dataesr/scientific-paragraphs-categorization huggingface dataset:
ACKNoWLeDGMeNTS We thank  H. Lin ,  F. Zhao ,  J. Lei ,  Z. Zhu  and  Q. Wang  for their support of the tongue sole genome project. We thank  Z. Liu ,  Z. Zhuang ,  R. Li ,  Z. Jiang ,  P. Ni ,  X. Qian  and  T. Xu  for discussion. We thank  J. Zhai ,  S. Liu  and  Z. Li  for their help in the culture of tongue sole families. We thank  M. Yi  and  L. Huang  for their help with chromosome FISH. We are grateful to the faculty and staff of Yellow  Sea Fisheries Research Institute ,  CAFS  and  BGI-Shenzhen , whose names were not included in the author list but who nevertheless contributed to this project. This work was supported by grants from the  Special Fund for Agro-Scientific Research  in the Public Interest (200903046) of China to S. C. , the  State 863 High Technology R&D Project of China  ( 2012AA092203 ) to S.
AFM analysis AFM analysis was performed in accordance with the method previously described  [32]. Three to five μL of fibril solution was deposited onto a freshly cleaved piece of mica and left to adhere for 30 min. Samples were then washed with distilled water and blow-dried under a flow of nitrogen. Images were collected at a line scan rate of 0. 5-2 Hz in ambient conditions. The AFM free oscillation amplitudes ranged from 25 nm to 40 nm, with characteristic set points ranging from 75% to 90% of these free oscillation amplitudes. AFM data were analyzed with Gwyddion (gwyddion. net) and SPIPTM (www. imagemet. com) software.
Finally, cells were washed 5 times, 5 min/time with PBS, and counterstained with DAPI to reveal nuclei, then mounted in Vectashield Mounting Medium. Cell coverslips were stored at 4°C for confocal fluorescence microscopy. The fluorescence was measured in at least 10 randomly chosen observation fields for each experimental condition using Leica SP5 confocal laserscanning microscope. The increase in fluorescence was measured calculating CORRECTED TOTAL CELL FLUORESCENCE (CTCF) using the formula: CTCF = Integrated density -(Area of selected cell X Mean fluorescence of Background readings) using the ImageJ 1. 47 Software (NIH). Quantification experiments were carried out independently at least three times; more than 150 cells were counted for each condition. Individual differences were assessed using individual student's t-tests in GraphPad Prism software (San Diego, CA).
Sanger sequencing of the MFM genes We had started screening a group of 21 MFM index patients with conventional Sanger sequencing before the NGS panel for MFM was established. We analysed DES, CRYAB, MYOT (exon 2 and 9), FLNC (exon 48), ZASP (exon 4-10), FHL1, BAG3 and DNAJB6. We performed PCR using standard protocols and used the BigDye Terminator v1. 1 mix (Applied Biosystems) for cycle sequencing reactions according to the instructions in the kit. Sequence data were generated with an ABI 3130xl capillary sequencer (Applied Biosystems, Carlsbad, CA, USA) using standard protocols and analysed by GenSearch v. 4. 0. 8 (PhenoSystems, Lillois, Belgium).
Sequence data were analysed with GenSearch NGS v. 1. 4 (PhenoSystems, Lillois, Belgium) automatically aligning data to the reference sequences mentioned above. Variants within exons and 20 bp of the flanking intronic sequences were detected with VarScan (http://varscan. sourceforge. net/) using following filters: coverage >15, frequency >20% for heterozygous or >75% for homo-and hemizygous variants. Candidate variants were verified by Sanger sequencing on an ABI 3130xl automated capillary sequencer using standard protocols, and their effect predicted with bioinformatic tools like PolyPhen-2 (http://genetics. bwh. harvard. edu/pph2/index. shtml), SIFT (http://sift. jcvi. org/) and MutationTaster (http://www. mutationtaster. org/) provided by Alamut (Interactive Biosoftware, Rouen, France).
Sanger sequencing of exon 343 of TTN Finally, we performed Sanger sequencing to analyse exon 343 of TTN in 25 of our index patients, in whom an underlying gene defect had thus far not been identified (21 patients) or only an unknown variant was revealed (4 patients). PCR, sequencing reaction and data analysis of exon 343 of the TTN gene (NM 001267550. 1) have been performed using standard protocols as described above.
One mutation each was found in ZASP, CRYAB and in BAG3 (Table  1 , Figure  1 ). The mutation in BAG3 represents a novel mutation, whereas the other mutations have been described previously. The c. 626C > A, p. Pro209Gln mutation in exon 3 of BAG3 (Patient F13. 1, Table  1 ) is so far not known in the databases of the NHLBI exome sequencing project (ESP) or the 1000 genome project and was predicted to be disease causing by all used prediction programmes. Further arguments for pathogenicity came from familial segregation analysis, in which both healthy parents did not harbour the mutation, indicating a de novo mutation.
Genetic results in our MFM cohort (n = 43): polymorphisms and unclassified variants With means of NGS panel diagnostics we found a large number of variants, especially in FLNC. The suspicious variants with a minor allele frequency beneath 1% are listed in Additional file 1. We assessed these variants with various databases and prediction programmes. Especially the pathogenicity of the c. 6595G > A, p. Gly2199Arg mutation in exon 40 of FLNC (patient F20. 1, Additional file 1) finally remained unclear. This genetic variant has only been counted once by the NHLBI exome sequencing project (ESP) and was predicted to be benign by PolyPhen-2, but disease causing by Mutation Taster. The glycin residue at position c. 6595 is highly conserved, as well as the nucleotide at this position. Unfixed muscle tissue of this patient was not available anymore and no new muscle biopsy could be obtained, so that additional proteomic analyses for possible further clarification could not be performed.
Methodological issue: Sanger versus NGS sequencing In ten of our patients, a mutation in one of the MFMcausative genes was identified using conventional Sanger sequencing. By employing NGS, we additionally found four mutations, among them the novel BAG3 mutation, as well as a lot of variants, especially in FLNC, beyond the mutational hotspot in exon 48. The mass of variants that are found using NGS and their sometimes difficult interpretation can currently still be considered as a drawback of this technique. However, knowledge concerning the variants will increase in the following years as NGS will become more widely available and databases more complete. Advantages of NGS are reduced costs and decreased time to diagnosis. Furthermore, a specific and often unreliable genetic testing sequence is made redundant, especially in diseases with overlapping morphological and/or clinical phenotypes, such as MFM.
Acknowledgements We are grateful to the personnel of the  Institute of Neuropathology  and the  Department of Neurology  at the  RWTH Aachen University hospital, Aachen, Germany , for the technical support. We are thankful to  Birgit Halliger-Keller  of the  Department of Human Genetics at the University of Würzburg, Würzburg, Germany , and  Phillipp Helbig , for their technical support, as well as to  Pauline Lahaut  at the  Nice University Hospital  for her help in collecting patient's data.
We consider the problem of decomposing an image into a cartoon part and a textural part. The geometric and smoothly-varying component, referred to as cartoon, is composed of object hues and boundaries. The texture is an oscillatory component capturing details and noise. Variational models form a general framework to obtain u + v image decompositions, where cartoon and texture are forced into different functional spaces. The TV-L1 model consists in a L 1 data fidelity term and a Total Variation (TV) regularization term. The L 1 norm is particularly well suited for the cartoon+texture decomposition since it better preserves geometric features than the L 2 norm. The TV regularization has become famous in inverse problems because it enables to recover sharp variations. However, the nondifferentiability of TV makes the underlying problems challenging to solve.
[31] , Strong et al. [30] ) is rich (Aubert et al. [1] , Vese et al. [33] , Green  [16] , Osher et al. [25] ). Hybrid models with wavelets are described in the papers by Malgouyres  [20]  and Lintner et al. [19]. We present in this paper an implementation of the TV-L1 model, where the L 2 norm is replaced by the L 1 norm. Non differentiable data like L 1 terms were inaugurated by Nikolova  [23] , and then studied by Chan and Esedoglu  [9]. Many aspects of the TV-L1 model were covered in the literature: applications to outliers and impulse noise removal (Nikolova  [24] ), study of the TV-L1 model from a geometric point of view (Duval et al. [11] , Yin et al. [37] ), connection with mathematical morphology (Darbon  [10] ) and cartoon-texture decomposition (Aujol et al. [3] , Haddad  [17] , Yin et al.
Another class of algorithms is based on the augmented Lagrangian method (ALM), which is applied to TV-L1 restoration by Zhang and Tai  [35]. A variant is the alternating direction method (ADM)  [32]. The main idea of ADM is to reformulate a TV problem as a linear equality constrained problem where the objective function is separable and then minimize its augmented Lagrangian function. An online implementation of ADM is available at http://www. caam. rice. edu/ ~optimization/L1/RecPF/. A Matlab implementation of Chambolle's primal dual algorithm applied to image decomposition with a stationary noise assumption  [12]  is also available at : http: //www. math. univ-toulouse. fr/ ~weiss/PageCodes. html. The rest of the paper is organized as follows: in Section 2, we present Chambolle's primal dual algorithm applied to the cartoon+texture decomposition problem and discuss the role of the parame-ters.
Dependencies The code provided is a stand-alone C++ code, available at https://doi. org/10. 5201/ipol. 2014. 81. It uses the C++ standard template library extensively. The user can choose between the singlethreaded implementation and its parallel version. The single-threaded version does not rely on any external libraries. The parallelization is done through OpenMP 2  , a standard API for shared memory multiprocessing programming. The code was tested successfully on Ubuntu 12. 04, 12. 10 and Debian 6. 0. 7 with g++ 4. 4 or 4. 7, and on MacOs 10. 8 using g++4. 8. 0. The compilation is done through the CMake build system to be cross-platform. The code compiles with g++ and with clang, but there is no support for OpenMP with the clang compiler, so that the parallelism is deactivated in that case.
Standard Shapes (Stanford Repository) The Stanford Bunny contains 10 scans and 362000 oriented points. Bernardini et al. proposed to use a series of three radii (0. 3, 0. 5 and 2 mm, the shape being bounded in a box of size 150mm). The pointset is obtained from the Stanford repository and a mean curvature motion is applied to filter the point positions as described in the paper by Digne et al. [5]. We also use a single scan containing 1568548 points from another standard shape: the Stanford Dragon. We show the result obtained by using multiple radii (0. 3, 0. 5 and 1mm). Both of these reconstructions are shown in Figure  10. The last displayed shapes come from the Farman dataset, a high resolution freely available dataset. The pyramid is a subsampled oriented version of the original dataset, containing only 1 million points (Figure  11 ).
MLMT-PCR analysis Exact size of the PCR fragments was established by using a capillary sequencer and the Gene Mapper software v 3. 2 (ABI). Fluorescence labeled PCR products were separated using a gel capillary electrophoresis. In some cases, a double peak with only one base difference was obtained due to an A-overhang created during PCR. Hence, only one peak was scored. Fragment sizes for each isolate assessed for the ten microsatellite markers were estimated using the Gene Mapper software and the repeats number was calculated based on the number of repeats of the respective marker in L. major MHOM/IL/1980/Friedlin strain (considered as theoretical size). Repeats numbers estimated for the ten loci were assembled into a multilocus microsatellite profile for each used isolate  [21, 27, 28].
Data analysis Microsatellite based genetic distances were calculated using MSA and POPULATIONS softwares by applying different distance measures appropriate for microsatellites  [21]. MSA software package 4. 05 (http://i122server. vu-wien. ac. at/MSA/ MSA_WIN. html) provides a variety of format outputs used for the analysis of microsatellite data  [29]. The distance matrices generated by POPULATION software v1. 2. 32 (http://www. bioinformatics. org/groups/?group_id = 84) allowed the construction of a Neighbor-Joining (NJ) tree with bootstrap values through the Dps (proportion of shared alleles) measure method to analyze the MLMT results using the MEGA 4 tool v 4. 0. 2 [30, 31]. STRUCTURE software  [32]  was applied to calculate microsatellite genetic distances according to the proportions of shared allele distance measurements.
Microsatellite analysis MLMT PCR was performed on all strains using a set of ten informative microsatellite markers. For each one of the latter, PCR products of studied strains were controlled on 2% agarose gel and showed the same molecular weight (data not shown). Theoretical size of amplified fragments obtained show a difference between Friedlin reference strain and isolates obtained from Tunisian rodents in eight, out of ten microsatellites (Table  1 ). Tunisian strains had the same size as Friedlin for two markers (27GTG and 36GTG), rather. On the other hand, all these isolates showed the same amplified fragment size whether they were obtained from P. obesus, M. shawi or M. nivalis species indicating a homogeneous genotype for all isolated strains. Accordingly, MLMT did not reveal any polymorphism within these strains.
LAVA insertions in the gibbon genome The gibbon genome contains all previously described classes of transposable elements that are mostly also present in other primates. One exceptional addition is the LAVA element, a novel retrotransposon that emerged exclusively in gibbons  12  and has a composite structure comprised of portions of other repeats (39-L1-AluS-VNTR-Alu -like -59) (Fig. 3a ). Searches of Nleu1. 0 retrieved 1,797 LAVA insertions, 1,256 of which were 39 intact elements, many carrying signs of target-primed reverse transcription (TPRT)  13. The distribution of 39 intact LAVA elements uncovered a significant overlap with genes (Pearson chi-squared, P 5 0. 017) and Gene Ontology (GO) analyses using the database for annotation, visualization, and integrated discovery (DAVID)  14  showed a significant functional enrichment exclusive to the 'microtubule cytoskeleton' category (false discovery rate 5 0.
031, P value 5 0. 001) (Supplementary Information section S7 and Supplementary Data File 6) (Extended Data Fig. 3 ). Additional analyses with meta-pathway database tools  15, 16  refined this enrichment to pathways related to chromosome segregation, including 'establishment of sister chromatid cohesion' and 'mitotic metaphase and anaphase' (Supplementary Table  ST7. 3). Genes with LAVA insertions include proteins that function as checkpoints for cell division and for spindle integrity/architecture (such as MAP4, CEP164 and BUB1B)  [17] [18] [19]  , participate in kinetochore assembly and attachment to the spindle (for example, MAD1L1 and CLASP2)  20, 21  , and have a role in chromosome segregation during cell division (for example, KIFAP3 and KIF27)  22  (Extended Data Table  1 ). Intragenic LAVA insertions were skewed toward introns (Pearson chi-squared, P 5 0.
1-7. 2). We used a maximum likelihood method  27  to obtain age estimates for the 22 LAVA subfamilies. In the case of the two oldest subfamilies, LAVA_A1 and LAVA_A2, we obtained estimates of ,18 Myr ago and ,17 Myr ago, respectively (Supplementary Table  ST7. 3). A coalescent-based methodology implemented in the software G-PhosCS 28 using Nleu1. 0 estimated a gibbon-great ape population divergence time of ,16. 8 Myr ago (95% confidence intervals (CI): 15. 9-17. 6 Myr ago) assuming a split time with macaque of 29 Myr ago (Supplementary Information section S4). Hence, the LAVA element probably originated around the time of the divergence of gibbons from the ancestral great ape/human lineage. The evolutionary history of the gibbon lineage and, in particular, the timing and order of splitting among the four genera, is still a subject of debate  29.
METHODS SUMMARY Sanger-based whole-genome sequencing was performed as described for other species. The genome assembly was generated using the ARACHNE genome assembler assisted with alignment data from the human genome (Supplementary Information section S1). The source DNA for the sequencing was derived from a single female (Asia; studbook no. 0098, ISIS no. NLL605) housed at the Virginia Zoo in Norfolk, Virginia. Short-read libraries were constructed at the Oregon Health & Science University (OHSU) following standard Illumina protocols and sequenced on an Illumina HiSeq 2000. Analyses were performed with custom analysis pipelines. See Supplementary Information for additional information about the methods. Extended Data Figure  1  | The gibbon assembly statistics and quality control. a, The table compares the gibbon assembly statistics to those of other primates sequenced with a similar strategy.
Acknowledgements The gibbon genome project was funded by the  National Human Genome Research Institute (NHGRI)  including grants  U54 HG003273  (R. A. G. ) and  U54 HG003079 (R. K. W. )  with further support from  National Institutes of Health NIH/NIAAA   P30 AA019355  and  NIH/NCRR   P51 RR000163  (L. C. ),  R01_HG005226  (J. D. W. , M. F. H. ),  NIH P30CA006973  (S. J. W. ), a fellowship from the  National Library of Medicine Biomedical Informatics Research Training Program  (N. H. L. ),  R01 GM59290  (M. A. B. ) and  U41 HG007497-01  (M. A. B, M. K. K. ),  R01 MH081203  (J. M. S. ),  HG002385  (E. E. E. ),  National Science Foundation (NSF )  CNS-1126739  (B. U. , M. A. B. , M. K. K. ) and  DBI-0845494  (M. W. H. ),  PRIN 2012  (M. R. ), Futuro in ricerca 2010 RBFR103CE3 (M. V. ),  ERC   Starting Grant  ( 260372 ) and  MICINN (Spain)   BFU2011-28549  (T.
Results miR-491-5p induces apoptosis in IGROV1-R10 cell line and inhibits cell growth of SKOV3 cells. To identify potential miRNAs that could induce apoptosis in ovarian cancer cell lines, we performed an in silico search for putative miRNAs that could target BCL-X L using miRNA targetprediction tools  16  (Supplementary Figure  S1 ). Among them, we focused on those that may also target MCL1. Each of the 11 selected miRNAs was transfected into two chemoresistant ovarian carcinoma cell lines (IGROV1-R10 and SKOV3) and cell proliferation was analysed (Supplementary Figure  S2 ). We focused on miR-491-5p because it was found to be the most efficient cell growth inhibitor and was not expressed in both cell lines (personal data from miRNA profiling experiments). The biological effect of miR-491-5p on both ovarian cancer cell lines was analysed in real-time with the xCELLigence system by following Cell Index (CI) over a period of 100 h.
40 CI values are derived and displayed in the plot. Briefly, 7 × 10 3 cells/well IGROV1-R10 or 3. 5 × 10 3 cells/well SKOV3 were plated in 96-well E-Plate View and placed onto the Real-Time Cell Analyzer multi-plate located inside a tissue culture incubator. Cells were left to grow for 24 h before treatment and impedance was continuously measured until the end of the treatment. Standard deviations of well replicates were analysed with the RTCA software. RNA isolation and TaqMan gene assays. Total RNA was isolated from transfected cells using Trizol (Invitrogen). RNA quantity and quality were assessed using the NanoDrop 2000 spectrophotometer (Thermo Scientific, Palaiseau, France). The expression of BCL-X L and GAPDH transcripts were determined by RT-qPCR. The first strand cDNA was synthesized using Omniscript reverse transcriptase kit (Qiagen, Courtaboeuf, France) with random hexamers.
Corresponding custom designed (forward, 5′-tgcgtggaaagcgtagacaa-3′; reverse, 5′-aggtaagtggccatccaagct-3′; probe 5′-FAMagatgcaggtattggtgMGB-3′) and inventoried (Hs99999905_m1 for GAPDH) TaqMan Gene Expression Assays were used (Applied Biosystems, Life Technologies). GAPDH was used as a housekeeping reference gene for normalization. For expression quantification, PCR amplification was performed in triplicate in an ABI 7500 Fast Real-time PCR system (Applied Biosystems, Life Technologies). Data are representative of three independent experiments performed in triplicate and no-template controls were included for each assay. The 2 -ΔΔCq method was used to calculate relative changes in gene expression determined from real-time quantitative PCR experiments. 41 Data are presented as the percentage of untreated cells and as means ± S.
MCL1 (S19) was from Santa Cruz Biotechnology (Le Perray en Yvelines, France). Appropriate horseradish-peroxidase-conjugated secondary antibodies (CST or GE HealthCare Europe GmbH, Velizy-Villacoublay, France) were used and signals were detected using enhanced chemiluminescence (GE HealthCare Europe GmbH). Blots were also hybridized with β-actin (Eurobio, Courtaboeuf, France) or α-tubulin (Sigma-Aldrich) monoclonal antibodies to control protein loading. Each immunoblot is representative of three distinct experiments. In some cases, protein expression was measured by quantifying the density of immunoblots bands adjusted to β-actin (image analysis software ImageJ). Phosphatase treatment. Exponentially growing cells were transfected or not by miR-491-5p or miR-Ctrl as described above. After 48 h incubation at 37 °C, the cells were detached from the plates by trypsinization, pelleted, washed with PBS and lysed on ice with a RIPA buffer without phosphatase inhibitors.
Acknowledgements. We thank  Marilyne Duval  ( Flow cytometry Core Facility, Federative structure 4206 ICORE of the University of Caen Lower Normandy ) for technical help. We also thank  Nathalie Leiber  ( Comprehensive Cancer Center F. Baclesse, Pharmaceutical Service, Caen ) for providing cetuximab. We also thank  Monique Verhaegen  ( University of Michigan ) for critical reading of the manuscript and useful suggestions. NV is a recipient of a doctoral fellowship from the  French Ministry for Higher Education and Research. This work was supported by a grant from l 'Ecole de l'Inserm Liliane Bettencourt (NV). CL is a recipient of a doctoral fellowship from the  'Ligue Contre le Cancer ' (Calvados committee). This work was supported by the  « Ligue Contre le Cancer » (Calvados's and Orne's committees) , the  'Conseil Reǵional de Basse Normandie' , the  French Government  and the  European Community (Fonds Européens pour le Développement de la Recherche-FEDER).
Study of Cell Death and Cell Proliferation by Flow Cytometry. Confluent HUVECs were either treated or not treated with native LDL or Mox-LDL at a final concentration of 100 g/mL for 24 hours. Cell death was detected using the LIVE/DEAD Fixable Red Dead Cell Stain Kit (Molecular Probes; Cat. number L-23102) following manufacturer's instructions. HUVECs were harvested and stained with the near-IR Dead Cell Stain which is excited at a 633/635 nm wavelengths. For proliferation analysis, BD Pharmingen Ki67 kit was used and the assay was also performed according to manufacturer's instructions. In brief, after staining with the Red Dead Cell Stain, cells were fixed, permeabilized, and then stained with FITC-Ki67 (BD Pharmingen, San Diego, CA, USA; Cat. number 612472) for 20 min at 4 ∘ C. Cells were then analyzed using BD FACSCanto II flow cytometry, and data were analyzed using FlowJO (Tree Star, inc.