dataesr/scientific-paragraphs-categorization huggingface dataset:
Functional annotation of Cfp1 target genes We have observed that Cfp1 substantially affects the H3K4me3 levels at a large number of promoters and we next asked whether it specifically targets genes which share particular functional pathways. We performed an enrichment analysis for gene ontology (GO) terms using the Ontologizer package  [36]. As a study set we used a set of 759 genes associated with differential promoters detected by MMDiff in both experiments (AB. 1 and AB. 2) and which showed a decrease in H3K4me3 upon depletion of Cfp1-/-and similarly for DESeq (322 genes). These two sets were contrasted with a population set consisting of 11,459 genes that showed substantial enrichment for H3K4me3 in WT and Resc in both experiments. Interestingly, despite the small overlap between the MMDiff set and the DESeq set (only 18% of the combined set are shared), 9 out of the 10 most enriched GO terms are consistent between the two sets: These GO terms include 'RNA processing', 'RNA binding', 'ribonucleoprotein complex biogenesis', 'structural constituents of ribosomes' and 'ribonucleoprotein complex', which were all highly enriched in the downregulated DMP sets (adjusted p-values < 10 -6 ).
We observed a minimum of BIC at k = 18 clusters, which proved to be robust against different initialisations of the algorithm, and the same minimum was found both in the WT and Resc data sets. Figure  6A  presents a heat map visualisation of the clustering results. Average H3K4me3 and Pol II profiles for three clusters are shown in Figure  6B  and C. Remarkably, genes within the same H3K4me3 cluster also appear to have distinctive Pol II profiles and wider H3K4me3 peaks are reflected in broader binding of Pol II. We further investigated the relationship between differential histone modification and shape clustering by analysing how the detected DMPs are distributed over the clusters, see Table  2. We find that clusters 12, 14-16, and 18 are highly significantly (p<0. 001) enriched for DMPs.
Application 2: H3K27ac To further explore the broader applicability of MMDiff, we applied it to a H3K27ac ENCODE data set. This epigenomic mark is known to localize around enhancer elements and distinguishes active enhancers from poised ones  [42]. Here we compare two human cell lines, K562, an immortalised myelogenous leukemia line, and GM12878, a lymphoblastoid cell line. We use two replicates per cell line and analyzed 69,577 regions  derived from the respective ENCODE broadPeak files  [43]  after merging overlapping peaks  [7]. Using DESeq, 25% (18,080) of all peaks appear to be differential between the two cell lines. With MMDiff we only detect 5631 changes, of which 1827 are unique to MMDiff. Figure  7A  shows a typical example region which was detected by DESeq but not MMDiff. It is apparent that, despite a large fold change, the shapes of the peaks are very similar in the two cell lines.
Application 3: CTCF binding Finally, we tested MMDiff on a ChIP-Seq data set measuring the genome-wide binding of the transcription factor CTCF. CTCF is a transcriptional repressor which also plays a fundamental role in regulating the 3-D structure of chromatin  [44]. As such, it has been widely studied in recent years, with several ChIP-Seq experiments identifying thousands of binding sites across the genome. Here we used an ENCODE CTCF ChIP-Seq data set consisting of two replicates from three mouse tissues; cortex, cerebellum and liver  [28]. The choice of tissues was deliberately heterogeneous to check the ability of MMDiff to identify both subtle changes (as expected between cortex and cerebellum) and more marked changes between brain tissues and liver. We used the provided broadPeaks files and after merging overlapping peaks we obtained 49,762 sites for further analysis.
Conclusions ChIP-Seq is one of the most widely employed experimental techniques in functional genomic and epigenomic studies, yet statistical analysis of ChIP-Seq data still poses many challenges. In this paper, we address the problem of statistical testing in ChIP-Seq data sets, and propose a non-parametric methodology which is capable of accounting for the highly structured nature of this type of data. Compared with techniques based on total counts, MMDiff can identify localised changes which alter the shape of a peak. The identification of such changes is particularly relevant in the light of recent findings that suggest a functional significance of the shape of histone modifications. For example, an analysis of H3K27me3 patterns around CTCF peaks, carried out as part of the ENCODE project, reported that the observed asymmetric shapes of H3K27me3 support the role of CTCF sites in delimiting active and polycomb-silenced domains  [1].
An approach which is related to ours has been recently proposed for the purpose of alternative isoform detection from RNA-Seq data  [23]. While the methodology proposed in that paper also relies on MMD, the application domain is significantly different, as is the treatment of biological noise. In the context of ChIP-Seq data, our empirical results, both on simulations and on three independent data sets, demonstrate that our approach is complementary to count-based methods such as DESeq. A practically advisable strategy may be to couple the two methods within an analysis pipeline, allowing analysts to detect both peaks that change in shape and peaks that only exhibit changes in total counts of reads, while maintaining the overall shape of the peak. As for all statistical testing methods, it is worthwhile to emphasize that multiple biological replicates are necessary to get a reliable estimate of the biological variance.
Data from different biological conditions were compared in an "everyone against everyone" scheme, and log 2 quotients ("log Q") were then determined as the mean of the weighted individual log Q values  [15]. For these inter-assay comparisons, the NeONORM method was used  [18]. pvalues were determined using a t-test and a pFDR correction. Multiple probes for a single gene and cross-reactivity of a single probe to several genes, as well as the resolution of probe-ID annotations, was accomplished according to the standards defined previously  [19]. Heat-maps were created according to standard methods. To underline the single-color chemiluminescence detection character of the AB1700 system, we used a blank (signal ¼ 0) to bright green (signal >10) gradient to represent the signal intensities. Combining GO, Kegg and PANTHER annotations, we assigned all the probes on the microarrays to pathways or biological processes.
TaqMan low density array (TLDA) Total RNA was isolated using the Nucleospin RNAII system (MachereyeNagel) as described. The synthesis of cDNA was performed with 100 ng of RNA for each sample using a High-capacity cDNA Archive kit (Applied Biosystems, Foster City, CA). Gene expression was analyzed using a custom designed TLDA in a 7900 Real-Time PCR System (Applied Biosystem) following the conditions stated by the manufacturer. Analysis was carried out using the Real-Time StatMiner software from Integromics (Philadelphia, USA). Relative mRNA levels (2 ÀDDCt ) were determined as previously described  [15]  by comparing: (i) the PCR cycle thresholds (Ct) for the gene of interest and the Cts of 5 normalizing genes (Actb, 18S, Dpp, Polr2j, Ube3b) to calculate the DCt; and (ii) the DCt values for treated and control groups (DDCt).
When bacterial lung colonization was analyzed in mice infected with a high dose of B. pertussis, we observed differences in the bacterial infection kinetics. It is important to note that both C3H/HeN and C3H/HeJ mice were equally infected because similar numbers of bacteria were detected in lungs 2 h post-infection. In agreement with previous studies  [20] , at 24 h post-infection, differences in bacterial load were detected in both mouse strains. We observed that 1. 0 AE 0. 1 Â 10 7 CFUs were recovered from the lungs of C3H/ HeJ infected mice, and 6. 8 AE 0. 2 Â 10 6 CFUs were recovered from C3H/HeN infected mice ( p 0. 01). These differences were sustained at 48 h post-infection (8. 9 AE 0. 2 Â 10 6 CFUs C3H/HeJ and 1. 6 AE 0. 2 Â 10 6 CFUs C3H/HeN; p 0. 01) and later time points (data not shown), following a kinetics comparable with previous reports  [9, 20].
Acknowledgments This work was supported by the  EU STREP INCO  grant SavinMucoPath n  032296  to DH, JCS and MR and grants from  ANPCyT  and  CICBA grant  to DH and MR. DH is a member of the Scientific Career of CICBA. MR and GM are members of the Scientific Career of CONICET. AE have a fellowship from  CONICET. Work in AB's lab has received funding from the  Genopole Evry  for this study and funding from the  Agence Nationale pour la Recherche  ( ANR, Physio2007 ) for the development of novel data-analysis methodology.
Observations and data analysis The OHP images were reduced with the Image Reduction and Analysis Facility (IRAF 6 ). The images were bias-substracted and flat-fielded using the imcombine and imarith routines. A first astrometric reduction used the ccxymath routine because the header of the fits files does not contain the required WCS 7 keywords. Photometric reduction used customized software (for details about the protocol see  Taris et al. 2011)  after the detection of the stars by Sextractor software 8   (Bertin & Arnouts 1996). The magnitude of these stars were compared to the known magnitudes of the stars in the GSC2. 3 catalog  (Lasker et al. 2008). After a 3σ rejection of the outliers, the formal uncertainty of the photometric calibration is roughly 0. 2 mag in both R and V. The photometric reduction of the TAROT and Zadko telescopes is described by  Damerdji et al.
(2007). It is based on a measurement flux by the Sextractor software. The precision of the photometry is 0. 05 mag relative to the same reference star chosen close to the target. The accuracy is only 0. 4 mag, since it is limited by the photometric calibration of the USNO A2 catalog. However, because this study is concerned with photometric time variation, we retain the value of 0. 05 mag as the uncertainty of a series of measures obtained by a given telescope.
QSO B0954+658 The host galaxy of this BL Lac is marginally resolved (the source is definitely resolved, but the data are insufficient for determining a firm Hubble class) on the Gunn r band images of the CFHT  (Wurtz et al. 1996). QSO B0954+658 is a well studied BL Lac object in the optical band. Raiteri et al. (1999)  gives light curves in the B and V bands on long timescales (several years) together with radio curves.
ICRF J133245. 2+472222 Nineteen papers relating to this QSO are found in SIMBAD, but none of them refers to magnitude variation or morphology in the optical domain. ICRF J135256. 5-441240 Confusing data have been published about the optical identification of the BL Lac ICRF J135256. 5-441240 and the Seyfert I galaxy QSO  B1349-439 (Veron 1996. This BL Lac was observed by  Heidt et al. (2004)  with the ESO-VLT on Cerro Paranal, Chile. They could not resolve the target in the I band. No information was found for the magnitude variation in the optical domain.
All observations presented in the frame of this work were made before 6 January 2012. They are presented in Table  4  and will be part of the data provided to users through a database. This database is currently under construction in the framework of the ICRS-PC and will be the subject of a forthcoming paper. It is a fact that the variation in the AGN's radiostructure degrades the positional accuracy of the radiocenter's position. Instabilities/variability in AGN components may degrade the photocenter accuracy. For example, it is well known that changes in the radio structure, such as those detected in VLBI, may degrade the radiocenters position. Also in the optical domain, instabilities in the accretion disk may contribute to a change in the optical photocenter  (Popovic et al. 2012). We note that the photocenter changes due to variability in regions as small as 1 pc (that include accretion disk and broad emission line regions) in objects towards z ∼ 0.
The quasars observed at the OHP can be divided into (i) 16 objects appearing in the SDSS and there classified both as quasars and point sources and (ii) 49 objects that do not belong in the SDSS as quasars (some might appear under other classifications). All targets common to the SDSS are found here as not distinguished from the PSF given by local stars. Among the non-SDSS objects, there are 11 Seyfert1, 23 BL Lac, and 15 QSO objects as classified from the CDS database. From there the images can be examined (mostly taken from the DSS) and for none of them the host galaxy has been seen. Nonetheless, among those objects (like for example B0007+106 or B0954+658, respectively classified as Seyfert1 and BL Lac), host galaxy had been previously resolved in more favourable conditions of SNR and pixelization.
Unknown means that no information was found in the SIMBAD database whether for morphology or for variability. an angular value close to the astrometric uncertainty of the final Gaia catalog. Among the 70 initial targets, roughly 50% have an unknown or not well-established morphology. Seventeen targets have high-resolution images coming from the Hubble Space Telescope and are currently under investigation in the search for the host galaxy. Twenty-two other targets have no information and will be the subject of dedicated high-resolution observations to find their morphology. In the third part of this paper we showed that the morphological indexes of the targets do not vary above the noise, as obtained from the images coming from these four telescopes and detectors. The results we obtained are in good agreement with other studies based on DSS or SDSS images.
We showed that the quasars are a special group of objects compared to the stars used for comparing the PSF parameters. The detailed results for these morphological indexes, their numerical values, the stability of the time series of the indexes, and the comparison with the morphological analysis currently in progress with the GALFIT and IRAF software will be presented as second part of the present work. The results in this paper are being pursued to monitor the target's magnitude as given in the first list of Bourda. Another list of targets has been established to achieve the link between the radio and the optical reference frame  (Bourda et al. 2010). We then plan to observe this second set of targets coming from the NVSS (NRAO VLA Sky Survey) catalog but with other robotic telescopes because all these targets are spread over the northern hemisphere.
The same kind of result are expected in terms of variability and morphology and will be published as third and fourth parts of the present work. Our group is also involved in other works to study the morphology of AGN in the area of a Gaia Workpackage (GWP-S-335-13000) together with the relationship between the radio and optical observations. For this last topic, dedicated observations are planned in these two wavelength domains. Furthermore, a database dedicated to AGN optical images is currently under construction in the framework of the Virtual Observatory and will be presented in a forthcoming paper. Notes. The number of observation in September 2011 is given for each telescope (ESO or OCA for the Tarots, OHP for the T120, and Zadko for the Zadko telescope) used in this work plus images obtained from the HST archive to search for the host galaxy.
Acknowledgements. We are very grateful to an anonymous referee for very useful comments and to  R. Giraud  from the  "Observatoire de Haute Provence"  for his help in the observation of our targets with the T120 telescope. The authors are also grateful to  J. Adams  for careful language editing of the manuscript. The  French AS-Gaia  is kindly acknowledged for the financial support of the observation campaign at the  Observatoire de Haute Provence. A. H. A. acknowledges  CNPq  grant  PQ306775/2009-3  and  PARSEC International Incoming Fellowship of the Marie Curie 7th ECP.
Scanning and data analysis: The BCA-oligo array was scanned at a 3 micron resolution on the high-resolution Agilent scanner. The scanner measures the fluorescence intensity of two dyes simultaneously (wavelengths of 532 and 635 nm) from labeled samples of nucleic acid bound to the BCA-1 test. The scanned images were analyzed using Feature Extraction software, and the graphic display of the data was generated by Cytogenomics software (Agilent Technologies). Each oligo was positioned in the human genome in accordance with NCBI Build 37 (UCSC hg19, February 2009). Cytogenomics software uses the Agilent ADM-2 algorithm. For these analyses, a probe was deemed to be deleted if its standardized log2 ratio was \-0. 2 and was duplicated if its standardized log2 ratio was greater than 0. 2. The software segments displayed the data by grouping together those probes which have a proximate position in the genome and ratio averages which correspond to loss or gain (Fig.
A synoptic table of chromosomal arms by aberrations is given in Fig. 2 , according to the 2004 WHO aggressiveness classification of non-muscle-invasive B-TCC. We looked for Pearson correlation between chromosomal aberrations given in Fig. 2. Finally, BCA-1 positivity ([9 %) was calculated for presence and absence of high-grade tumor on the biopsy. The distributions were compared by logistic regression. Odds ratios (ORs) as a measure of relative risk of high-grade disease and their 95 % confidence intervals (CIs) were estimated. Software MedCalc12. 7. 0 (Acacialaan 22, B-8400 Ostend, Belgium) was used for statistical analysis.
This approach allows flexibility to discuss unexpected and relevant topics  (Bryman, 2004). It allows the researcher to develop a holistic overview of the context under study by capturing indepth data based on consumer perceptions  (Miles and Huberman, 1994; Saunders et al. , 2003). The principal researcher conducted the interviews during Autumn 2009, Winter 2010 and Summer 2012. Interviews were conducted at a pre-arranged location either at the respondents' home or work place. For purposes of analysis, we voice recorded the interviews on a portable device with the respondents' consent. We briefed all interviewees on the nature of the study and aims of the research prior to the interview. We then encouraged the interviewees to describe their perceptions and experiences as consumers  (Churchill, 1995).
However, BLASTp revealed a maximum identity of about 30% between ORF2 and Rep proteins of circoviruses and cycloviruses, with a coverage of ~85% (aa 5 to 80, Viral_Rep superfamily [pfam02407], and aa 150 to 212, P-loop_NTPase [pfam00910]). The other ORFs did not have any viral identity using BLASTp. The lack of sequence identity and the differences in genome organization and size indicated a new virus family or genus. To our knowledge, this is the first circular single-stranded DNA virus in insects that is not related to cycloviruses  (7, 8) , circoviruses  (9) (10) (11) , nanoviruses  (12, 13) , or geminiviruses  (14, 15) , and it may be of interest in elucidating the evolution of this rapidly expanding virus group. Nucleotide sequence accession number. The GenBank accession number for AdVVV is KC543331.
RNA extraction, reverse-transcription and quantitative-PCR Total RNA was extracted from mouse adipose tissue or from human primary cultures using the RNeasy total RNA minikit (Qiagen). Reverse transcription and semi-quantitative real-time PCR amplification on the ABI 7300 apparatus (Applied Biosystems, Life Technology, Courtaboeuf, France) were performed as previously described  [25]. Specific primers (Proligo, Sigma-Aldrich, Lyon, France) used for amplification of target genes were designed using the Primer3 Input program and were the following: Forward 59CTGCATTGAACAGACCACAGA39 and reverse 59TCTTGAACTGCAGGTGGATG39 primers for human NOV and forward 59CTGCATTGAACAGACCACAGA39 and reverse 59TCTTGAACTGCAGGTGGATG39 for mouse NOV. The comparative Ct method  [26]  was used to calculate gene expression values.
NOV is expressed in human adipose tissue Using immunohistochemistry, we found that NOV protein was present in both subcutaneous and omental adipose tissue from obese patients (Figure  2B ). On serial sections stained for NOV, using CD68 (a specific macrophage marker) and perilipin (a specific adipocyte lipid droplet marker), we determined that NOV was not only expressed in adipocytes but also in macrophages, especially those in crown-like structures surrounding the adipocytes. However, not all adipocytes and macrophages were positive for NOV. No staining was observed when using IgG depleted from NOV-specific IgG (flow through, FT) (data not shown). NOV expression was also assessed in primary cultures of human macrophages and adipocytes. As shown in Figure  2C -D NOV expression at mRNA and secreted protein levels could be easily detected in both types of cultures.
Acknowledgments We would like to thank  Sylvie Dumont  from the  Service of Anatomopathology  and  Pierre-Olivier Marchal  from  UMR_S938, Saint-Antoine Hospital , for their technical support. The authors thank  Marie-Christine Federspiel ,  Corinne Cherfils  and  Valerie Fesel-Fouquier  from the  Department of Metabolic Biochemistry  for expert technical assistance and  Mme Christine Baudouin ,  Dr Florence Marchelli , and  Mme Patricia Ancel  ( Center of Research on Human Nutrition, Pitie-Salpetriere Hospital, Paris, France ) who were involved in patients' recruitment, data collection and sampling at the  Center of Research on Human Nutrition ,  Paris Pitie-.
This work was supported by the  Institut National de la Santeet de la Recherche Medicale (INSERM) , and by grants from the  Institut National du Cancer (INCA)  and the  Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC). JP was a recipient of financial support from the  ANRT  ( Association National Recherche et Technologie ),  CIFRE. The authors acknowledge support from the  Assistance Publique-Hopitaux de Paris (APHP)  and the  Direction of Clinical Research (CRC) , which promoted and supported our clinical investigation ( CRC NCT 0047658 ) and  PHRC 0702. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Since the annihilation amplitudes are expected to be small in the SM and are often accompanied by other topologies, they are difficult to determine unambiguously. These can however be measured cleanly in B + c → K 0 S K + decays, where other amplitudes do not contribute. Standard Model predictions for the branching fractions of pure annihilation B + c decays range from 10 -8 to 10 -6 depending on the theoretical approach employed  [13]. In this Letter, a measurement of the ratio of branching fractions of B + → K 0 S K + and B + → K 0 S π + decays with the LHCb detector is reported along with a determination of their CP asymmetries. The data sample corresponds to integrated luminosities of 1 and 2 fb -1 , recorded during 2011 and 2012 at centre-of-mass energies of 7 and 8 TeV, respectively.
Detector, data sample and event selection The LHCb detector  [14]  is a single-arm forward spectrometer covering the pseudorapidity range 2 < η < 5, designed for the study of particles containing b or c quarks. The detector includes a high-precision tracking system consisting of a silicon-strip vertex detector (VELO) surrounding the pp interaction region, a large-area silicon-strip detector located upstream of a dipole magnet with a bending power of about 4 Tm, and three stations of silicon-strip detectors and straw drift tubes placed downstream. The magnetic field polarity is regularly flipped to reduce the effect of detection asymmetries. The pp collision data recorded with each of the two magnetic field polarities correspond to approximately half of the data sample. The combined tracking system provides a momentum measurement with relative uncertainty that varies from 0.