antibiotic resistance genes which confer a selective advantage to the host. However, the organization of these transposons may be even more complex. We have recently characterized a new family of TEs in streptococci, the TnGBS family, encoding a DDE transposase associated with different conjugative machineries that promote their horizontal transfer  (Brochet et al. 2009; Guerillot et al. 2013). This represents the first family of integrative and conjugative elements (ICEs) in which the phage-like integrase responsible for the excision and integration of the element is substituted by a DDE transposase.
TnGBSs were shown to transpose specifically 15-17 bp upstream different s A promoters  (Brochet et al. 2009). Similarity searches of the public databases revealed IS elements expressing transposases related to TnGBS transposases  (Brochet et al. 2009 ). These enzymes were not related to any known transposase. Here, by a cascade iterated Blast search we have expanded our vision of the diversity of p-MULT with the discovery of four new families, in addition to the IS256 family. TnGBS and related ISs transposases represent one of these new families. Similarity and secondary structure predictions allowed us to determine that these five families share an RNase H fold and to identify, unambiguously, the catalytic triad as well as the IR DNA-binding regions. By systematic analysis of the genomic context we showed that these transposases are responsible for the mobility of ISs both in eubacteria and in archaea but also of ICEs previously described in Mycoplasma (Dordet  Frisoni et al.
Cascade PSI-Blast Search of Transposases Related to Gbs1118 The primary protein sequence of TnGBS2 transposase (Gbs1118) was used as an initial query in a PSI-Blast  (Altschul et al. 1997 ) search against the NCBI nonredundant protein sequence database. Two rounds of PSI-Blast searches were performed without low complexity filter and with otherwise default parameters. Protein hits with an E-value above 0. 005 and query coverage <60% were filtered out. Retained hits were then aligned using the MAFFT algorithm  (Katoh and Standley 2013)  with default parameters and a tree was built with Jalview using the average distances calculated with the BLOSUM62 matrix  (Waterhouse et al. 2009 ). Based on this tree, a protein hit distantly related to the query was chosen to perform a second PSI-Blast search.
Transposase Family Clustering Protein hits retrieved by cascade PSI-Blast were first compared by all-against-all BlastP comparisons. Similarities with an E-value lower than 10 À4 were retained to build a similarity network using the Cytoscape software  (Cline et al. 2007). We applied the force directed layout of Cytoscape to visualize the generated similarity graph where each node corresponds to a transposase homolog interconnected by edges representing the BlastP results. We applied a continuous mapping of the edge opacity to further weigh relationships between transposase homologs (the more opaque edges correspond to lower BlastP E-values). Transposase homologs were then clustered by using the Markov cluster algorithm (MCL) (http://micans. org/mcl/, last accessed January 27, 2014) implemented in the clusterMaker plugin of Cytoscape  (Morris et al.
Identification of Transposable Elements and of Their Insertion Sites The identification of TEs was performed semiautomatically by using scripts written in Python programming language and using the Biopython module (www. biopython. org/, last accessed January 27, 2014). First, the DNA coding sequences of all transposase homologs were retrieved together with 400 bp of up-and downstream sequences. The extracted DNA sequences were then used as BlastN queries against the complete or draft genome sequences in which the TE is inserted. If the BlastN result gave more than three hits, the most likely TE boundaries were determined automatically based on the majority start and end of high-scoring segment pairs (hsp). BlastN results giving multiple hsp that align with the first base of the query likely correspond to larger TEs encoding several open reading frames (ORFs) upstream the transposase gene.
For these transposases, the length of the surrounding DNA sequence was extended until the extremities of the TE were reached. For transposases present in less than three copies, the extracted DNA sequence was compared by BlastN with the genomic sequence of other isolates from the same species, if available. All TE boundaries were manually validated by the identification of IRs and direct repeats (DRs). All transposons and ISs identified in this study (supplementary table  S1 , Supplementary Material online) were submitted to the ISfinder database  (Siguier et al. 2006). Insertion sites and insertion specificity were analyzed upon extracting 300 bp sequences on both sides of the validated TEs after filtering identical insertions. These regions were scanned for putative s A promoters using the PPP software (http://bioinformatics.
Phylogeny and Transposase Sequences Analysis For phylogenetic reconstruction, transposase sequences with BlastP similarity lower than 98% and representative of the diversity of TEs were retained. The transposase sequences were aligned using MAFFT version 6 with the E-INS-I method  (Katoh and Standley 2013)  and manually checked using Jalview  (Waterhouse et al. 2009 ). Aligned positions with more than 60% of gaps were removed before constructing the tree. Phylogenetic relationships were inferred by Maximum likelihood (ML) using MEGA5  (Tamura et al. 2011). Prior to ML analysis, the best protein substitution model of Jones-Taylor-Thornton (JTT) was selected according to the Akaike information criterion given by the ProtTest software  (Darriba et al. 2011). Branch support was determined by 100 bootstrap replications.
Discovery of New Families of Mutator-Related Transposases Transposases from TnGBSs and related ISs show a PFAM rve retroviral integrase domain with a low score  (Brochet et al. 2008). However, we did not retrieve known transposase sequences by BlastP search at NCBI or at the ISfinder Web site. BlastP shows a low sensitivity. To retrieve more distantly related protein sequences, we performed a cascade PSI-Blast search in the nonredundant protein database. After applying the filters described in the Materials and Methods section, we retained 731 protein hits. Interestingly, although 70% of these (517) are currently described as hypothetical proteins, 104 were annotated as Mutator-like transposases, 23 as transposases of the IS256 family, 7 as ISH6 transposases, and 80 as transposases of unknown families.
p-MULTs Are Encoded by Diverse Types of Mobile Elements: ISs, Transposons, and ICEs That Share Transposition Features To systematically identify the TEs that encode transposases of the five p-MULT families, we analyzed the DNA regions on both sides of the transposase genes for IRs and direct repeats (DRs). In total, we accurately identified 424 TEs in addition to the 58 TnGBS related ICE previously described (supplementary table  S1 , Supplementary Material online). The 109 TEs encoding a p-MULT 1 transposase have the genetic organization of IS (fig. 3A ). Based on BLAST analysis performed on the ISfinder database, they all belong to the IS256 family. These ISs are widely distributed among bacterial phyla (Proteobacteria, Firmicutes, Chlamydiae, Actinobacteria, and Deferribactere) and are also present in the archaeal phylum Euryarchaeota.
S1A , Supplementary Material online). Like eukaryotic MULEs, the insertion of these prokaryotic TEs generates DRs of 8 or 9 bp (supplementary table  S1 , Supplementary Material online). We have shown that TnGBSs transpose by production of an extrachromosomal circular form, which acts as a substrate for a plasmid-like replication and conjugative transfer. Similar circular forms of ISLre2 in Lactobacillus reuteri JCM 1112 have been detected by polymerase chain reaction (data not shown). IS256 family ISs also transpose via a circular intermediate  (Loessner et al. 2002)  as do Mycoplasma ICEA and ICEF-I. In these circular forms, the terminal IRs are separated by 6-10 bp sequences derived from one of its two flanking DNA sequences  (Calcutt et al. 2002; Marenda et al. 2006; Brochet et al. 2009; Dordet Frisoni et al.
This replication is dependent on a plasmid-like replicase and promotes the transfer of the ICE  (Guerillot et al. 2013). Mycoplasma ICEs show several features suggesting a transient replication. (Katoh and Standley 2013)  and visualized using Jalview  (Waterhouse, et al. 2009). Only the predicted N2 domain encompassing the minimum IR-binding domain identified in the IS256 transposase  (Hennig and Ziebuhr 2010)  was retained in the alignment. The alignment was filtered for redundancy in order to keep a subset of transposases representative of the diversity of p-MULT 1, 2, 3, and 4 families. Transposases accession numbers are indicated on the left. ICEM (95010) , and ICEM (GM12) , a sequence of 70-286 nt located between the putative tranposase gene and the terminal IR shows more than 83% identity with the DNA region containing the putative single strand origin of replication of the plasmid pMmc-95010  (Thiaucourt et al.
5 ). Shared functional features further underscore the relationships between eukaryotic and prokaryotic Mutator-like transposases. Interestingly, as for IS256, TnGBS, and Mycoplasma ICE, circular forms have been observed in eukaryotic MULE, like Mu1 and Mu1. 7 of the maize  (Sundaresan and Freeling 1987)  and in the a3 MULE of the yeast Kluyveromyces lactis  (Barsoum et al. 2010 ). Thus, this mode of transposition might be a unifying feature of the Mutator superfamily of transposases. The dramatic increase of genomic data provides opportunities to decipher the insertion specificity of transposable elements by comparing multiple insertion sites. We have characterized the diversity of insertion specificity among the five p-MULT families. The insertions of IS256 (p-MULT 1) and of Mycoplasma ICE (p-MULT 5) appeared to be random.
We have previously shown that TnGBS ICEs insert specifically upstream s A promoters in a conserved orientation. We show here that this property is shared by both the ISLre2 family encoding p-MULT 3 transposases and several members of the ISKra4 group (p-MULT 4 family). By comparing transposase sequences from these two lineages, we identified a   6 , the similarity score along the aligned putative transposase sequences was plotted from the MAFFT alignment using the plotcon software of the EMBOSS package. The similarity was calculated by moving a window of 10 aa residues along the aligned sequences and using the BLOSUM62 matrix. Two similarity plots were superimposed. The gray and black curves correspond to the similarity calculated on the alignment of p-MULT 3 plus ISKra4 transposases (p-MULT 4) and of p-MULT 3 plus ISAzba1 and ISMich2 transposases (p-MULT 4), respectively.
Acknowledgments The authors thank  Alexandre Almeida  and  Pierre-Emmanuel Douarre  for critical reading of the manuscript and  Stephane Descorps-Declere  for his help in bioinformatics. They also thank  Carmen Buchrieser ,  Christine Citti ,  Patrick Trieu-Cuot ,  Violette Da Cunha , and  Isabelle Rosinski-Chupin  for fruitful discussions. This work was supported by the  French National Research Agency  (grants  2010-PATH-004-02 ) and the  LabEx  project  IBEID.
Primer 3 Plus software was used for primer design, and the amplification products had sizes between 140 and 160 bp. Primers were designed to have melting points at 60 • C (Table  S1 ) and were commercially synthesized (Biolegio, Netherlands). Amplification reactions were done in triplicate, and analyses were performed using a relative quantification against the reference gene actin (Smp_161930) with the Ct method  (Livak and Schmittgen, 2001).
MORPHOLOGICAL ANALYSES Egg development and worm morphology were monitored by bright-field microscopy (CX21, Olympus; Labovert FS, Leitz), and images were acquired by a digital camera (SC30, Olympus) with CellSens Dimension software (Olympus). For further morphological analyses, adult worms were fixed for at least 24 h in AFA (ethanol 95%, formaldehyde 3%, and glacial acetic acid 2%), stained for 30 min with 2. 5% hydrochloric carmine (CertistainH, Merck), and destained in acidic 70% ethanol. After dehydration in 70, 90, and 100% ethanol for 5 min each, worms were preserved as whole-mounts in Canada balsam (Merck) on glass slides  (Neves et al. , 2005). CLSM images were made on a Leica TSC SP2 microscope using a 488 nm He/Ne laser and a 470 nm long-pass filter in reflection mode as described before  (Beckmann et al.