dataesr/scientific-paragraphs-categorization huggingface dataset:
BMP-7 nanoreservoirs can accelerate in vivo bone regeneration and mineralization To further study matrix synthesis and bone induction, implantations were carried out in vivo in mice. NF and NR4 nanofibrous PCL thick scaffolds were implanted into mouse calvaria defects for 15 or 30 days. At these times, mice were sacrificed and histological study was then carried out to analyze the host cell colonization within the implants in the bone defect site, the osseointegration of the implant, the matrix synthesis, and the new bone mineralization. Mallory coloration was used in order to identify mineralized bone, ECM, and cell nuclei. A difference between NF and NR4 implants could be already seen at the stage of colonization and migration of osteoblasts from the site of implantation within the implants after 15 days of implantation (data not shown).
Acknowledgments The authors thank  Jean-Luc Weickert  for his help with SEM acquisition,  Hervé Gégout  for histology, and  Leandro Jacomine  and  Christian Gauthier  for the nanoindentation experiments and analysis. This work was supported by the project  NeoTissage and NanoOSCAR  from the  Agence Nationale de la Recherche (ANR). NB-J is indebted to  CHU de Nancy, Hôpital Central, Chirurgie Orthopédique et Traumatologie (Contrat d'interface INSERM  vers l'hôpital).
A protein sequence alignment is provided in Fig  2A , a sequence identity matrix in Fig 2B. Pectate lyase allergens are classified as polysaccharide lyases, a class of enzymes which cleave galacturonic acid-containing polysaccharide chains. In general, polysaccharide lyases are divided into 23 families, at which allergenic pectate lyases are clustered in family 1 (PL1). PL1 enzymes can be found in all kingdoms; however, most lyases are of microbial origin (www. cazy. org). In higher plants pectate lyases are involved in fruit ripening  [13] [14] [15] , whereas in pollen they may play a role in tissue remodeling and in pollen tube outgrowth  [16, 17]. So far allergenic pectate lyases have been identified and acknowledged in the pollen of 11 plant species and 2 fungi (www. allergome. org; 9 are listed in the IUIS allergen nomenclature database www.
Purification and physico-chemical characterization of natural pectate lyase allergens Five clinically relevant allergenic pectate lyases (ragweed Amb a 1, mugwort Art v 6, cypress Cup a 1, mountain cedar Jun a 1, and Japanese cedar Cry j 1) were purified from aqueous pollen extracts. Homogeneity of each preparation was verified by SDS-PAGE (Fig 2C ), protein concentration was determined by amino acid analysis and protein identity was confirmed by mass spectrometry (MS). Protein preparations digested with trypsin were used for peptide mapping and peptide assignments were performed based on published allergen sequences. For Amb a 1, isoform specific peptides were found for all 5 isoforms listed in the IUIS allergen nomenclature database. The sequence coverage for Amb a 1. 01 was 68. 43%, for Amb a 1.
02 31. 66%, for Amb a 1. 03 44. 84%, for Amb a 1. 04 18. 88%, and for Amb a 1. 05 64. 99%. We found that natural Amb a 1 was composed of 47. 0% Amb a 1. 01, 7. 4% Amb a 1. 02, 11. 5% Amb a 1. 3, 22. 6% Amb a 1. 04, and 11. 5% Amb a 1. 05, respectively. The corresponding sequence identity matrix in is provided in Fig 2B. For Art v 6. 01 the sequence coverage was 40. 65%, for Cup a 1. 01 48. 27%, for Jun a 1. 01 48. 77%, and for Cry j 1. 01 43. 26%, respectively. Cry j 1 formed a double-band in gel electrophoresis, most likely as a result of heterogeneous glycosylation  [23]. Both bands were identified as Cry j 1 by mass spectrometry after tryptic digest, as well as immunoblot analysis. The immunoblot experiment was performed with an in-house produced murine monoclonal anti-Cry j 1 antibody (data not shown).
Patients´sensitization profiles were analyzed by inhibition ELISA For inhibition ELISA, sera were pre-incubated with each of the five pectate lyase allergens Amb a 1, Art v 6, Cup a 1, Jun a 1, and Cry j 1, respectively. Thereafter, IgE binding of the pre-incubated sera was tested using the allergens, which were found to be the strongest IgE binders in a distinct cohort as determined by direct ELISA experiments (Fig  4 ). In brief, Canadian and Austrian sera were tested with coated Amb a 1 and Art v 6, Italian and Japanese sera with the three Cupressaceae allergens Cup a 1, Jun a 1, and Cry j 1, respectively. All data are provided as median inhibition values. For the Austrian patients we found that Amb a 1 inhibited IgE binding to coated Amb a 1 by 96. 2%, whereas Art v 6 inhibited IgE binding by 18.
RESULTS AND DISCUSSION The Genetic Structure of West Eurasia Previous analyses of population structure have shown that despite high genetic similarity, European genetic structure is clinal and therefore heavily influenced by geography  [12, 13]. But Eurasian populations are also genetically heterogeneous; in some countries (e. g. , Sardinia) multiple genetic clusters of individuals can be inferred from genetic data, whereas in others (e. g. , Basques), individuals are more similar  [14]. To gain insight into the historical processes behind population genetic patterns in West Eurasia, we compiled a dataset of 1,235 phased West Eurasian genomes from 63 populations combined with 957 individuals from an additional 87 worldwide populations (Table  S1 )  [11, [15] [16] [17]. We accounted for potential substructure within groups with the same geographic population label by performing an analysis of population structure using the fineSTRUCTURE  [14]  genetic clustering algorithm, which identifies groups of individuals who are statistically indistinguishable from each other from a genetic point of view (Figure  1  and Supplemental Information).
(B) The fineSTRUCTURE tree of the dataset showing the clusters used in the analysis. Cluster labels contain an alphabetical prefix relating to the geographical population label of the majority of individuals within a cluster. The numerical suffix describes the total number of individuals within a cluster. A full description of the identity of the individuals in each cluster is shown in Table  S3. (C) Principal-component analysis (PCA) of the chunkcounts coancestry matrix used in fineSTRUCTURE. Each point is an individual and is labeled according to the fineSTRUCTURE cluster that it groups into as in (B). the Caucasus, Turkey, and Iran, and some individuals from Tajikistan and Turkmenistan. Similarly, we defined 18 World Regions containing sets of related clusters within different broad geographic regions of the world.
We caution that we are unlikely to have included individuals from all potential genetic donor groups to the current West Eurasian gene pool, and therefore, the gene flow events that we present should be viewed in the context of the dataset that we have used. Future work providing a better understanding of the phenotypic effects of World Region ancestry on contemporary populations as well as placing this work within the context of ancient DNA samples will further aid our understanding of Eurasian prehistory and disease. Nonetheless, the current analysis demonstrates that admixture has left a record in the genomes of all contemporary West Eurasians.
EXPERIMENTAL PROCEDURES Dataset Our dataset included 40 newly genotyped individuals (20 each from Croatia and Daghestan) together with published data, choosing samples on the basis of shared genotyping platform (Illumina 550, 610, 660W) and relevance to the peopling of Western Eurasia  [11, [15] [16] [17] 31]  (Figure  1 ; Table  S1 ). All datasets and genetic maps were based on build 36 of the human genome. We merged the datasets using PLINK (v. 1. 07) [32] , and individuals and SNPs with call rates of less than 98% were dropped. Further quality control to remove cryptically related individuals based on identity by descent (IBD) and PCA was also performed. The final dataset contained 2,192 individuals from 144 populations typed on 477,812 SNPs (Table  S1 ), which were computationally phased together using SHAPEITv1  [33].
ACKNOWLEDGMENTS We thank all anonymous donors of DNA. Additionally, we thank the staff of the  UnitaOperativa Complessa di Medicina Trasfusionale, Azienda Ospedaliera Umberto I, Siracusa, Italy. We are grateful to the  John Fell Fund at the University of Oxford  (C. C. ), the  Wellcome Trust  (S. M. , grant  098387/Z/12/Z ), the  Wellcome Trust and Royal Society  (G. H. , grant  098386/Z/12/Z ), the  Biotechnology and Biological Sciences Research Council  (G. B. J. B. ), and the  British Academy (C. C. , grant  BARDA-47870 ) for funding. Request for access to the Daghestan data should be directed to K. B. at kbulayeva@hotmail. com. J. F. W. is a shareholder, employee, and director of the commercial genetic ancestry testing company ScotlandsDNA.
7 s À 1 (Fig. 3b ). After correction for the photobleaching rate (B0. 34 s À 1 in our imaging conditions, Fig. 3b   Besides the rapid nonspecific dissociation processes, we also noted the occurrence of less frequent but longer nonspecific binding events with duration often exceeding several seconds (Fig. 3a , bottom panel). Yet with continuous imaging, estimating their duration was delicate due to the difficulty of discriminating between dissociation and photobleaching. We thus recorded time-lapse movies in which 5 ms exposure time images were interspersed with dark periods of duration t TL equal to 0. 1, 0. 5 or 1 s. In time-lapse movies, TetR proteins were considered bound when they did not move by more than 1 pixel (160 nm) over at least two consecutive images. For each data set, we computed the survival probability (SP): SPðtÞ ¼ R 1 t PðtÞdt, that is, the probability to stay bound for a time longer than t (namely the complementary cumulative probability).
1 kW cm À 2. Single-molecule trajectories were generated with the MatLab (MatLab 7. 0, Mathworks Inc. , USA) script SLIMfast, which implements the Multiple-Target-Tracing algorithm  59  and analysed using the script evalSPT. Data analysis routines are available on request. The localization precision achieved in the experiments was on the order of 25 nm and the longest traces recorded ranged up to few seconds (B1,000 frames). In our experimental conditions, the measured ensemble bleaching decay time constant for TetR-Atto647N was (2. 9±0. 7) s or (580±140) frames (mean±s. d. , N ¼ 5 cells). We calculated the MSD for each trajectory longer than eight frames and obtained the instantaneous diffusion coefficients D Inst by unconstrained linear fit of the MSD curves between time lag 2 and 5 (ref.
Acknowledgements We thank  Pierre Desbiolles  and the late  Professor Wolfgang Hillen  for their help at the initial stage of the project. We are grateful to the members of the  Transcription Imaging Consortium  and  Leonid Mirny  for many valuable discussions and to  Carl Wu , Timothee Lionnet and  Taekjip Ha  for critical reading of the manuscript. We also thank  John Macklin  for help with FCS experiments,  Andrew Belmont  for the NLS-LacI-GFP-VP16 construct,  Helen White  for cell culturing at  Janelia Research Campus ,  Ignacio Izeddin  for assistance with 3D adaptive-optics super-resolution microscopy and LacI FRAP experiments, Vincent Recamier for sptPALM data analysis,  Florian Mueller  for codes and advice on FRAP analysis, and  Marco Fondi  for help with bioinformatics analysis. We received financial support from the  Transcription Imaging Consortium at Janelia Research Campus  and from the grants  PCV DYNAFT (08-PCVI-0013 ) and TRIDIMIC from  Agence Nationale pour la Recherche (ANR).
D. N. acknowledges  Fondation Pierre-Gilles de Gennes (FPGG)  and  Fondation pour la Recherche Medicale (FRM)  for financial support. M. D. is supported by  Paris-Science- Lettres  (programme  ANR-10-IDEX-0001-02 PSL , from  Agence Nationale pour la Recherche)  and by  France-BioImaging  infrastructure (sustained by  Agence Nationale pour la Recherche ,  ANR-10-INSB-04  'Investments for the future').
These data confirm our earlier reports based on overexpressing and single-deletion or double-deletion derivatives  (4, 6, 9)  and are in good agreement with those obtained by others  (11, (21) (22) (23)  except for meropenem-AdeIJK in a single study  (11). That discrepancy could have resulted from the study of an MDR strain producing a carbapenemase  (11)  masking the moderate effect of efflux on carbapenems. No overexpression of ampC or OXA-51 was detected in strain BM4666[madeIJK]. RT-qPCR experiments were carried out to determine if the expression of intrinsic ampC and bla OXA-51-like genes was altered by the upregulation of the various efflux systems. No overexpression of ampC or of bla OXA-51-like was detected in the BM4666[madeIJK] and BM4690[madeFGH] strains. There was a significant 2-fold-lower level of production of both ␤-lactamases in strain BM4689  [madeABC].
Of note, deletion mutant BM4719[⌬adeJ] had increased susceptibility to several antibiotic classes, ␤-lactams, quinolones, tetracyclines, MLS, phenicols, antifolates, fusidic acid, and the biocide triclosan (Table  2 ), consistent with constitutive production of AdeIJK and with a major contribution of that pump to the broad intrinsic resistance of A. baumannii. E. coli-A. baumannii shuttle plasmid pCM88 confers resistance to carbapenems by production of ␤-lactamase OXA-23 and to gentamicin by production of an AAC(3)-I (unpublished data). This plasmid was electrotransformed into BM4587 and its derivatives overexpressing the three efflux systems, and the MICs of antibiotics for the transformants were determined (see Ta-ble S4 in the supplemental material). There was no consequence of overexpression of the AdeFGH and AdeIJK pumps with respect to the levels of resistance of the host strains (data not shown).
In contrast, the MICs of the carbapenems were 2-fold to 4-fold more elevated against strain BM4689[madeABC]/pCM88, and the gentamicin MICs against that strain increased from 2,048 g/ml to more than 4,096 g/ml. Since AdeABC is the only system that can extrude the carbapenems and the aminoglycosides, these data in- b Microdilution MICs of colistin were determined according to the CLSI guidelines with the addition of Tween 80 at a final concentration of 0. 002%. dicate an effect that is synergistic between efflux and other resistance mechanisms. Overexpression of adeABC and adeIJK alters bacterial membrane composition. The proteomic analysis was performed on cell envelope proteins and membrane or membrane-associated proteins from both inner and outer membranes, obtained from 4-h bacterial cultures as previously described  (28).
Annotation and comparative genome analysis. CDSs were first predicted using AMIGene (Annotation of Microbial Genomes) software  (57). Each CDS was then submitted to automatic functional annotation, and, as a final step, manual validation of automatic annotations was performed using the Mage web interface as previously described  (15). DNA manipulations and recombinant DNA techniques. A. baumannii genomic DNA was extracted using a Wizard genomic DNA purification kit (Promega). DNA amplification was performed in a GeneAmp 9700 PCR system (PerkinElmer Cetus) with Phusion High-Fidelity DNA polymerase (Thermo Scientific), and the PCR products were cloned in pCR-Blunt vector with E. coli NEB5␣ as the host strain. Nucleotide sequencing was carried out with a ceq 8000 DNA analysis system automatic sequencer (Beckman Instruments).
For each strain, three independent extractions of membrane proteins were performed and two technical replicates of each extract were analyzed. For protein quantification and identification, we used Progenesis LC-MS software (Nonlinear Dynamics), retaining the same statistical parameters as previously described for peptides  (42). The merged peak list was searched against the A. baumannii AYE database (http://www. ncbi. nlm. nih. gov/protein) using a local version of Mascot (version 2. 2; Matrix Science). Protein fold change was taken into account when the value was above 2. At least 3 peptides were used for protein identification and quantification. Biofilm assays. Biofilm formation by A. baumannii BM4587 and its derivatives was examined either on pegs using a Calgary device (Innovotech, Edmonton, Canada) for solid-support biofilms  (42)  or in 24-well plates for formation of biofilms together with pellicles  (42).
Biofilm biomass was quantified after 48 h of growth at 37°C by crystal violet staining as previously described  (42). Assays were performed in triplicate at least, and data are expressed as means Ϯ standard errors of the means (SE). Results were analyzed using Prism Graph Pad 5 software by a one-way analysis of variance (ANOVA) method to assess significant differences of biofilm growth between the strains. Motility and transformation. Motility and transformation experiments were carried out as previously described  (36). For both tests, plates were composed of 0. 5% agarose, 5 g/liter tryptone, and 2. 5 g/liter NaCl. The inoculum was stabbed into the semisolid medium to enable growth at the surface and at the interface between the agar and the bottom of the petri dish, and the plates were sealed with Parafilm to prevent drying.
For the standard filter method, A. baumannii BM2580 harboring self-transferable plasmid pIP1841 (39) was used as a donor. Equal amounts of donor and recipient overnight cultures in LB were harvested, washed with an equal volume of LB, and mixed on a mating filter (Millipore) placed on LB agar. After 5 h of mating at 37°C, cells were recovered and plated on LB agar with antibiotics selective for donors (kanamycin at 50 g/ml), recipients (rifampin at 50 g/ml), and transconjugants (kanamycin at 50 g/ml and rifampin at 50 g/ml). The frequency was calculated as the number of transconjugants per donor. Nucleotide sequence accession number. The assembled sequence of A. baumannii BM4587 was submitted to the GenBank database and is accessible under accession number JNOT00000000.
ACKNOWLEDGMENTS We thank  C. Bouchier  for whole-genome sequencing,  G. Wilharm  for the gift of A. baumannii 179 DNA,  V. Barbe  for optical genome mapping and helpful discussions, and the platform Genotyping of  Pathogens and Public Health, Institut Pasteur , for coding multilocus sequence type (MLST) alleles and profiles available at http://www. pasteur. fr/mlst. E. -J. Y. was supported by an unrestricted grant from  Reckitt-Benckiser.
Observed (001) peaks of Mo 1-x W x Se 2 appear at the same position (within < 0. 08 • ) implying that alloys have similar c-axis parameters. Consistent with nano-XPS measurements, Rutherford backscattering spectroscopy (RBS) data collected from ∼ 100 µm diameter circle agrees well with the XPS measurements (not shown). Optical Spectroscopy. -Experiments at T = 4 -300 K are carried out in a confocal microscope  [8]. The detection spot diameter is ≈ 1µm, i. e. considerably smaller than the monolayer flake size of ∼ 10 µm×10 µm. For time integrated experiments, the PL emission is dispersed in a spectrometer and detected with a Si-CCD camera. The samples are excited either by a cw He-Ne laser or ps pulses generated by a tunable frequency-doubled optical parametric oscillator (OPO) synchronously pumped by a mode-locked Ti:Sa laser.
Acknowledgements We acknowledge funding from  ERC  Grant No. 306719 ,  ANR MoS2ValleyControl. I. C. G. acknowledges the  CNRS  for financial support and  CALMIP initiative  for the generous allocation of computational times, through the project  p0812 , as well as the  GENCI-CINES  and  GENCI-IDRIS  for the grant x2015096649. S. T acknowledges  Arizona State University  start-up grant and  Ira. A. Fulton College of Engineering Origami Seeding Funds.
Quantitative Evaluation Readers 1, 2, and 3 recorded lesion SI measurements relative to normal brain parenchyma for 63, 66, and 54 lesions (Arm 1) and 84, 89, and 78 lesions (Arm 2), respectively, on T1SE images and for 60, 61, and 51 lesions (Arm 1) and 82, 85, and 75 lesions (Arm 2), respectively, on T1GRE images. No lesions below 5 mm were measured by any of the readers. Analysis of quantitative SI data revealed no carryover effects across readers for any assessment (P Ͼ. 05). The mean percentage signal enhancement of lesions on T1SE images was significantly (P Յ. 0006) higher for gadobenate compared with gadoterate for all 3 readers in patients given 0. 1mmol/kg doses of both agents (Arm 1), while no meaningful differences were noted between 0. 05-mmol/kg gadobenate and 0. 1mmol/kg gadoterate (Arm 2) (Fig  3A ).
Simulations We have implemented a program generating pseudo-data to compare the predictions with. This program simulates over generations the aforementioned population model. Here, a segment is modeled not as a set of nucleotides but as a continuous object, and hence the program records on the one hand the starting and ending edges of each block and on the other hand the origin of this block, which is the label of the founder segment this block belonged to. With this program, we have simulated 10000 replicates over 3000 generations, with 10 different population sizes (from 10 to 100 individuals) and with a segment length ranging from 1 to 5 Morgan. The program has been implemented in C++ (version C++11, compiled with g++ 4. 9. 2), and graphical outputs have been obtained with R (version 3.
Genome sequencing was performed by combining a 454 pyrosequencing method and PacBio SMRT technology to provide both high coverage and high-quality contigs  (12). The 454 reads (191,539 reads) have been converted to the FastQ format using the seq_crumbs package (version 0. 1. 8; http://bioinf. comav. upv. es/seq_crumbs/) and trimmed using StreamingTrim (version 1. 0)  (13). Both 454 and PacBio reads quality has been checked using FastQC (version 0. 10. 1) (http://www. bioinformatics. babraham. ac. uk/projects/fastqc/). The PacBio reads (118,344 reads) coverage was found to be high enough to perform a hybrid assembly (~80ϫ), using the pacBioToCA and the runCA program of the Celera assembler  (12). The best assembly parameters have been checked using the Quast Web server  (14). The draft genome comprises 97 contigs.
The total length is 5,094,121 bp, containing 4,365 protein-coding sequences (CDS) and 129 RNA-coding sequences detected after automatic annotation using prokka (version 1. 7. 2)  (15). Among these, 88 tRNA sequences and 40 rRNA were found, corresponding to about 13 rRNA clusters. However, the number of rRNA clusters may be inferior, due to the draft status of the IFB0099 genome. The GC content is 56. 4%. Pathogenicity-related genes, for example those coding for pectate lyases and cellulases, were annotated. A high level of homology was found with the best-characterized strain of the Dickeya genus, Dickeya dadantii 3937  (16). Nucleotide sequence accession numbers. The draft genome sequence of D. solanii IFB0099 has been deposited in GenBank under the accession no. JXRS00000000. The version described in this paper is the first version, JXRS01000000.
ACKNOWLEDGMENTS This work was supported by a cooperative project between Poland and France ( NSC 2013/08/M/NZ9/00974  to E. L. ) and a collaborative project between  Poland and Italy  ( Canaletto Program  code  PL13MO1/MNiSW-WWM-183-782-Z/MBA/10  to M. B. and E. L. ). We are grateful to the  DTAMB platform and Biofidal  (http://dtamb. univ-lyon1. fr/) for the 454 genome data.
A high-resolution transmission electron microscopy (HRTEM) image for a grain in composition X0 is shown in Fig. 4. The electron diffraction pattern for the grain is shown as an inset in the bottom-right corner of the image. The electron diffraction pattern can be indexed as a [001] diffraction pattern for Ba 6À3x Nd 8+2x Ti 18 O 54 tungsten bronze, 10 confirming the stability of the ceramic after annealing in the reduced atmosphere. Similar TEM data were obtained for compositions X27 and X85. An atomically resolved [001] high-angle annular dark-field (HAADF) image for a grain in sample X0 annealed at 1400°C for 12 h is shown in Fig. 5a. The Z-contrast image provides direct atomic evidence of the structural model  10       shaped rows containing seven atomic columns in each row. The pentagonal tunnels are at end of each row, and five tetragonal tunnels are in between the pentagonal tunnels.