dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments We thank  Francesca Cole  and other members of the  Jasin laboratory, Patrizia Alberti and Loic Ponger from the laboratory of ''Regulation and Dynamics of Genomes '' at  MNHN , and  Alexei Morozov in Malcolm Moore's laboratory at MSKCC  for helpful discussions. We also thank  Fyodor Urnov  ( Sangamo BioSciences, Inc. ) for his help in initiating the project. M. P. is supported by a '' Le Canceropole IDF '' PhD grant and H. G. is supported by a '' La Ligue Nationale contre le Cancer '' PhD grant. This work was supported by  CNRS ,  Inserm ,  MNHN ,  IBiSA (Infrastructures for Biology) , and  ANR-12-JSV6-0005-01  (E. B. ) and by grant  R01 NIHGM54668  (M. J. ). Author contributions: E. B. and M. J. designed the research. M. P. , H. G. , A. D. C. , L. G. , M. T. , L. P. , O. R.
Acknowledgments-We thank  Dan Finley  ( Harvard Medical School, Boston, MA ) for the SUB strains,  Catherine Dargemont  ( Institut Jacques-Monod (IJM), Paris, France ) for the His 6 -Ubc4 plasmid, and  Batool Ossareh-Nazari  (IJM) and  Damien Abreu  for initial help in setting up the in vitro ubiquitination assays.
This work was funded by grants from  Agence Nationale pour la Recherche  [ ANR-07-PHYSIO-010-01 ];  Region Pays de la Loire  [CIMATH-2]; INSERM; and  Université d'Angers. VGM and MLM are recipients of postdoctoral fellowship from  Université d'Angers and Société Française de Hypertension Artérielle , respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Western blot Protein extracts were prepared as described in  [31]. Proteins were resolved in 4-12% bis-Tris gels and transferred onto nitrocellulose. Proteins were detected using antibodies specific for IDE (clone 9B12; a generous gift of R. A. Roth, Stanford Univ. ), phospho-Akt substrate (including p27; Cell Signaling, Danvers, MA, USA) and Hog1 (Santa Cruz Biotechnology, Santa Cruz, CA, USA) as loading control. Quantification of bands was done using ImageJ software.
Metacaspase activation Cells were treated with 10 mg/ml of TU for 45 min, collected, suspended in fresh medium without TU and incubated at 30uC with agitation. At 0, 4 and 6 hours from release, cells were processed as described in  [32]  to assess metacaspase activation using the fluorescent probe FITC-VAD-FMK (CasPACE, Promega, WI, USA). Fluorescence was detected with a FACSCalibur flow cytometer (Becton Dickinson, NJ, USA) as described in  [32]  and data analyzed using CellQuest software.
3B ). In addition, titration of the digestion reaction with increasing concentrations of 1, 10-phenanthroline, a metallopeptidase inhibitor, shows that the two enzymes are inhibited to an almost identical extent (Fig. 3C ). Addition of increasing concentrations of Zn 2+ to the fluorogenic peptide digestion had an equivalent inhibitory effect for both enzymes (data not shown). Next, we sought to determine whether Iph1 is able to cleave insulin, the hallmark natural substrate of hIDE cleaved with high efficiency by it. We performed insulin digestions with various amounts of enzyme and analyzed the results by column and gel chromatography. After 16 h of digestion with either 500 ng hIDE or 800 ng Iph1, the insulin peak was no longer detectable in reversed phase chromatography and various new product peaks appeared on the chromatogram (Fig.
Acknowledgments We thank  FX. Real, MD ,  R. Gasa, PhD , and  MJ. Parsons, PhD  for valuable comments to the manuscript,  M. Rodrı ´guez-Rivera  for her assistance,  J. Ferrer, MD , and  M. Garcı ´a, PhD , for providing us with some of the antibodies used in this study, and  M. Pulido, MD , for editing the manuscript.
We then performed BD simulations of yeast chromosome dynamics in a volume the geometry of which is consistent with yeast nuclear size, and using the structure derived from Hi-C experiments as the initial state  (Duan et al. 2010). We assumed that chromosomes were attached to the SPB at their CEN (i. e. , neglecting the contribution of microtubules connecting SPB to kinetochores), and freely diffusing at their TEL (chromosome III is represented in the left panel of Fig. 4B ). The computed MSD for loci distant from CEN (>400 nm; blue data set in the right panel of Fig. 4B ) reproduced the anomalous diffusive response associated with a powerlaw scaling of ;0. 54 over a temporal domain of four orders of magnitude that we observed experimentally (dashed line in Fig. 4B , right panel). The motion is more restricted for segments located at 10-100 nm from the CEN (pink data set) versus at a distance comprised between 200 and 400 nm (red data set).
The polymer is elongated, and its diameter is ;300 6 50 nm. The MSD is computed for loci localized near the SPB, or at 200-400 nm and more than 400 nm from this anchor (purple, red, and blue data sets, respectively), showing that the response follows Rouse dynamics (black dashed line) provided that the locus is sufficiently distant from CEN. we wished to strengthen our conclusions by running BD of a single chain composed of self-avoiding segments (see Model section). The extracted MSD shows an anomalous diffusive response, as well as the dependence on the persistence length and the viscous drag (Eq. 2) expected from the Rouse model (Fig. 5B ). This analysis showed that the numerical prefactor of Equation 2 is underestimated by 1. 4, suggesting that volume exclusion enhances the rate of spatial exploration.
We used the Langevin dynamics algorithm implemented in the NAMD software  (Phillips et al. 2005 ) with an appropriate inhouse force field. The Langevin equation for the nth monomer has the form: m n d 2 x n dt 2 t ð Þ ¼ Àgrad xn E þ f n t ð ÞÀm n b n dx n dt t ð Þ; ð6Þ where the random force f n (t) is derived from a Gaussian distribution with the properties: AE f n t ð Þae ¼ 0 ð7Þ AE f n t ð Þf n 0 ð Þae ¼ 2k B Tzm n d t ð Þ; ð8Þ with z the friction coefficient. The energy E of each bead is the sum of three contributions associated with the confinement in the nucleus, the elasticity of the chain, and the repulsive interactions between monomers, which are expressed as: E ¼ E conf þ E spring þ E VdW ð9Þ E conf r < r 1 ð Þ¼0 and E conf r > r 1 ð Þ¼E 1 rÀr 1 ð Þ 4 ; ð10Þ with r the distance of the bead to the center of the nucleus, and r 1 the radius of the nucleus.
Live cell imaging Yeast cells were imaged at room temperature with a BX-51 upright microscope equipped with a laser diode (Lumencor), a 1003 oil immersion objective (NA = 1. 4), and an EMCCD camera (Andor DU-897), as described in  Hajjoul et al. (2009)  (see Supplemental Video 1). The excitation emission at 470 6 10 nm was set to 7. 53 W/mm 2 , about 100 times less than the value that is necessary for normal cell growth  (Carlton et al. 2010 ), and we observed consecutive rounds of divisions during ;2 h (data not shown). For slow acquisitions of interframe intervals of 2 sec or more, we used a 1003 oil immersion objective with a variable NA set to ;1. 1-1. 2. The acquisition was performed with a shutter synchronized with the camera to minimize photobleaching, and we checked for drifts by monitoring the position of the center of the nucleus in the first and last image of the recording.
Optimal interframe intervals of ;20 msec were reached by cropping regions of interest and using a 2 * 2 binning with the Andor iQ imaging software. The loss in pixel size resolution was compensated with a 23 lens placed in the microscope light path. We focused on 2D single-particle tracking and checked that similar information was retrieved with 3D tracking using micromirrors (Supplemental Fig. S3 ;  Hajjoul et al. 2009 Hajjoul et al. , 2011)). We note that 2D acquisitions may bias MSD responses for loci preferentially localized at the periphery, because in some cases central loci in the projected view may be peripheral in the 3D nucleus.
Data analysis Video sequences consisted of 300 consecutive images, and we displayed MSD traces on 150 time intervals at most in order to ensure the statistical relevance of mean displacements. The movements of chromosome loci were systematically analyzed using a custom software that was developed in Matlab (Mathworks)  (Sergeet al. 2008; Albert et al. 2013  [source code at http://jcb. rupress. org/ content/202/2/201/suppl/DC1, and the executable file at ftp:// intermtt:MTTinterface@ftp. laas. fr/]). This software enabled us to extract (x, y) coordinates by Gaussian fitting, to reconstruct the trajectories, and to compute the MSD and the step distribution function (see Supplemental Video 1). Note that the MSD in fixed cells was 20-to 30-fold lower than in living cells (Supplemental Fig. S3B ).
2010). Chromosomes are tethered at their centromeres (green spheres) and free at their telomeres. The figure in the left panel represents the orthographic projection of 100 conformations of chromosome III in the course of one simulation of 10 6 time points. The polymer is elongated, and its diameter is ;300 6 50 nm. The MSD is computed for loci localized near the SPB, or at 200-400 nm and more than 400 nm from this anchor (purple, red, and blue data sets, respectively), showing that the response follows Rouse dynamics (black dashed line) provided that the locus is sufficiently distant from CEN.
Acknowledgments We thank the  University Paul Sabatier for Ph. D. fellowship funding  (to J. M. ). This work was partly supported by the  ANR  program  JC08_341867 , by the  CNRS program PIR , and by the  LAAS-CNRS  technology platform, a member of the  French Basic Technology Research Network. We are grateful to  Nathalie Daigle  for critical reading of the manuscript. We are grateful to  Charlotte Galimow  for strain construction and initial characterization of gene position.
En él se destacan las implicaciones relevantes para las regiones del mundo en las que la incidencia del cáncer de mama en los próximos años hará del tamizaje poblacional una opción para el control del cáncer. Palabras clave: programa de tamizaje organizado; mamografía; cáncer de mama; control de calidad A ccording to estimates based on the Globocan database,  1  cancer of the breast is the most common cancer, and the most common cause of death from cancer in women worldwide (figure  1 ). Demographic trends indicate a continuing increase in this substantial public health problem, particularly in the world's less developed regions. * Worldwide 1. 38 million new cases (23% of all cancers in women) and 458 000 deaths due to breast cancer (12. 7% of all cancer deaths in women) were estimated in 2008.
Acknowledgements The preparation of this report and the activities described therein have received financial support from the  European Commission  [grant agreement. No  2004309 ,  European Cancer Network ; No. 2004114 (ECN),  European Network for Information on Cancer (EUNICE) , and No. 2006322 ,  European Cooperation on Development and Implementation of Cancer Screening and Prevention Guidelines (ECCG) ]. The present article is a slightly modified version of the original manuscript submitted in August 2010 for publication in a special issue of SPM.
In these conditions, the dissociation constant (Kd) of this dimer was measured using isothermal titration calorimetry (ITC) as being around 10 μM (Figure  1D ). Structure determination of the FIV full-length p15 protein by X-ray crystallography FIV full-length p15 protein at 6 mg/ml in MES buffer pH 6 crystallizes in the presence of sodium acetate pH 4. 6 and PEG in the space group P2 1 2 1 2 with one molecule in the asymmetric unit. Synchrotron data were collected to 2 Å resolution. The phase problem was solved by molecular replacement using SIV p17 (PDB ID: 1ECW) as the search model  [32]. The FIV p15 structure was refined to a final R work of 19% (R free = 25. 5%) (Table  1 ). The structure consists of five α-helices (numbered h1 to h5 following the HIV convention), which give rise to the close packing of adjacent helices typical for retroviral matrix proteins (Figure  2A ).
Indeed, the Cterminal region following helix h5 is extended in the FIV p15 structure, which is in line with what has been demonstrated for EIAV  [31] , where the flexible C-terminus is not observed in the electron density map. In contrast, a structured C-terminus with a short β-hairpin is observed in  SIV MA  [32]  and with a long helix h5 in HIV MA  [13]  (Figure  3 ). However, the structures of HIV MA, as determined by NMR (PDB ID: 1HMX and 1TAM), indicate that this region is disordered  [30, 46]. Thus, the extended conformation of the FIV p15 C-terminus could represent a biological feature of the protein, and the well-ordered structures of the HIV and SIV p17 C-terminus could represent crystallization artifacts  [47]. This is underlined by the fact that the C-terminal portion of MA is not compactly folded in Gag virus-like particles  [48, 49].
Plasmid constructs The FIV p15 open reading frame of the Petaluma strain (GenBank accession number: M25381. 1) was amplified from 0. 1 μg of the plasmid FIV-34TF10 obtained through the NIH AIDS Research and Reference Reagent Program. For the PCR amplification of the full-length protein, we used the forward primer (5'-CATATGGGGAATGG ACAGGGGCGAGATTGG -3', NdeI site underlined), and the reverse primer (5'-AGATCTTCAATGATGATG ATGATGATGCTCGAGTGAACCTCTTGG-3') using the Phusion PCR kit (Finnzyme) according to the manufacturer's protocol, with 25 cycles of PCR and a hybridization temperature of 50°C. A truncated form of the p15 protein (p15-Δ120) was obtained using the same procedure, with reverse primer 5'-GCTCGAGTGAACCTCTTGGAACC AGAGATGGCCTAGTGTCTAATC-3'. A second PCR round was performed on all constructs with the same forward primer and with reverse primer 5'-AGATCTT CAATGATGATGATGATGATGCTCGAGTGAACCTC TTGG-3' introducing the Bgl2 site (underlined) as well as a C-terminal 6-His Tag.
SEC-MALLS experiments To verify the oligomeric state of the protein in solution, FIV p15 was analyzed using a SEC-MALLS (size-exclusion chromatography with multi-angle laser light scattering). We loaded 0. 2 ml samples of p15 protein at 6 mg/ml in 50 mM MES pH 6, onto a Superdex 200 10/30 gelfiltration column equilibrated at 0. 5 ml/min with 50 mM MES pH 6. The eluate was passed successively through a MiniDawn TREOS-angle light scattering detector (Wyatt) coupled to an Optilab T-rEX refractive index monitor (Wyatt). The data were processed, and molecular masses were calculated using the Astra V software (Wyatt).
Crystallization of the FIV p15 protein and data collection Crystallization conditions were searched using the sittingdrop vapour-diffusion method and commercial kits from Hampton Research, Molecular Dimensions Limited (MDL) and Qiagen. Crystals of FIV p15 were obtained by equilibrating drops of protein (concentrated at 7 mg/ml in 50 mM MES buffer pH 6) mixed 1:1 with the condition 25 of the Qiagen PEGs Suite, consisting of 0. 1 M sodium acetate pH 4. 6 and 25% (w:v) polyethylene glycol (PEG) 3,000 at 16°C. Tiny rod-shaped crystals with maximum dimension 60 × 30 × 10 μm 3 were obtained within fifteen days. Crystals were transferred to a cryoprotective solution containing the mother liquor and 10% (v:v) ethylene glycol for 30 sec and plunged into liquid nitrogen prior to data collection. First grown crystals diffracted at best to 3 Å resolution at the SLS beamline PXIII (Villigen PSI, Switzerland) and at the ESRF beamline ID23-2 (Grenoble, France) under cryo-conditions (100 K).
Microseeding was necessary to optimize crystals and the best dataset was collected at 100 K to 2 Å resolution at the SOLEIL beamline Proxima 1 (Paris, France). A new crystallization condition was determined for the p15-Δ120 construct. Crystals were obtained in 0. 1 M Tris pH 8, 25% (w:v) PEG 6000 (condition 45 of the Qiagen PEGs suite). Crystals were harvested as for the full-length protein and data were collected at 100 K to 2. 7 Å resolution at the ESRF beamline ID29.
Structure determination of FIV p15 and refinement Diffraction intensities were processed with the programs XDS  [58]  and XSCALE. The structure of full-length p15 was determined by the molecular replacement method using the program MrBUMP  [59]  of the CCP4 program suite and the structure of SIV matrix protein (PDB ID: 1ECW) as the search model. Final automated building was performed with ARP/wARP  [60] , which built 95% of the residues present in the final model. Crystallographic refinement was performed with PHENIX  [61]  and residues 119-129 were built manually using COOT  [62]. The final model is made up by one copy of FIV p15 (chains A, residues 4-133), 4 molecules of ethylene glycol and 28 water molecules. The model shows a good geometry with 2 glycine residues as Ramachandran outliers.
Figures were generated with the PyMOL software from Schrödinger. The electrostatic potential map and the molecular surfaces were calculated using DelPhi  [63]. Structure of p15 truncated mutant p15-Δ120 was determined using the full-length p15 structure as a lead. The 2 N-terminal residues of p15 could be manually reconstructed using COOT. Two PEG molecules were identified and positioned in the electron density maps using PHENIX and the 7PE ligand coordinates from the PDB as a template. The final model is made up by two copies of p15-Δ120 (chains A and B, residues 2 to 120), 2 molecules of PEG (chains P and Q) and 24 water molecules. This structure shows a good geometry with no Ramachandran outlier. Statistics of the X-ray data are provided in Table  1.
Docking studies Molecular docking of the myristoyl group (as ligand) against p15 crystal structure (the receptor) was done using molecular docking program AutoDock 4. 2. 3  [64, 65]. Both molecules were prepared with AutoDockTools 1. 5. 4  [65]  by adding all essential hydrogen atoms and assigning Gasteiger charges. All the 12 active torsions of the ligand were taken into account for the subsequent calculations. Finally, 6 amino acid residues were defined as flexible for the receptor, namely Trp9, Cys16, Phe35, Ile39, Ile53 and Phe90. A grid box of dimensions of 20 × 20 × 20 Å 3 (with a grid spacing of 0. 159 Å), large enough to encompass the pocket, was calculated using the AutoGrid program. Lamarckian genetic search algorithm was employed and a maximum of twenty-five million energy evaluations was performed.
Alignment of sequence of retroviral matrix proteins The sequences alignment between retroviral matrix proteins was carried out using the web tool ESPript/ENDscript  [66, 67]. The best structural homologues are the EIAV p15 protein (PDB ID: 1HEK), the HIV p17 protein (PDB ID: 1HIW) and the SIV p17 protein (PDB ID: 1ECW) with 21%, 18% and 11% of sequence identity with the FIV p15 protein.
Acknowledgements The crystallization work benefited from the IBCP/UMS 3444 Crystallogenesis facilities and Biophysical platform facilities of  SFR Biosciences Gerland-Lyon Sud. We thank  R. Monserret  and  H. Yajjou  for technical assistance with ITC and protein production, respectively. We also thank  Dr. P. Legrand  ( SOLEIL beamline Proxima 1, Paris, France ) for his help during data collection and his helpful suggestions, and all the staff at the  SLS beamline PXIII (Villigen PSI, Switzerland)  and  ESRF  beamline  ID23-2  and  ID29 (Grenoble, France)  for their technical advices. The research leading to these results received funding from the  European Community 's  Seventh Framework Program  ( FP7/2007-2013)  under grant agreement n. °283570 (BioStruct-X). J. S. was the recipient of a grant from the  Ministère de l'Enseignement Supérieur et de la Recherche.
31-2. 0 (2. 29-2. 0) 19. 68-2. 7 (3. 40-2. 7) Number of unique reflections 7,647 (2,357) 6,138 (1,571) Rwork (%) 19. 05 (21. 11) 21. 51 (23. 48) Rfree (%) 24. 60 (25. 72) 27. 87 (30. 02) Number of protein atoms 1,032 1,808 Number of water/ethylene glycol molecules/PEG molecules 28/4/0 24/0/2 Mean B-factor (Å 2 ) 19. 40 27. 65 Coordinate deviations RMSD bond lengths (Å) 0. 006 0. 002 RMSD angles (°) 0. 930 0. 417 Ramachandran plot Favorable (%) 96. 88 96. 15 Allowed (%) 3. 12 3. 85 Disallowed (%) 0. 00 0. 00 PDB ID 4IC9 4ICA Outermost shell values are indicated in parentheses.
In a study from Japan published in this issue, only 2 of 13 cases of HCA described were found in women taking OC. Presently there is no data concerning the influence of the OC generation on the incidence of HCA. It was thought that the lower levels of estradiol should decrease the risk of HCA. This was not observed. The possible explanation comes from the identification of novel risk factors, namely, obesity and metabolic syndrome. Exploring the combined experience of US centers, publications reporting HCA in the US were identified through a PubMed search and a review of the literature. Whereas earlier reports of HCA in the US described cases exclusively in women exposed to OC, there is a trend towards an increase in HCAs reported in men, HCAs in the absence of OC use, and increased reports of multiple HCAs.
Study sites and field data collection Data were collected in two GA islands, Puerto Rico (PR) and the Guana Island in British Virgin Islands (BVI), and six LA islands: Saint Barthelemy (SB), Guadeloupe (GUA), Terre de Haut island in Les Saintes (SAIN), Martinique (MAR), Saint Lucia (SL) and Barbados (BAR) (Figure  1 ). The islands sizes ranged from 3. 4 km 2 (BVI) to 8870 km 2 (PR). Geographical distances between islands were measured with GOOGLE EARTH (http://earth. google. com) to the nearest kilometre, with distances ranging from 11 km (GUA-SAIN) to 836 km (PR-BAR) (Figure  1 ). Zenaida Doves were caught using walk-in baited drop traps, single-catch closing net bird traps, or mist nets. Blood samples for DNA analyses were taken by puncture of the brachial vein and conserved in storage buffer (70% absolute ethanol, 30% TE pH 8).
, Korea) for sequencing according to the Big Dye Sequencing protocol (Applied Biosystems 3730xl). Sequences were edited and aligned manually using MEGA (v 5. 05. ,  [48] ) leading to 627 bp long sequences with no indels or stop codons. Haplotypes were deposited in GenBank (Accession JN639022-32). A total of 296 individuals (Figure  1 ) were genotyped at 13 microsatellite markers (Table  S1 ) developed for Z. aurita  [45]. PCR conditions for all three types of markers (sex, mtDNA and microsatellites) were as described in  [45]. Microsatellite alleles were visualized on 6. 5% acrylamide 41 cm long gels on a LICOR 4200 L automated sequencer and scored independently by eye by two persons. Reference individuals were included for inter-gel calibration.
Non overlapping 95% CI values and P ST. F ST are expected if directional selection is acting on morphological characters in addition to drift and restricted gene flow  [82] ,  [87]. Statistical analyses were performed using the R software (v. 2. 12. 1,  [88] ), implemented with the packages: mclust (model-based cluster analysis for Gaussian mixture models), mutoss (BY's corrections), rptR (repeatability estimation,  [76] ), and bootstrap (95% confidence interval bootstrapping).
macroura, Z. graysoni, Z. Table  2. Detection of first generation (F 0 ) migrants assessed by GENECLASS 2 of Zenaida Dove (Zenaida aurita) as a percentage of individuals (absolute number in parenthesis) assigned to a putative island of origin given the island were individuals were sampled in. auriculata and Z. galapagoensis) to be a maximum of 2 Myr ago. This time is also likely to represent the time of first colonisation of Z. aurita into the Caribbean, but no definitive evidence is currently placing the root of the Zenaida genus being outside the Caribbean. Data from the same study allow estimating the COI molecular clock at 2% divergence Myr 21 for the genus Zenaida  [44]. Therefore, the mean allopatric divergence between the GA and the LA lineages within Z. aurita in our present study being 0.