dataesr/scientific-paragraphs-categorization huggingface dataset:
e. E17. 5, E18. 5 and PN1) were subjected to Selforganizing Map (SOM) clustering, gene ontology analysis, promoter analysis, functional classification and pathway analysis as described previously  [21, 22]. Gene Ontology and Pathway analysis were performed using publicly available web-based tool DAVID (database for annotation, visualization, and integrated discovery), ToppGene Suite (http://toppgene. cchmc. org/) and Ingenuity Pathway Analysis (IPA, Ingenuity). Upstream regulator analysis uses Ingenuity software based on prior knowledge of expected effects between transcriptional regulators and their target genes pre-compiled in the Ingenuity Knowledge Base. The analysis examines how many known targets of each transcriptional regulator are present in the user's dataset, and also compares their direction of change in the experimental condition to what is expected from the literature.
1 M Sodium Acetate, 0. 2 M Zinc Acetate pH 4. 5 and 10% PEG 3000 at both ratios. To obtain bigger crystals, an optimisation of this condition was performed using the hanging drop method and a ratio of 151 (protein5reservoir, 500 nL5500 nL). This led to the creation of reproducible crystals of 200-250 mm after 3 days at 298 K. Data collection, molecular replacement and refinement. Crystals were transferred for a few seconds in a drop (1 mL) containing a cryo-protectant solution made out of the crystallisation solution and 10% (v/v) of glycerol. After being mounted on a CryoLoop (Hampton research), crystals were flash-frozen in liquid nitrogen. X-ray diffraction intensities were collected on the ID29-2 beamline at the ESRF (Grenoble, France) with 0. 1 s exposure times. Diffraction data were collected from 2000 images; each frame consisted of 0.
1u step oscillations, over a range of 200u (Table  1 ). The molecular replacement was performed using Phaser  30  and PDB 4GD5 as a starting model. Refinement was carried out with REFMAC5 and Phenix  31, 32. The model was improved using Coot  33. The model and structure factors were deposited in the Protein Data Bank code, ID 4Q8R. Discrimination assay. The discrimination assay was performed as previously described  11. Briefly, the ability of PBP-1 to discriminate phosphate from arsenate was tested by dialysing PBP-1 against a competition buffer, made of 50 mM Tris-HCl buffer pH 8. 0, containing 140 nM phosphate (with 1 mCi of radiolabelled phosphate 32 P; Perkin Elmer NEX053011MC), and varying concentrations of arsenate (from 0. 1 mM to 100 mM). The protein was diluted to 5 mM into a buffer made of 50 mM Tris-HCl buffer pH 8.
Conversely, the background level of radioactivity in the dialysis tube corresponded to 0% binding (or 100% replacement). The replacement values were plotted using GraphPad Prism software (v. 5) and fitted to the sigmoidal equation (1): Replacement~1 00 1z10 Log R50{x ð Þ |m ð Þ ð1Þ R 50 is the ratio [arsenate]/[phosphate] yielding 50% replacement, and m is the sigmoidal slope factor. Points that do not coincide with the fitted slope (e. g. , for 100% or 0% replacement) are due to experimental errors of the system.
This topology, known as a Venus flytrap, is believed to adopt an open state while empty and to close upon ligand binding  20, 34. The structure of C. perfringens PBP-1 was also solved in another space group (P2 1 ) at a similar resolution (1. 7 A ˚) by the Center for Structural Genomics of Infectious Diseases (PDB ID: 4GD5). As expected, both structures are nearly superimposed (RSMD on a-carbon 5 0. 275 A ˚); interestingly, however, some regions adopt significantly different conformations, e. g. , two surface helices are shifted by. 1 A ˚between both structures (Fig. S2 ). The structural cause for these different conformations is not obvious from the structures, and may be due to the different crystallisation conditions and/or to the different crystal packings. Structural comparison with other PBPs.
Acknowledgements We are very grateful to  Moshe Yaniv  for helpful discussions and  Rasika Sowmyalakshmi ,  Slimane Ait-Si-Ali ,  Pierre-Antoine Defossez ,  Claire Rougeulle ,  Jonathan Weitzman  ( UMR7216 ), and  Rick Morimoto  ( Northwestern University, Evanston, USA ) for helpful comments on the manuscript. We thank  Delphine Bohl  and  Stéphane Blanchard  for assistance for retrovirus production ( Unité des Rétrovirus et Transfert Génétique, U622, Pasteur Institute, Paris, France ) and  Deborah Bouvier  for technical help. We thank  Lea Sistonen  for anti-HSF2 polyclonal antibody. We are grateful to  Olivier Bensaude  ( IBENS, Paris, France ) for allowing us to use his lab for gel-shift assays during our moving period. We thank  Bertrand Nalpas  ( Inserm, Mission Alcool-Addiction ) for continuous encouragements.
Usher syndrome vangl1/2 vang-like 1/2 VLGR1 Very large G-coupled receptor 1 ZO-1  Zonula  occludens  1 ANR 11 BSV5 011 02 ), the  LABEX LIFESENSES  (reference  ANR-10-LABX-65 ) supported by  French  state funds within the  Investissements d'Avenir programme  under reference  ANR-11-IDEX-0004-02 ,  BNP Paribas  and  LHW Stiftung. The authors are particularly indebted to  Jean-Pierre Hardelin  for his help in improving the manuscript,  Vincent Michel  and  Gaelle M.
UV-Visible spectroscopy Protein samples were fully oxidized using a solution of potassium hexachloroiridate (IV) (K 2 IrCl 6 ). Protein concentrations were typically 50 mM for UV-Vis measurements. Room temperature and high temperature UV-Vis spectra were recorded on a Cary 50 Bio (Varian) spectrophotometer equipped with a Peltiertype temperature control system at 293, 303 and 313 K. Low Temperature spectra were obtained with a Cary 300 (Varian) spectrophotometer modified to accommodate a Dewar mounted in the light path. This arrangement allows data collection at around 77 K. For this experiment, samples were diluted in buffer B containing 70% (v/v) glycerol.
(TIF) Figure  S4  Sequence alignement based on secondary structure elements of AcoP with cupredoxins of known 3D structure. (A) Secondary structure prediction of AcoP using PHYRE  [39]. Alpha helices (h), beta sheets (e) and random coiled (c) are colored in red, blue and grey, respectively. Two bottom lines: consensus sequence and consensus probability (''con-s_prob''); 9 (red) high prediction probability; 2 (cyan) the lowest probability in this prediction. A metaserver approach was required for this secondary structure prediction because we obtained very different result using single software analysis. Accordingly, a very limited set of secondary structure elements has been predicted with high confidence. (B) Sequence alignement of secondary structure elements of AcoP (predicted using PHYRE, see A) with well-known cupredoxins.
Acknowledgments We gratefully acknowledge the contribution of  Mireille Ta  for technical assistance,  Remy Puppo ,  Regine Lebrun  and  Sabrina Lignon  ( Proteomic Analysis Center, Marseilles, France ) for mass spectrometry analyses,  Deborah Byrne  for technical assistance with plasmids constructions,  Violaine Bonnefoy  for providing us specific antibodies and  Olivier Ilbert  for kindly providing us a software to deconvolute our spectroscopic data. We also thank  Marianne Guiral ,  Pascale Infossi  and  Ursula Jakob  for helpful discussions and for reviewing the manuscript. The Proteomic Analysis Center of IFR88 is part of  MaP (Marseille Proteomique, IBiSA ). The authors are grateful to the  EPR  facilities available at the  Aix-Marseille University EPR center. Financial support from the  TGE RPE FR3443  for conducting the research is gratefully acknowledged.
Financial support from the  National French Network for EPR equipments (''Tres Grands E ´quipements pour la Resonance Paramagnetique E ´lectronique' ') for conducting the research is gratefully acknowledged. Additional funding was provided by  Agence Nationale de la Recherche ,  Bioenergie ,  Centre Nationale de la Recherche Scientifique -Aix-Marseille Universitee. Magali Roger  has a fellowship of the  French Ministry of Research (Ministere de l'Enseignement Superieur et de la Recherche). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Statistical analyses Statistical analyses were performed using SAS ® software (SAS Enterprise Guide 4. 3 for Windows, SAS Institute Inc. , Cary, NC, USA). Data are presented as means ± standard deviation (SD) unless stated otherwise. Statistical significance was set at p < 0. 05. Given the exploratory nature of the study, no sample size calculations were performed. Despite the attempt to select a group of healthy controls with a mean age comparable to the AD patients, there was an age difference at baseline between the healthy controls (n = 98) and AD patients (n = 84) (respectively 70. 4 ± 10. 1 versus 74. 2 ± 7. 6 years, p = 0. 005). To overcome this imbalance at baseline, it was decided to exclude the five oldest AD patients and the five youngest healthy controls from the dataset prior to the main statistical analyses.
Indeed, this resulted in a better balance between groups with respect to age (Table  1 ), while other subject characteristics at baseline did not change. Therefore, data from 93 healthy controls and 79 AD patients were used for the analyses presented here. Differences between AD patients and healthy controls were primarily analyzed using an independent samples t-test. The non-parametric Mann-Whitney test was used for parameters with a non-normal distribution. As a sensitivity analysis, additional between-group analyses were performed using analysis of covariance (ANCOVA) to correct for the potential confounders 'age' (continuous; years), 'nutritional supplement use' (dummy variable; yes/no), 'use of lipid-modifying agents' (dummy variable; yes/no), and 'years of education' (continuous; years).
4% versus 46. 2%). These differences may have influenced the results. However, analyses on data of 66 pairs of age-and gender-matched subjects and excluding subjects using nutritional supplements yielded similar results (data not shown). 2) No data were collected on dietary intake of the study subjects, so the possible contribution of (differences in) dietary intake (specific (micro)nutrients and/or caloric intake) on the results cannot be determined. 3) Due to the exploratory character of the study, no correction for multiple testing was performed. To confirm current study findings, further research is warranted. 4) To avoid the influence of regional differences in nutrient levels via for instance different dietary habits or food fortification, this substudy was performed in one small country with relatively homogenous food habits, the Netherlands.
MABN intended to study all the features of Tubu people who dwelt on the Northeastern rim of Tenere desert. Anthropobiology, population genetics, and tropical medicine were the covered topics. This expedition was successful in the field, but the organization was afflicted by tragic events concerning scientific and logistic heads that elicited a dark aftermath, so only some results concerning zoology  [11, 12]  and Tubu physiology  [13] [14] [15]  have been published so far. The present article represents therefore the first public disclosure of detailed data concerning the health and sanitary status of Tubu people dwelling in Northeastern Niger.
Conclusions Data from a more recent book about the Tubu suggests that over the past 4 decades, no major socioeconomic changes have occurred in this society, apart from the spread of car and truck transportation  [4]. In fact, the overall socioeconomic level of Niger has improved very slightly: the gross domestic product (GDP) per capita in Niger in 1970 was 97 US $ and ranked 168th in the world; in 2012, the GDP per capita was 395 US $ and ranked 205th  [34, 35]. It therefore appears that the results from the MABN survey are still topical concerning the anthropology, epidemiology, and health and sanitary status of Tubu nomads in Niger. Only the malaria threat in Djado appears to be ruled out because recent satellite views have shown that the swampy areas around the ghost citadel are now dry and salty  [36].
Production of BbgIV A single colony from a freshly prepared sub-culture of E. coli DH5␣ cells, harbouring the plasmid pBL-2-K2, which was constructed from pBluescript SK (+) (accession number X52324) (Stratagene, USA) and carried the gene encoding for BbgIV  [18] , was transferred into 10 mL Luria Bertani (LB) medium with pH 7 (containing 100 gmL -1 ampicillin) and grown for 8 h at 37 • C and at 200 rpm. An aliquot of this culture was used to prepare the inoculum (200 mL of LB medium supplemented with 100 gmL -1 ampicillin and incubated for 10 h at 37 • C and at 200 rpm). The E. coli cells were harvested by centrifugation (8000 × g, 15 min, 4 • C), suspended in sterilised phosphate buffer saline (PBS) at pH 7. 0 and used to inoculate a 5 L bioreactor (Applikon, Gloucestershire, UK), at a starting OD 600 nm of 0.
Covalent attachment of BbgIV to glyoxal-and amino-ethyl-agarose beads Glyoxal activated agarose covalently binds to lysine amino groups, while amino-ethyl activated agarose covalently binds to acidic amino acids like aspartic and glutamic acids. Regarding glyoxal agarose, the immobilisation yield (Yi) was very low and did not exceed 3% for all types of beads at pH 10 (Table  1 ). Also, no increase in Yi was observed when the immobilisation was conducted at lower pH values, such as pH 8 and 9 (data not shown). The low Yi values obtained using glyoxal agarose were most likely due to the presence of only 21 lysine residues out of 1052 amino acids in each monomer of BbgIV (see enzyme sequence with accession number ABE00939 in NCBI database). Moreover, the location of these residues is not known yet.
cinerea  [5, 6, 16, 17, 25]  it was not included in these assays at different concentrations but only at 0. 5 mM as positive control. The IC 50 of pterostilbene was therefore used for comparison. Resveratrol (0. 5 mM) was systematically included in each bioassay as reference. DMSO alone did not inhibit the mycelial development (data not shown). Compound 8 appeared highly interesting since it showed high antimicrobial activity against both pathogens. It was more efficient than pterostilbene (2), generally described as the most active resveratrol analogue, on B. cinerea. This highlights the interest of this disubstituted stilbene. According to the results obtained with P. viticola, compound 4 also showed a high activity whereas compounds 1 and 6 were less active. Interestingly, compound 7 showed a high antimicrobial activity on B.
Acknowledgments We thank the  Conseil Régional de Bourgogne and Bureau Interprofessionnel des Vins de Bourgogne  for financial support,  Adrian Variot  for technical assistance, and  Arnaud Haudrechy  for helpful comments concerning the manuscript. Malik Chalal benefited of a PhD grant from  Algerian government  ( Ministère de la Recherche et de l'Enseignement ), which is sincerely acknowledged.
In response to this evidence, the prenatal assessment of fetal growth and gestational age in utero by means of ultrasonography was adopted as standard practice in prenatal care throughout the world. The adequacy of fetal size is currently assessed by comparing the measurements of fetal anatomical parameters at a given gestational age captured through ultrasonography with reference percentiles of fetal size derived from populations of fetuses whose growth was assumed to be normal. These same reference percentiles can be used to estimate gestational age from observed fetal size. The most commonly used reference charts of size by gestational age were developed based on data from populations of fetuses in the United States or Europe. Since 1981, concerns have been raised that such charts might not be appropriate for use in other ethnic groups which may experience different patterns of fetal growth  [2] [3] [4].
Biparietal diameter (BPD) Head circumference (HC) Abdominal circumference (AC) Femur length (FL) Transcerebellar diameter (TCD) Humerus length (HL) Fetal Foot length (FFL) At each examination, all measurements are to be obtained three times from three separately generated ultrasound images and uploaded electronically (with the associated images) to the data management system. The mean of the three measurements of each parameter will be used for clinical management purposes as per local protocols. In addition, a full morphological evaluation (abnormality scan) will be conducted at 18-24 weeks following standard practices at each centre. Fetuses diagnosed with any minor abnormalities will be managed according to local clinical guidelines. If the clinical decision is to continue with the pregnancy the case will remain in the study.
Ultrasound volume acquisition protocol The ultrasonographic equipment that will be used in the study will allow for acquiring and storing 3-dimensional images. This feature is of critical importance for data quality purposes. Stored 3-dimensional images (volumes) could be used at a later stage to retake measurements that have been identified as erroneous. Except for a transvaginal scan during the first research visit (8 0/7 -12 6/7 weeks), 3D volume data will otherwise be acquired using a transabdominal probe. All volumes shall be systematically labelled using the comment feature of the Voluson E8 (GE Healthcare, Germany) Expert system (e. g. "LA1"). Recommended Image settings: At.
Skin fold caliper measurements (Harpenden) will be used to document soft tissue distribution  [17, 24]. These skin folds will include the triceps fold, anterior thigh fold, sub-scapular skin fold, and abdominal flank skin fold that will be made at each site twice and averaged. This data will be used to estimate per cent body fat and lean body mass as an index of neonatal growth outcome. Other parameters of neonatal body composition will include ponderal index and birth weight  [25].
Safety of ultrasonographic assessment Ultrasonography in pregnancy is considered a safe procedure and in more than 30 years no fetal harm has been reported with use in the low-intensity range of gray-scale imaging (no Doppler), which is the technology that will be used in the proposed study  [29]. Serial ultrasonography for research purposes according to schedules similar to the one we propose has been approved previously in the context of other studies  [30] [31] [32] [33]. Following a recommendation of the WHO Scientific and Ethical Review Group, we conducted a systematic review and meta-analysis to evaluate the safety of human intrauterine exposure to ultrasonography  [32]. We systematically searched electronic databases, reference lists and unpublished literature according to the following criteria: Types of studies: Trials and observational studies that assessed short and long term effects of exposure to ultrasonography during pregnancy.
Types of participants: Women submitted to ultrasonography in pregnancy and their offspring. Types of exposure: B-mode or Doppler sonography during any period of pregnancy, for any number of times, using any equipment and transducers. Types of outcome measures: 1) adverse maternal outcomes, 2) adverse perinatal outcomes, 3) abnormal childhood neurological development, and 4) childhood malignancies. The electronic search identified 6716 citations and 63 were selected for full text evaluation. Additionally, 19 citations were identified from secondary sources. A total of 58 references reporting data of 38 different studies were included: 16 clinical trials, 11 cohorts, and 11 case controls. Ultrasonography in pregnancy was not associated with adverse maternal effects, impaired physical or neurological development or increased risk for malignancies in childhood.
Sample size The total sample size will be 1400 pregnant women and their infants. Each country centre will collect data from 140 women. This number is sufficient for the development of local centile growth charts with a high level of precision, accounting for exclusions to final analysis due to inability to follow up and occurrence of pregnancy complications  [34, 35]. The sample size needed for the estimation of a specific percentile was computed using the following formula  [36] : n ¼ 1 þ z 2 α =2 À Á %SE P α %CV 2 where z α is the standard normal deviation corresponding to the percentile being estimated, % SE C α is the expected percentage standard error of the percentile and % CV is the percentage coefficient of variation. Sample sizes were computed for 5 different parameters (biparietal diameter, abdominal and head circumference and femur and humerus length) and for 3 different percentiles: 5%, 10% and 50%.
Data management Data will be collected via an internet based data management system as done with other WHO coordinated studies. The online data collection system will allow for real time solutions of queries or other problems in data collection, such as missing or non-valid data as well as for online checking of images by the international coordination unit. All data will be stored in a GCP compliant server, and data transmission will be encrypted to assure data integrity and patient confidentiality. Access to the data management web system will be password protected and only authorized users will have access. Data changes will be documented. The system will maintain an audit trail, data trail and edit trail as well as back up of the data. Data entered into the web system will be checked by the coordinating unit at WHO for completeness, accuracy, reliability and consistent intended performance.
The primary use of received dose (dose*adherence) as opposed to treatment dose from double-blind RCTs allowed for the assessment of antifracture efficacy by a dose that accounts for the low adherence in several recent large trials  [24, 25]. Any lower received dose than 482 IU per day did not reduce fracture risk at either any non-vertebral site or the hip. Similarly to the data on fall prevention with vitamin D, at the highest received dose of vitamin D (>482 IU per day) the prevention of non-vertebral fractures was present in all subgroups of the older population independently of age and type of dwelling  [5]. Notably, there was a suggestion that vitamin D3 was superior to vitamin D2 for both fall and fracture prevention  [5, 6]. A participant level meta-analysis from 11 double-blind RCTs (31022 individuals with mean age 76 years, 91% women sustaining 1111 incident hip and 3770 nonvertebral fractures) assessed the effect of actual dose of vitamin D on fracture reduction.
Acknowledgments This study was granted by the  Commision of the European Communities ; project  FP7-KBBE-2007-1 'Rednex'. G. Cantalapiedra-Hijar  gratefully acknowledges the receipt of a scholarship from  PHASE department (INRA). The authors thank  Adisseo (Commentry, France)  for financial support to conduct the study. They also thank  C. Cossoul ,  A. S. Bage ,  J. Fernández ,  T. Garcia  as well as the experimental unit "Les Cèdres" for technical assistance.
This study was funded by the  Institut Pasteur , the  Centre National de la Recherche Scientifique  ( CNRS-UMR3525 ), the  French National Research Agency  ( ANR-2012-Blanc SVSE3-DynamINT ), the  French Government 's  Investissement d'Avenir program ,  Laboratoire d'Excellence "Integrative Biology of Emerging Infectious Diseases " (grant  nuANR-10-LABX-62-IBEID ) and the  European Union Seventh Framework Programme  ( FP7-HEALTH-2011-single -stage) ''Evolution and Transfer of Antibiotic Resistance'' (EvoTAR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.