dataesr/scientific-paragraphs-categorization huggingface dataset:
Balancing the program and community expectations needs to be carefully considered and budgeting for maintenance and support is essential. Likewise, end users need to be encouraged to provide all of the relevant metadata in a timely manner so as not to impede the JGI workflow. This is especially true with regard to metagenomic studies. 2. Support downloading of all data (i. e. JGI and non-JGI) from IMG/portals? -How important is submission of the isolate genomes and single cells to Genbank? The topic was discussed and there was a general feeling among the Advisory Committee members that Genbank submission had become a major project cost and bottleneck. If an alternative approach existed that would guarantee availability of data in a consistent manner, it might prove a better long-term option, especially if it were a distributed solution.
Concentrations of 5 0 TMR-cTAR-3 0 Fl and TAR were 10 and 100-600 nM, respectively, to ensure pseudo-first order conditions. Both reactants in identical volumes coated by NC peptides were mixed together to trigger the reaction. The apparent rate constants k obs were determined from kinetic traces, as previously described  (20). All fitting procedures were carried out with the Microcal Origin 6. 1 software based on non-linear least-squares methods, applying the Levenberg-Marquardt algorithm.
The mean lifetime hi was calculated according to hi=AE i i. The population 0 of dark species was calculated by 0 = 1 À { free / (t sample Â R m )} where t free is the lifetime of the free 2-Ap riboside, t sample is the measured lifetime of 2-Ap within the oligonucleotide (either free or bound to NCp7), and R m is the ratio of their corresponding quantum yields. The remaining amplitudes of each fluorescent population were recalculated according to c = i Â (1À o ). All fitting procedures were carried out both with the maximum entropy method Pulse5 software and a software based on an iterative application of the Marquardt's method in non-linear least-squares analysis (kindly provided by G. Krishnamoorthy).
Alignment of TAR sequences TAR sequence alignments were performed using the HIV sequence database from the Los Alamos National Lab HIV (http://www. hiv. lanl. gov/content/sequence/HIV/mainpage. html). A position-weighted matrix was then computed using the open-source statistical software R from the Comprehensive R Archive Network (http://www. Rproject. org/) (50). The sequence logo  (51)  was plotted using the seqLogo package (http://www. bioconductor. org/ packages/devel/bioc/html/seqLogo. html).
In contrast to 2-Ap35, a significantly lower QY was observed for 2-Ap28, suggesting an efficient quenching of the probe by the G 29 residue in the loop. In line with nuclear magnetic resonance (NMR) data showing that the loop of cTAR is highly flexible  (58) , fast conformational fluctuations may drive 2-Ap28 from unstacked to stacked conformations, resulting in a low QY value. Taken together, we observed a strong dependence of 2-Ap fluorescence signals on the sequence and/or the structure of the DNA segments in which the 2-Ap is inserted. The 2-Ap signals easily discriminated stable regular ds-segments from positions destabilized by bulges or mismatches and clearly showed heterogeneous 2-Ap environments along the cTAR sequence. To further characterize the local 2-Ap environment in the various labelled cTAR sequences, thermal melting curves were recorded using the 2-Ap fluorescence signal.
Conservation of the cTAR sequence and structure If G 10 and G 50 residues are critically involved in NCp7 recognition sites needed for efficient strand transfer, it is likely that these positions must be conserved. To check whether these positions corresponded to conserved motifs within the HIV subtypes, we aligned the cTAR sequence presented in Figure  1  to the LANL HIV subtype reference database (http://www. hiv. lanl. gov). The 587 sequences retrieved from the QuickAlign procedure were used to calculate a position weight matrix from which a sequence logo was derived (Figure  7 ). This sequence logo is drawn such that the overall height of the stack indicates the information content at each position (derived from the Shannon entropy), whereas the height of the base symbols within the stack indicates their relative frequency  (51, 73, 74).
Experimental Crystal data  Data collection: APEX2  (Bruker, 2006) ; cell refinement: SAINT  (Bruker, 2006) ; data reduction: SAINT; program(s) used to solve structure: SIR97  (Altomare et al. , 1999) ; program(s) used to refine structure: SHELXL97  (Sheldrick, 2008) ; molecular graphics: ORTEP-3 for Windows  (Farrugia, 1999) ; software used to prepare material for publication: WinGX publication routines  (Farrugia, 2012)  and CRYSCAL (T. Roisnel, local program).
Computing details Data collection: APEX2  (Bruker, 2006) ; cell refinement: SAINT  (Bruker, 2006) ; data reduction: SAINT  (Bruker, 2006) ; program(s) used to solve structure: SIR97  (Altomare et al. , 1999) ; program(s) used to refine structure: SHELXL97  (Sheldrick, 2008) ; molecular graphics: ORTEP-3 for Windows  (Farrugia, 1999) ; software used to prepare material for publication: WinGX publication routines  (Farrugia, 2012)  and CRYSCAL (T. Roisnel, local program).
Acknowledgments We thank our former colleague  Dr Lila Lalioui  for the construction of the NEM316 Dbsp mutant and the purification of the recombinant histidyltagged Bsp protein. We thank  Arnaud Firon  for the isolation of two Himar mutants ( NEM3694  and  NEM3695 ) in gbs0470 encoding Alp2. We thank our colleagues from the Imagopole for their invaluable help in deconvolution analyses. We thank the reviewers for their critical eye and their useful suggestions to improve this study.
This work was supported in part by grant  ANR-06-PATHO-001-01  from the  Agence Nationale de la Recherche  '' ERA-NET PathoGenoMics''  (to P. T. -C. ) and by the  Institut Pasteur. The authors also acknowledge funding from the  French Government 's  Investissement d'Avenir program ,  Laboratoire d'Excellence ''Integrative Biology of Emerging Infectious Diseases' ' (grant nuANR-10-LABX-62-IBEID). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Experimental procedures Data recording and preprocessing. We analyzed data from five subjects (3 females (aged 21, 23, and 27), two males; (aged 25 and 48)) with refractory partial epilepsy undergoing presurgical evaluation. The subjects were hospitalized between February 2005 and March 2007 in the epilepsy unit at the Pitie-Salpetriere hospital in Paris. All patients gave their informed consent and procedures were approved by the local ethical committee (CCP). Each patient was continuously recorded during several days (duration range, 9-20 days; mean duration, 16 days) with intracranial and scalp electrodes (Nicolet acquisition system, CA, US). Depth electrodes were composed of 4 to 10 cylindrical contacts 2. 3-mm long, 1-mm in diameter, 10-mm apart center-tocenter, mounted on a 1 mm wide flexible plastic probe.
Pre and post implantation MRI scans were evaluated to anatomically locate each contact along the electrode trajectory. The placement of electrodes within each patient was determined solely by clinical criteria. Signals were digitized at 400 Hz. For sleep data, two seizure-free nights with at least two complete sleep cycles were chosen from each of the subjects; in addition, for wakefulness data, between one and four seizure free recording hours were chosen preceding or following the night (for eight out of the ten nights). For each night, sleep stages were scored using the software Somnologica Studio (Embla Systems, Inc, CO, USA) and scores were visually confirmed by a time-frequency analysis. The four sleep stages were: REM, s1, s2, and s3/s4. (Sleep stages s3 and s4 were combined to s3/s4 to adapt to the AASM standards (REM, N1, N2, N3)  [61] , and s1 could not be used for the analysis because not all patients showed sufficiently long s1 sleep intervals).
These three sleep stages together with the wake state made up the four vigilance states. The five subjects were implanted with (44, 48, 50, 50, and 63) intracranial LFP recording sites. In total 7 recording sites were excluded from the analysis due to artifacts and thus we used  (44, 48, 45, 50, and 61)  recordings sites for data evaluation. All LFP were lowpass filtered at 40 Hz (4 th order butterworth, MATLAB) to reduce the impact of line noise. Event definition for avalanches. Neuronal avalanches are spatiotemporal clusters of events which are separated by phases of quiescence. In the following, we define the events, the phases of quiescence between avalanches and several avalanche measures, following closely the procedures of Beggs and Plenz  [18, 19]. For the event definition, we calculated the area under the positive deflection lobes between two zero crossings of the LFP (Figure  2 , box)  [18].
Therefore information and characterization of representative viruses from Nepal remain limited. A better understanding of the dynamics of RABV circulation and potential exchanges with neighboring countries is necessary and valuable for future control plans and prevention strategies. In this study, we performed the molecular characterisation of RABV isolates circulating in Nepal, based on the complete nucleoprotein (N) and glycoprotein (G) genes sequences of new isolates. We also compared the study isolates to representative viruses from other regions to place them in an international context. The combined database of rabies virus sequences has yielded insights into their phylogeography and enabled a specific examination of the timeframe of emergence of the Arctic-related clade, allowing the identification of a new and emerging Nepalese phylogenetic group of RABV.
RT-PCR and sequencing RT-PCR amplification and DNA sequencing of the N and G genes were performed as described previously  [5, [15] [16] [17] [18] [19]. Analysis of sequence data and contig assembly were performed using either the SeqMan module of the Lasergene v8. 0 software suite (DNASTAR) or Sequencher 5. 0 (Gene Codes Corporation) software. GenBank accession numbers for the complete N and G gene sequences newly acquired in this study are designated JX944565-JX944602 and JX987718-JX987749.
Phylogenetic analysis Complete N and G gene coding sequences determined in this study were analysed with respective full-length sequence datasets comprising rabies N gene sequences (n = 173, 1350 nt) and G gene sequences (n = 92, 1575 nt) available from GenBank (Table  S1 ). Multiple sequence alignments and amino acid residue analysis were performed using Clone Manager v. 9 (Science & Educational software) or ClustalX 2. 1  [20]. Maximum-likelihood (ML) phylogenies were inferred for each dataset using the GARLI v2. 0  [21]  and PAUP* v4. 0 programs  [22]. The general time reversible model with proportion of invariable sites plus gamma distributed rate heterogeneity (GTR+I+ C4) as generated by the Akaike information criterion using the program MODELTEST v3. 7  [23] , was used as the best-fit nucleotide substitution model in all cases.
Evolutionary analysis Using a select RABV Arctic-related clade dataset of 67 N gene sequences, we inferred a maximum clade credibility (MCC) tree by using the Bayesian Markov chain Monte Carlo (MCMC) method available in the BEAST package  [24]. Sequences were dated with the year of isolation, and identical sequences with the same year were excluded. The alignment used is available from the authors on request. Posterior probability values provide an assessment of the degree of support for each node on the tree. This analysis utilized the GTR+I+C4 model of nucleotide substitution. All chains were run for a sufficient length to ensure convergence, with 10% removed as burn-in. After comparison of the log likelihood values calculated for several runs through the TRACER program (http://tree. bio.
Due to the limited number of representative sequences, the relevant time-frames of emergence of the Indian subcontinent clade and its subsequent geographical diversification were not further determined in our study. A previous study based on the complete N gene sequences of several Sri Lankan viruses and only one Indian isolate, suggested that both diverged from their common ancestor around the year 1854 (95% HPD 1760-1918)  [31]. However, the large time range associated with this estimation indicates that this result clearly needs to be confirmed on a larger dataset of sequences, which should include Nepalese viruses. Previous description of a single Nepalese RABV isolate V120 suggested that this lineage was already present in Nepal in 1989  [34]. Our characterization of a further five viruses from Nepal isolated between 2003 and 2009 has confirmed that this distinct regional sub-group of Indian subcontinent clade viruses have circulated in Nepal for at least the last 24 years.
The RABV Arctic-related clade has been relatively well described with characterization of RABV from Russia, Alaska and India in recent studies  [25, 26, 35]. This clade emerged and spread relatively recently, with the most recent common ancestor dated back approximately 200 years ago  [26]. This Arctic-related clade includes the so-called Arctic and the Arctic-like sub-clades. Although RABV belonging to the Arctic-like sub-clade was already known to circulate in Nepal  [5, 35] , this study has identified for the first time the presence of two Arctic-like subclades of RABV (AL-1 and AL-3) in this country. Within the AL-1 sub-clade, we identified two Nepalese isolates belonging to the AL-1a lineage, which encompassed virus strains from India but also probably from Bangladesh and Bhutan, although for the latter phylogenetic information contained in only partial N gene sequences available in public databases was not informative enough to classify strains into either AL-1a or AL-1b lineages (data not shown)  [36, 37].
Acknowledgments The authors wish to thank  K. R. Davies ,  T. Pye  and  W. Vosloo  of the  Australian Animal Health Laboratory (AAHL), and laboratory  staff at the  Central Veterinary Laboratory, Tripureshwor, Kathmandu  for technical assistance. We thank  N. Singanallur  ( AAHL ) for review of the manuscript and  Frank Filippi  for graphical editing of Figure 2 and Figure  S1. We are also grateful to  Dr. Fayaz  of  Institut Pasteur de Teheran  for providing the RABV isolates from Iran and the virus strain 04027AFG from Afghanistan, to  Drs. de Brouker  and  Boue ,  Service de Santedes Armees  for providing the other isolates from Afghanistan and to the  Institut Pasteur Clinical Research Departement (PIRC)  for the clinical research regulatory review.
This research was supported by the  European Union Seventh Framework Programme  (FP7/2007-2013) PREDEMICS grant # 278433. We are grateful to the  Institut de Veille Sanitaire (InVS)  for financial support. The  Crawford Fund, Victorian Division, Australia  is acknowledged for their generous support that enabled technical exchange visits by G. Pant to the  Australian Animal Health Laboratory. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Microneutralisation of TOSV and PUNV The virus microneutralisation (MN) assay, previously described for phleboviruses  [18] , was adapted with minor modifications. Briefly, MN assay was performed in 96-well microtitre plates using Vero cells (ATCC CCL81). Two-fold serial dilutions from 1:10 to 1:80 were prepared for each serum and a volume of 50 mL was pipeted into 96-well plates, using an epMotion 5075 working station (Eppendorf). The two virus strains were (i) Toscana virus strain MRS2010-4319501 (GenBank accession nos KC776214-KC776216) isolated from a human case of meningitis in Southeastern France in 2010  [19] , and (ii) Punique virus T101 isolated from Phlebotomus sp. in Tunisia in 2009 (Strain Tunisie2009T101). The two virus strains were titrated in Vero cells. A volume of 50 mL containing 100 TCID 50 was added into each well except for the controls that consisted of PBS.
This study was funded in part (i) by the  French ''Agence Nationale de la Recherche'' and ''Agence Interetablissements de Recherche pour le Developpement '' through the MIE  PhleboMED  project ( ANR-08-MIEN-023 ), (ii) by the  European Virus Archive (European Union Seventh Framework Programme  under grant agreement no. 228292 ) (http://www. european-virus-archive. com) and (iii) by the  EU  grant  FP7-261504  EDENext and is catalogued by the EDENext Steering Committee as EDENext138 (http://www. edenext. eu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Functional Assessment of Hind Limb Recovery The peroneal functional index (PFI) indicating the functional alteration of the experimental nerve when compared with the opposite side was calculated by the method of Bain et al. [23]  with the following formula: PFI = 174. 9[(ePL-nPL)/nPL]+80. 3[(eTS-nTS)/nTS]-13. 4. The PFI recovery rate was defined with a score from 2100 to 213. 4, where 213. 4 represents normal function and 2100 a total absence of contraction. Hindlimb paws were marked with black ink and footprints were recorded each week on paper track, copied in a high-resolution scanner, and digitalised images were analysed. Data concerning each animal were individually identified. The parameters measured for both normal (n) and operated (e) feet were footprint length (PL, or longitudinal distance between the tip of the longest toe and the heel) and total toe spread (TS, or cross-sectional distance between the first and fifth toes).
, Biological Research Apparatus, Comerio VA, Italy). Twitches were analysed in terms of peak amplitude (A) and maximum relaxation rate (MRR), defined as the slope of a tangent drawn to the steepest portion of the relaxation curve. MRR was normalised to the total twitch amplitude (MRR/A = mean relaxation rate constant, ms 21 ), as suggested by Esau et al. [24]  who showed that MRR values are linearly related to A. Twitches were recorded with a Biopac MP150H system (sampled at 2000 Hz, low-pass filtered at 150 Hz) and analysed with the AcqKnowledgeH 3. 7. 3 software. Tetanus threshold. Muscle stimulation was induced by a pair of steel stimulating electrodes (inter-electrode distance: 4-5 mm) placed on the surface of the tibialis anterior muscle. Contractions were produced by the neurostimulator (Grass S88KH) delivering trains of rectangular pulses.
The afferent discharge was recorded (Biopac MP150H and AcqKnowledgeH software, BIOPAC Systems, Inc. , Goleta, USA) and fed into pulse window discriminators (P2MPH SARL, Marseille, France), which simultaneously analysed afferent populations. The output of these discriminators provided noise-free tracings (discriminated units) that were counted by a data analysis system (Biopac AcqKnowledgeH software BIOPAC Systems, Inc. , Goleta, USA) at 1 s intervals (in Hz) and then displayed on a computer. The discriminated units were counted and recorded on separate tracings. As previously described  [1, 2] , we recorded the response of muscle afferents after 1) a 3 min low frequency (10 Hz) electrical stimulation of the tibialis anterior muscle [simulated fatigue -Electrically-Induced Fatigue (EIF)], 2) an intra-muscular injection of capsaicin solution (655 mM in 50 mL of saline).
8 mm) were cut using an ultramicrotome (UltracutH R, Leica, Solms, Germany) and collected on SuperFrost PlusH slides. After being dried for 12 hours on a hot plate, sections were stained with a p-phenylenediamine-ethanol (70u) solution, washed in distilled water, dried for 5 hours on a hot plate and mounted with glycerol-containing medium (GlycergelH, DakoCytomation, Glostrup, Denmark). The slides were examined using an optical microscope (EclipseH E800, Nikon, Champigny-sur-Marne, France) that was associated with a high-resolution colour digital camera (DXM 1200, Nikon). The slides were digitised and analysed with the Histolab software (AlphelysH, Plaisir, France). The following parameters were measured: axon number and axonal area. The counting was performed by a robot and therefore observer-associated biases were avoided.
Microarray Data Analysis Individual microarray quality was evaluated based on QC report, pair-wise MA-plots, and box plots. Intra-array normalisation of raw signals from the 8 microarrays (corresponding to the four above-mentioned conditions in duplicate) was performed using Feature Extraction software 9. 1. 3. 1 (Agilent Technologies H ). Microarray normalised data were further exported into the Limma package, for inter-array normalisation using the quantile method. Statistical analysis was performed using the TIGR MeV (Multi-Experiment Viewer) v4. 4 software (http://www. tm4. org/mev. html) and the GeneANOVA program. Multi-way ANOVA model was implemented: first, to identify differentially regulated genes when accounting for the multiple sources of variation in the microarray experiment; second, to evaluate the effect of the main variable, the addition of calcitriol during 24 hours.
Overview of Functional Patterns Altered by Vitamin D Supplementation As a primary analysis, genes identified to be differentiallyexpressed were analysed for significant gene ontology clusters using DAVID Bioinformatics Resources (http://david. abcc. ncifcrf. gov/). Gene functional classification was used to rank gene ontology clusters by statistical over-representation of individual genes in specific categories relative to all genes in the same category on the filtered list  [27]. As a secondary analysis, biological interpretation of the data from the DNA microarrays was performed using Ingenuity Systems Pathway Analysis (http://www. ingenuity. com/). This database builds networks on candidate genes/proteins and putatively associated genes/proteins according to the data collected in previous publications.
Quantitative PCR Validation of Under-and Overexpressed Genes The samples used for the microarray experiment were reverse transcribed. Synthesis of cDNA was performed with oligo dT, RNase Out and M-MLV RT enzyme (Invitrogen H ). Four genes (Igf1, Prx, Spp1 and Tspan2) involved in axogenesis and myelination and one housekeeping gene (Gapdh) were selected for validation using the quantitative PCR technique. Before selecting Gapdh as a housekeeping gene, we checked that its expression remained steady in the gene array database. The PCR was performed using the TaqMan Gene Expression Master Mix (Applied Biosystems H #4369016, Life Technologies Corp. , California, USA) with the following conditions: 40 cycles, 15 s at 95uC and 1 min at 60uC. Probes were purchased from Applied Biosystems H. The reference numbers for each gene were: Rn01775763 (Gapdh); Rn00710 306_m1* (Igf1); Rn00576815_m1* (Prx); Rn00563571_m1* (Spp1) and Rn00574907_m1* (Tspan2).
Statistical Analysis Data processing was performed using a software program (InstatH 3. 0, GraphPad software, San Diego, California, USA). Data were expressed as mean 6 SEM and were compared by ANOVA tests. Post-hoc group comparisons were performed with Student Newman Keuls multiple post-test comparisons. Results were considered statistically significant, highly significant or very highly significant if the p-value fell below 0. 05, 0. 01 and 0. 001, respectively. 54 , respectively. When compared to the Vehicle group, only the mean improvement for the D3-500 animals was statistically significant (p,0. 05) (Figure  1A ).
Five metabolic pathways were commonly activated in both conditions: regulation of axogenesis, regulation of cytoskeleton, regulation of blood pressure, regulation of cell migration, regulation of transcription. Within the functional clustering performed with DAVID software, the pathway ''regulation of axogenesis'' was ranked number one in DRG/SC. In both types of cultures, we also observed genes that are involved in myelination. In order to validate this microarray-generated list, using the same sample material, we performed a quantitative PCR on four selected genes and found that they were upregulated, as expected (Figure  6B ).