dataesr/scientific-paragraphs-categorization huggingface dataset:
001 to 0. 3 Å À1 , by using three sample-detector distances. The high flux available from the reactor source enabled measuring times of 30 minutes or less for each instrument setting. The data were reduced to 1D scattering curves of intensity vs. Q using the facility provided software. This involves the following key steps: the electronic background is subtracted; the full detector images for all data are normalised; scattering from the empty cell is subtracted and finally the data are radially averaged to produce the 1D curves for each detector position. The absolute scaling of the middle detector position data, taken under optimum conditions, is then used as the reference point for the other two data sets as they are scaled to form a single curve. The scattering from D 2 O (the solvent) was also measured and subtracted from the data as discussed alongside the results.
The instrument-independent data were then fitted to customised models in the SasView software package, 56 these combined an absolute power law with either a hollow cylinder  57  or a (Kratky-Porod) flexible cylinder. 58, 59 The Q-dependent power law (Q ÀN ) accounts for the mass fractal contribution to the scattering intensity, which is superimposed on that from the cylindrical structures i. e. the micelles or fibrils. While the worm-like micelles are represented by hollow cylindrical rods, the fibrils of the gel are represented as a solid flexible wormlike chain of cylindrical Kuhn segments within the flexible cylinder version of the model.
Acknowledgements AZC thanks the  University of Liverpool  for funding. DA thanks the  EPSRC for a Fellowship  ( EP/L021978/1 ). The experiment at the  Institut Laue Langevin  was allocated beam time under experiment number  9-10-1304. This work benefitted from the SasView software, originally developed by the  DANSE  project under  NSF  award  DMR-0520547.
Rheological Studies The mechanical properties of hydrogels stabilized by bolaamphiphile 7 were characterized by rheological measurements. The storage (G ) and loss (G ) moduli provided information about the visco-elastic properties of gels. The frequency dependence of G and G moduli for the hydrogel stabilized by compound 7 (4% w/v) indicates that G exceeded G below a strain of 0. 5% and an angular frequency 1 Hz (data not shown). The hydrogel stabilized by 7 exhibits a dominant elastic character (solid-like) as expected for a supramolecular network. The G value is 57 kPa at an angular frequency of 1 rad/s for the hydrogel at 4% w/v. Importantly, compared with the ether analogue (Figure  1a ), which possesses a G value is 30 kPa in similar rheological conditions, the elastic character of the hydrogel improved with the bolaamphiphile 7.
Rheological Studies The mechanical properties of hydrogels stabilized by bolaamphiphile 7 were characterized by rheological measurements. The storage (G′) and loss (G′′) moduli provided information about the visco-elastic properties of gels. The frequency dependence of G′ and G′′ moduli for the hydrogel stabilized by compound 7 (4% w/v) indicates that G′ exceeded G′′ below a strain of 0. 5% and an angular frequency 1 Hz (data not shown). The hydrogel stabilized by 7 exhibits a dominant elastic character (solid-like) as expected for a supramolecular network. The G′ value is 57 kPa at an angular frequency of 1 rad/s for the hydrogel at 4% w/v. Importantly, compared with the ether analogue (Figure  1a ), which possesses a G′ value is 30 kPa in similar rheological conditions, the elastic character of the hydrogel improved with the bolaamphiphile 7.
22 g, 20 mmol) in anhydrous DMF (100 mL). After stirring for 24 h at 65 • C, the mixture was cooled to room temperature and poured into water (200 mL). The resulting solid was filtered off, washed with water, and dried under vacuum, with a crude yield of 6. 92 g (92%). NMR data were identical with those obtained from a commercial sample of the product. N-3-[1-((β-D-Glucopyranosidetetraacetate)-1H-1,2,3-triazol-4-yl)methyl]thymidine (3) Copper sulfate (0. 260 g, 1. 63 mmol) and sodium ascorbate (0. 645 g, 3. 26 mmol) were successively added to a degassed suspension of (1) (4. 59 g, 16. 3 mmol) and 1-deoxy-1-azido-2,3,4,6-tetra-O-acetyl glucopyranose (2) (6. 085 g, 13. 3 mmol) in 100 mL of t BuOH/H 2 O (1:1). The mixture was stirred at 75 • C for 7 h. After cooling to room temperature, the solvents were removed under reduced pressure.
Acknowledgements This work was conducted in the framework of the  IFREMER internal R&D  project '' PJ0807 -Acoustique Sous-Marine ''. The publication of this work was suggested and encouraged by  Pr. Larry Mayer  ( UNH/CCOM, Durham, NH ), who brought many improvements to the manuscript. The measured directivity pattern of EM 300 transducer is published here by courtesy of  Kongsberg Maritime , thanks to  Berit Horvei. The author acknowledges the support of his IFREMER colleagues involved in our common activity in sonar performance modelling and measurements.
Real-time quantitative PCR. Real-time quantitative PCR reactions were performed as previously described  39  (Supplementary Methods). Immunoblot analysis. Protein samples were dissolved in SDS sample buffer (Laemmli), heated to 96 °C for 5 min, and loaded onto a 4-15% Criterion TGX Stain-Free Precast gel (Bio-Rad). The gel-separated proteins were imaged with the Gel-Doc EZ system (Bio-Rad), directly transferred onto polyvinylidene difluoride membrane and probed with various antibodies (Supplementary Methods). Scans were acquired with the Odyssey Fc system (Li-Cor), and analysed using Image Studio 2. 0 software (Li-Cor). Immunoblot band intensities were normalized to the total amount of protein loaded, as quantified using Image Lab 3. 0 software (Bio-Rad). Subcellular fractionation. Subcellular fractions were prepared as described previously  19  , with some modifications (Supplementary Methods).
The experimenter was blind to the construct used, which was revealed after analysis. For endogenous GluA2 QD tracking, rat hippocampal neurons were incubated with monoclonal antibody directed against N-terminal extracellular domain of GluA2 subunit for 10 min followed by 5-min incubation with QDs 655 Goat F(ab')2 anti-mouse IgG (Invitrogen). QDs were detected by using a mercury lamp and appropriate excitation/emission filters. Images were obtained with an interval of 50 ms and up to 1,000 consecutive frames. Signals were detected using a CCD (charge-coupled device) camera (Quantem; Roper Scientific). QD recording sessions were processed with the Metamorph software (Universal Imaging Corp. ). The instantaneous diffusion coefficient D was calculated for each trajectory, from linear fits of the first four points of the mean square displacement versus time function using MSD(t) ¼ or 2 4 (t) ¼ 4Dt.
The two-dimensional trajectories of single molecules in the plane of focus were constructed by correlation analysis between consecutive images using a Vogel algorithm. QD-based trajectories were considered synaptic if co-localized with Homer 1C dendritic clusters for at least five frames. Fluorescence lifetime imaging microscopy experiments. The experimenter was blind to the construct used, which was revealed after analysis. FLIM experiments were performed at 37 °C using an incubator box with an air heater system (Life Imaging Services) installed on an inverted Leica DMI6000B (Leica Microsystem) spinning disk microscope and using the LIFA frequency domain lifetime attachment (Lambert Instruments) and LI-FLIM software. Cells were imaged with a HCX PL Apo Â 100 oil numerical aperture (NA) 1.
4 objective using an appropriate green fluorescent (GFP) filter set. Cells were excited using a sinusoidally modulated 1-W 477-nm LED (light-emitting diode) at 40 MHz under wild-field illumination. Emission was collected using an intensified CCD LI2CAM camera (FAICM, Lambert Instruments). The phase and modulation were determined from a set of 12 phase settings using the manufacturer's software LI-FLIM software. Lifetimes were referenced to a 1-mM solution of fluorescein in saline (pH 10) that was set at 4. 00 ns lifetime. Following FLIM measurements, cells were excited using a 100-mW 491-nm DPSS laser (Calypso, Cobolt) for GFP imaging and a 100-mW 561-nm DPSS lasers (Jive, Cobolt) for imaging, and imaged with a HCX PL Apo CS Â 63 oil NA 1. 4 objective. Signals were recorded with a back-illuminated Evolve EMCCD camera (Photometrics).
Moderate stimulation intensity was assessed during an I/O protocol at the beginning of each recording. Synaptic changes were recorded in response to 10 pulse presynaptic stimulation at frequencies between 2 and 50 Hz at a holding potential of -70 mV. Slices were superfused with standard 32-°C aCSF, which was supplemented with 10 mM SR-95531 (Gabazine). NMDA currents were measured as indicated above in the additional presence of 2 mM NBQX voltage clamped at -30 mV. NMDA receptors were blocked by the addition of 20 mM APV to visualize the nature of the remaining current. Statistics. Data are presented as mean±s. e. m. or medians±IQR defined as the interval between 25 and 75% percentile. All tests were two-sided. Replicates were biological in nature. Cell imaging. Normally distributed data sets were compared using the paired Student's test and unpaired Student's t-test.
Statistical significance (Prism 4. 0 (GraphPad)) between more than two normally distributed data sets was tested by one-way analysis of variance test followed by a Newman-Keuls test to compare individual pairs of data. Non-Gaussian data sets were tested by non-parametric Mann-Whitney test. Electrophysiology. Data were analysed using custom-made Matlab (Mathworks) software and MiniAnalysis (Synaptosoft) for the analysis of mEPSCs. Rise times were measured as the time that it took to get from 20 to 80% of the maximal amplitude. Current decays are reported as decay time (90-10%) when stated, otherwise the desensitization time constant that was determined by fitting double exponential curves, is reported. Statistical significance was assessed using Graphpad Prism 5 software (GraphPad Software).
Acknowledgements We thank  Joost Hoetjes  and  Robert Zalm  for genotyping;  Frank Koopmans  for proteomics support; the  Bordeaux Imaging Center , part of the  FranceBioImaging national infrastructure , for support in microscopy; the IINS cell biology core facility for providing neuronal cultures; and the Pole in vivo for mice breeding in Bordeaux. A. B. S. , H. D. M. and S. S. received support from  HEALTH-2009-2. 1. 2-1EU-FP7  ' SynSys ' (# 242167 ). R. V. K. was funded by  NWO-ALW  grant (# ALW2PJ/12048 ), J. S. was funded by  EU Marie Curie ITN CerebNet  ( MEST-ITN-2008-238686 ). A. B. S. , H. D. M. and L. J. M. S. were funded by the  Dutch Neuro-Bsik Mouse Pharma Phenomics consortium  (grant  BSIK 03053  from  SenterNovem ) and P. R. R. was funded by  EU Marie Curie ITN 'Neuromics'  ( MEST-CT-2005-020919 ).
S. S. was supported by an  NWO   VICI grant  ( ALW-Vici 016. 150. 673 ). H. D. M. was supported by an  NWO   VICI grant  ( ALW-Vici 865. 13. 002 ) and the  ERC grant BrainSignals  ( 281443 ). D. C. , A. S. H. , F. C. , J. P. and C. R. were supported by funding from the  Ministere de l'Enseignement Superieur et de la Recherche ,  Centre National de la Recherche Scientifique , the  Conseil Regional d'Aquitaine  and the  ERC  grant nano-dyn-syn to DC.
Fungal DNA was extracted using a hydraulic press (Carver, Inc. , Wabash, USA) to lyse the cell walls and the Genomic-Tip 100/G kit (Qiagen 1 , CA, USA) following the manufacturer's protocol. DNA purity was assessed by measuring 260/280 and 260/230 absorbance ratios with a NanoDrop 1 spectrophotometer (2000; Thermo Scientific, Wilmington, USA), and DNA concentration was measured using a Qubit 1 fluorometer (2. 0; Thermo Scientific). Preparation of DNA libraries was performed by the GeT-Place INRA platform, Toulouse, France. Mate-pair libraries with insert sizes of 3kb were prepared with Illumina Nextera TM Mate Pair Sample Prep kits, and sequencing was performed on a HiSeq 2000 Illumina TM sequencer at a depth of coverage of 100X on average. The genome sequence of M. saponariae is available in GenBank under the accession number PRJEB11435.
PCR Multiplex Assembling For the assignment of PCR multiplexes we defined four amplification size ranges: 1) 100 to 115 bp; 2) 125 to 150 bp; 3) 155 to 170 bp; and 4) 180 to 210 bp. These groups were defined to separate the microsatellite markers by size and thus avoid interference between markers within each multiplex. For each multiplex, compatibility of the primer pairs for each locus was tested with the software Multiplex Manager (1. 2;  [39] ). As only four different colours of dye are available we set the maximum number of loci per reaction to four and a complementary threshold equal to seven (default parameter). Primer pairs were then successfully combined into six multiplexes, ranging from three to four markers per multiplex (Table  1 ).
PCR reactions were performed separately for each multiplex in 12,5 μL volume containing 3 μL of DNA, ¼ of the recommended volume of multiplex PCR Kit (Qiagen 1 , USA), and 1. 25 μL of the primer mix. The primer mix included 2 μM of unlabelled forward and reverse primer and 0. 5 μM or 0. 75 μM of labelled forward primer depending on the dye label. FAM and Yakima Yellow dyes were at 0. 75 μM, while ATTO 550 and ATTO 565 dyes were at 0. 5 uM. The PCR cycling program used was the same as described above. After checking for successful PCR amplifications on 2% (w/v) agarose gel electrophoresis, PCR amplicons were diluted and fractionated by capillary electrophoresis at the GENTYANE INRA platform as previously described. Alleles of each locus were scored using GENEMAPPER 5. 0 (Applied Biosystems TM , USA).
Bacterial community analysis Microbial diversity was investigated on a Sterivex TM filter previously stored at À20°C. The filter was crushed in liquid nitrogen and the DNA extracted with the Powersoil DNA Isolation kit (MoBio Laboratories, Inc. , Carlsbad, CA, USA) following the manufacturers' specifications. Genomic DNA was sent to a commercial company (MR DNA, Shallowater, TX, USA). The hypervariable V4 region of the 16S rRNA gene was amplified with PCR primers 515/ 806 and sequenced by the MiSeq 2 9 300 bp run (Illumina, San Diego, CA, USA). The construction of DNA libraries with the amplicons and the sequencing were performed following the manufacturers' specifications. The sequence data were subsequently processed through the analysis pipeline designed by MR DNA. At first, the sequences were demultiplexed and the barcodes and primers were removed before eliminating all sequences smaller than 150 bp.
Sequences displaying ambiguous bases were also eliminated. Operational taxonomic units (OTUs) were defined by clustering sequences displaying 97% similarity. Thus, singleton sequences and chimeras were eliminated. The final OTUs were subsequently classified taxonomically using BLASTn against a curated database derived from RDPII and NCBI. Cloning and sequencing of benzylsuccinate synthase alpha-subunit (bssA) genes PCR amplifications of the bssA gene were performed for different sets of primers found in the literature. The primer sets 7772F/8546R  (Winderl et al. , 2007) , 7768F/8543R  (von Netzer et al. , 2013) , bss3F/bssAR  (Staats et al. , 2011) , and 997F/1230R  (Brow et al. , 2013)  were used to target, respectively, the bssA gene of Deltaproteobacteria, Clostridia, Geobacter and nitrate-reducing Betaproteobacteria (Table  S1 ).
Capture probe design and synthesis A set of five 31-to 38-mers degenerate probes covering the bssA gene was designed from nine bssA nucleic sequences from strains belonging to Deltaproteobacteria, Firmicutes (EF123665, EF123667, EU780921, FO203503, EF123663, EF123662) and environmental sequences obtained with 7772F/8546R primers set. These three latter amplicons were obtained at the end of TX degradation from enrichment cultures with autochthonous microbiota of different deep aquifers (aquifer 1: KX576576, aquifer 2: KX576577, aquifer 3: KX576575). The deep aquifer 2 was studied by  Berlendis et al. (2010)  (Paris Basin). The third aquifer (aquifer 3) is located in the Aquitaine Basin (southwest of France). These sequences were processed using the KASpOD software  (Parisot et al. , 2012)  (Table  S1 ).
Illumina MiSeq sequencing and data analysis Captured DNA products were sequenced using a single MiSeq 2 9 300 bp run (Illumina) according to the manufacturer's specifications (Genoscreen). All raw reads were scanned for library adaptors and quality filtered using PRINSEQ-lite PERL script  (Schmieder and Edwards, 2011)  prior to assembly and analysis. The clean reads were assembled de novo using IDBA-UD (v1. 1. 1) (Peng et al. , 2012). Contigs generated were combined for a second round of assembly using CAP3 to generate longer contigs  (Huang and Madan, 1999). The amino acid (AA) sequences were deduced from the final assembled nucleotide contigs and then aligned with reference open-reading frames sourced from public databases using MEGA version 6  (Tamura et al. , 2013). The phylogenetic tree was constructed with the same software using the neighbour-joining method.
The SHS probes (Table  S1 ) were designed from bssA sequences of sulphate-reducing bacteria belonging to the Deltaproteobacteria and the Firmicutes, as well as the three sequences previously amplified with the primers of  Winderl et al. (2007)  in enrichments with mono-aromatic hydrocarbons (KX576575, KX576576, KX576577). After analysis of reads (Table  S2 ), 498 500 reads proved close to bssA and bssA-like genes and were grouped into three bssA homologous contigs. The contig sequence_10944 alone includes 98% of the bssA reads indicating that such bssA gene dominates in the ecosystem. Sequence capture by hybridization gives quantitative results close to that obtained by qPCR as demonstrates by  Denonfoux et al. (2013). The three contigs obtained by sequence capture and the three bssA amplicons obtained in this study were compared with sequences from pure strains and environmental samples deposited in international databases after having been translated into AA sequences.
AssA NmsA BssA Fig. 3. Phylogenetic tree based on partial bssA-like amino acid sequences from deep aquifers used for geological natural gas storage (in bold; this study) compared with sequences from pure strains, enrichment cultures or environments retrieved in the databases. Sequences in bold were obtained by PCR from genomic DNA from mono-aromatic hydrocarbon-degrading enrichment cultures (aquifers 1, 2 and 3). Sequences in bold and italic were obtained by SHS method directly from formation water (aquifer 1). The evolutionary distances were computed using the Poisson correction method. Evolutionary analyses were conducted in MEGA6 with a bootstrap test of 1000 replicates. bssA-like sequences to be obtained directly from FW. Therefore, this method constitutes a major asset in developing a clearer understanding of ecosystems and in monitoring bioattenuation phenomena in the context of mature environmental engineering.
1999)  even though linkage between sites may affect the distribution of mutations  (Williamson and Orive 2002). Mutations of mild deleterious effect are abundant in some bacteria  (Hughes 2005; Balbi et al. 2009). If bacterial evolution is dominated by these mutations then selection might not strongly affect demographic inference using skyline plots. However, recent studies have suggested that weak purifying selection, when occurring at multiple sites, could affect the shape of the coalescent tree  (O'Fallon et al. 2010). The effect of selection on skyline plots remains unclear. The possibility of producing large sequence datasets for microbial populations has spurred interest on the use of these methods to study microbial demography. The skyline plot has been particularly popular because it allows precisely detailing demographic changes  (Ho and Shapiro 2011).
This bias may also result from sampling different environments (or patients) while analyzing a single isolate per site (thus disregarding differences in population sizes in each site). Finally, a very common type of mixed sampling bias is found in studies extensively sampling a sub-population and a small number of very diverse individuals from other sub-populations. This gives a broad view of  Lapierre et al. doi:10. 1093 /molbev/msw048 MBE the genetic diversity in the species, while focusing in a subpopulation of interest. Analyses using sequences available in databanks are prone to combine the sampling biases of the different underlying studies. We surveyed the available literature on the use of skyline plots to describe bacterial population demography and found that nearly all studies showed skyline plots suggestive of population expansion.
ClonalFrame Analysis and Subsequent Skyline Plot ClonalFrame was used with default parameters on the results of ten simulations with recombination, no selection and no sampling bias. All ClonalFrame outputs were imported in the ClonalFrame GUI  (Didelot and Falush 2007). The convergence of MCMC traces was visually assessed. ClonalFrame outputs ultra-metric trees with multifurcations, but bifurcating trees are necessary to compute skyline plots. Hence, for each simulation, we exported the recombination-free distance matrix and used the R package phangorn to construct the UPGMA trees  (Schliep 2011). We computed generalized skyline plots using the skyline function of the ape package  (Paradis et al. 2004 ). The AIC criterion was applied to find the optimal spline parameter.
Acknowledgments We thank  Sylvain Brisse ,  Adam Eyre-Walker , and  Guillaume Laval  for comments on an earlier version of this manuscript. This project was financed by the  Centre National de la Recherche Scientifique (CNRS)  and the  Institut Pasteur. G. A. and M. L. acknowledge support from the grant  ANR-12-BSV7-0012  Demochips from the  Agence Nationale de la Recherche (France). M. L. is funded by the  PhD program Interfaces for Life of the University Pierre and Marie Curie (Paris). C. B. is funded by the  PhD program Complexitedu Vivant of the University Pierre and Marie Curie (Paris).
The importance of review articles in making the voice of rare diseases heard: OJRD's 10th anniversary Ségolène Aymé "Join us in making the voice of rare diseases heard" is the slogan of Rare Disease Day 2016, a special day established by EURORDIS (http://www. rarediseaseday. org/). It takes place on the last day of February each year since 2008, to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients' lives. This has also been one of the goals of Orphanet Journal of Rare Diseases (OJRD), since its inception 10 years ago. This year's slogan appeals to everyone who can make a difference but it appeals to us healthcare professionals and researchers first. We have a duty to create greater awareness for each of the thousands of rare diseases identified so far, by publishing the scarce data to which we have access.
Orphanet Journal of Rare Diseases (OJRD) is committed during this commemorative year and beyond, to publishing review articles on specific rare diseases with the goal of expanding knowledge among health professionals and caregivers. Such articles are highly valued by patients and caregivers, especially for very rare diseases. Summarising the available published literature is a major effort requiring experience, an asset of only a few professionals around the world. It is also a time-consuming exercise which is often postponed by many experts who are already overloaded. OJRD invites the rare disease community of experts to write up such reviews as the necessary step to make possible the dissemination of knowledge on diseases which are never taught at medical school. According to the Orphanet database, which systematically collects such articles provided that the copyright holders give permission to provide free access, there are currently 400 review articles published in peerreview journals, covering 1132 rare diseases.