dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements The present work was commissioned by the  Addition of Nutrients to Foods Task Force of the European branch of ILSI (ILSI Europe). Industry members of this task force are  BASF SE, Bunge Europe, Coca-Cola Europe, Danone ,  DSM ,  FrieslandCampina ,  Kellogg Europe ,  Mars  and  Red Bull. This publication was coordinated by  Athanasia Baka  and  Dr Christophe Matthys ,  Scientific Project Managers at ILSI Europe. For further information about ILSI Europe , please email info@ ilsieurope. be or call þ  32 2 771 00 14. The opinions expressed herein and the conclusions of this publication are those of the authors and do not necessarily represent the views of ILSI Europe, nor those of its member companies. The  ILSI Europe Expert Group on 'Mapping Low Intakes of Micronutrients Across Europe'  wishes to thank  Belinda Antonio  and.
e). Bead mechanical properties. The Young's modulus of the different Ca-alg beads were calculated from the measurement of the force needed to compress the beads at a constant speed up to a set percentage of their initial diameter (final height equivalent to 40% of the initial diameter). The higher the Young's modulus, the more the material resists to compression. Our data (Fig. 2 ) demonstrated that the Young's modulus significantly increased when collagen was added to Ca-alg or when the bead is coated by a PLL layer, compared to pure Ca-alg beads (1. 6 fold (p,0. 05), 1. 7 fold (p,0. 05), respectively). Moreover, the simultaneous incorporation of collagen and PLL layer resulted in a cumulative effect on the Young's modulus (increase of 1. 9 fold (p,0. 01), in comparison with Ca-alg beads).
Ethics This study was based on analysis of routinely collected, patient monitoring data from the programmes for acute malnutrition. A Memorandum of Understanding to implement and analyse the surveillance system was signed with the Ministry of Health. In agreement with the Ministry of Health clinical and therapeutic patient data are routinely collected for patient and programme monitoring; as such, no formal ethics approval from institutional review boards and/or written patient consent were required by either the Ministry of Health, Nigeria, or the rules of the MSF Ethical Review Board. Local health authorities were informed of the potential publication of findings, with approval from the Nigerian health authorities. We followed the Declaration of Helsinki, aiming to provide assurance that the rights, integrity, and confidentiality of participants were protected  [10].
The sample size was calculated based upon 5 person households with one eligible child, a maximum expected prevalence of 15%, a design effect of 2. 0, a non-response rate of 10% and a precision of 5% to be 527 households and was rounded up to 600 (30620). A household was defined as a group of people sleeping and eating together from a common cooking pot. Within each household all the children aged between 6 to 59 months had their, age, sex and whether they were receiving treatment for severe acute malnutrition (SAM) recorded; their MUAC was measured and they were tested for oedema. At cluster level, GPS position, ethnic group and the price of the main food items were also collected. An independent PPS survey was conducted quarterly, using the same sampling frame where weight and height were also measured and a 3 month retrospective mortality estimate obtained (data not shown).
The Survey Teams Physically fit home visitors, who could speak English and the local language, read, write and count accurately, were recruited from both the Ministry of Health and MSF. There were 3 teams of two home visitors (one male and one female), each surveying two clusters per day. The teams were not assigned to particular clusters to avoid systematic bias. They were closely followed by the supervisor during all data collection. They attended five days training focusing on the aims of the surveillance system, the importance of data collection and how to avoid selection, information and measurement biases; followed by practical training taking anthropometric measurements and testing for oedema with a formal standardisation test. Refresher training was repeated several times during the surveillance follow-up and the standardisation test to assess the precision and accuracy of the measurements  [13]  was repeated quarterly and whenever a new team member was recruited.
Data Collection The ages of children were ascertained with the help of a local events calendar. If a child's age was uncertain, his/her eligibility was judged using a stick marked at 60, 65, 75, 85, 95 and 110 cm -children 65 to 110 cm were then included in the sample. Children meeting the criteria for severe acute malnutrition (SAM: MUAC,115 mm and/or bilateral oedema) were referred for treatment. Single data entry was performed on ENA Delta  [14] ; a plausibility check was run to identify duplicate entries, missing values, age distribution, sex and age ratio, digit preference, design effect and if cases were randomly distributed or aggregated over the clusters by calculation of the index of dispersion and comparison with the Poisson distribution for global acute malnutrition (GAM) and SAM.
MUAC outliers were identified using the SMART  [14]  procedure of flagging those values which were more than 3 standard deviations from the mean. This check was performed for the overall survey and by team on a daily bases in order to exclude/replace enumerators without the requisite skill. Some of the clusters, which had been previously removed, were subsequently re-selected. As the previous intervention in the cluster could influence the data collected subsequently, only data collected during the first selection of a cluster are included in this analysis. Variables Three variables were considered as outcomes: (i) absolute value of the child's MUAC; (ii) GAM prevalence defined as MUAC,125 mm or bilateral oedema; and (iii) SAM prevalence defined as MUAC,115 mm or bilateral oedema. MUAC was measured as a continuous variable and GAM and SAM prevalence as dichotomous variables.
Description of the Nutritional Surveillance System A total of 31 cross sectional surveys were performed; 21 fortnightly from June 2010 to April 2011 and then 10 monthly until February 2012. A total of 108 different clusters were surveyed; 19 were re-selected more than once and the data from second and subsequent surveys of the same cluster excluded from the analysis. Figure  1  shows the mean absolute MUAC and Figure  2  the prevalence of GAM and SAM during this period. The point and period program coverage was computed every four weeks and are presented in Figure  3.
Acknowledgments We thank the  Ministry of Health of Jigawa state , the Gunduma health system board of  Jigawa  and the  Kazaure Gunduma council  for their support in this project as well as  Stanley Chitekwe  from  UNICEF. We thank the field teams of MSF in Kazaure, our dedicated supervisors, investigators, assistants, drivers and logisticians for their support in gathering data. In particular, we wish to thank the  Head of Mission ,  William Hennequin , for his support, advice and operational expertise, as well as the supervisor of the surveillance team,  Lola Omoniyi , for her dedication and work on ensuring the data collection in this study. We are also thankful to  Prof. Michael H Golden  for his guidance during the study and to  Dr. Francesco Checchi  for reviewing. We wish to thank the village authorities and all the families from investigated villages for their participation in this project.
This mechanism is very well-conserved throughout evolution. Ion selectivity of P-ATPases follows the HSAB rule and is determined by conserved amino acids, located at conserved positions in the TM domain of the transporter. For instance, Ca 2+ -ATPase binds Ca 2+ thanks to Asp, Glu, Thr, and Asn residues located in TM helices 4, 5, 6, and 8. The same residues are found in the K + -and Na + -binding sites of the Na + /K + -ATPase  (Bublitz et al. , 2010). Metal transporting P IB -ATPases have been classified into five subfamilies on the basis of sequence homology  (Arguello, 2003). Interestingly, this study reveals that each subfamily possesses conserved amino acids in TM helices 6, 7, and 8, likely to be involved in metal coordination, and these data, collected from in silico analysis of 249 sequences, corroborate biochemical data obtained on P IB -ATPases (Supplementary Table  1 ).
ACKNOWLEDGMENTS The authors received no specific funding for this work. The  laboratory of Olivier Neyrolles  is supported by the  Centre National de la Recherche Scientifique (CNRS) , the  Fondation pour la Recherche Médicale (FRM) , the  Agence Nationale de la Recherche , the  European Union , and the  Fondation Mérieux. The funders had no role in the decision to publish this article or in its preparation.
360. 3 nN for MOR256. 17/b2AR doublets. This set of data demonstrates that significant heterotypic cell adhesion can be induced by the overexpression of an OR in one cell, and of another OR or the b2AR in another cell. The separation forces measured for homotypic and heterotypic doublets are in the same range of values (1. 2,SF,1. 8 nN for homotypic adhesion, 0. 8,SF,2. 7 nN for heterotypic adhesion). Statistical comparisons revealed some significant differences between the mean separation forces measured for the different groups (Fig. 5B ). However, as the adhesion strength depends on the number of molecules exposed at the plasma membrane and our model does not control for expression level of the different constructs in transfected cells, comparison of the separation forces does not lead to any strong conclusions regarding the possible differences in adhesion strength under homotypic and heterotypic interactions.
Acknowledgments The FLAGRhob2AR-iGFP and HA-I7 constructs are a kind gift from  Dr S. Firestein ' s laboratory (Columbia University, NY, USA ), the RTP1S construct is a kind gift from  Dr J. Mainland  and  Dr H. Matsunami 's laboratory ( Duke University, Durham, USA ). The pCAGGS-iresGFP vector was kindly provided by  Dr S. Garel 's laboratory ( ENS, Paris, France ) and the a7-5HT-pmt2001 by  P. -J. Corringer  and  U. Maskos  ( Pasteur Institute, Paris, France ). We thank the IFR83 Imaging plateform for confocal microscopy analyses, and  Drs. Isabelle Dusart ,  Laure Bally-Cuif  and  Charles Greer  for their useful comments on the manuscript.
This work was supported by the  Centre National de la Recherche Scientifique, UniversitePierre et Marie Curie (UPMC) ,  Agence Nationale de la Recherche  (grant  ANR-2010-BLAN-1401-01  to AT),  Investissements d'Avenir program  managed by the  Agence Nationale de la Recherche  under reference  ANR-11-IDEX-0004-02  and by  National Institute of Health  (grant  5R01DC012441  to AT). The team is affiliated with the  Paris School of Neuroscience (Ecole des Neurosciences de Paris Ile-de-France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Whether these variations in clinical endpoints and survival curves represent misreporting or a flaw is not the point of this article. However, it makes the JUPITER results at least doubtful and not consistent  [136, [139] [140] [141] [142] [143] [144] [145]. In any case, it is now apparent that experts independent from the sponsor should have a look at the raw (hospital) data of each patient, including those who do not have any complication during the trial, before validating (freezing) the dataset and starting the statistical analysis. Only one version of the clinical results should exist and the statisticians should be totally independent from the sponsor and totally free of any conflict of interest. External audit should be an obligation to re-introduce confidence regarding the validity of the datasets of commercial trials.
Acknowledgment We thank the participating children and their guardians. We are grateful for the support of  Médecins sans Frontières teams in Switzerland, Geneva and in Monrovia and Nimba County, Liberia. We acknowledge the study-team, including the physician assistants:  Colee R. Marnia Jnr. ,  Tarnue Jallah ,  Mohamed K. Mansalay , the laboratory technicians:  V. Yatta Walker ,  Andrew Samorlu ,  Mathilda Clinton ,  Tobias H. Johnson ,  Mathew G. Kwaidah ,  Linda Nyamedor , nurses:  Felicia George ,  Suwulubalah Molubah Dorborson ,  Masu Sasay ,  Wannie Wesley ,  Oretha Page ,  Rachel G. Fannoh ,  Nyama K. Loila , nurse aids:  Kononon Karduan ,  Roosevelt Suomie ,  Margarethe Scere ,  Saretta F. Glee ,  Lois M. Dolo , and data clerks:  Chabe Jobe ,  Isaac Williams. We also thank the  CHC  staff.
Background: The arylamine N-acetyltransferases (NATs) are a unique family of enzymes widely distributed in nature that play a crucial role in the detoxification of aromatic amine xenobiotics. Considering the temporal changes in the levels and toxicity of environmentally available chemicals, the metabolic function of NATs is likely to be under adaptive evolution to broaden or change substrate specificity over time, making NATs a promising subject for evolutionary analyses. In this study, we trace the molecular evolutionary history of the NAT gene family during the last ~450 million years of vertebrate evolution and define the likely role of gene duplication, gene conversion and positive selection in the evolutionary dynamics of this family. Results: A phylogenetic analysis of 77 NAT sequences from 38 vertebrate species retrieved from public genomic databases shows that NATs are phylogenetically unstable genes, characterized by frequent gene duplications and losses even among closely related species, and that concerted evolution only played a minor role in the patterns of sequence divergence.
The aim of the present work was to thoroughly examine the molecular evolutionary history of the NAT gene family during the last ~450 million years. A phylogenetic analysis of 77 NAT homologous nucleotide sequences from 38 vertebrate species retrieved from genomic databases was used to determine the likely contribution of gene duplication, gene conversion and positive selection to the evolutionary dynamics of this family. A special emphasis was put on the study of the last ~85 million years of primate NAT evolution by determining the NAT coding sequences in 13 additional primate species. The results of this work greatly improved our understanding of the evolutionary regime that has shaped the NAT protein-coding sequence: it allowed us to clarify the paralogous and orthologous relationships among the NAT genes in vertebrate species, date the gene-duplication events giving rise to the human NAT gene family, and identify episodes of adaptive evolution at specific sites and domains of the protein.
Phylogenetic analysis of vertebrate NAT sequences To study the molecular evolution of the NAT gene family in vertebrates, we retrieved all available NAT-homologous sequences from public genomic databases and compiled a dataset of 77 NAT coding sequences from 38 species representing all major vertebrate taxa ('vertebrate dataset'). These 77 sequences included 68 full-length open reading frames (ORFs) with sizes ranging from 864 to 870 bp and 9 partial coding sequences containing 15 to 166 missing nucleotides. In most species, we identified one or two distinct NAT sequences but in some others, up to five functional NAT genes were found (7, 2 and 1 species harbored 3, 4 and 5 distinct sequences, respectively). A second NAT sequence was identified in Dipodomys ordii and Vicugna pacos but the corresponding ORFs were missing 300 and 500 nucleotides, respectively, so they were not included in the final dataset.
Maximum-likelihood analysis of selective pressures in vertebrate NAT sequences Since some aspects of NAT evolution are likely driven by xenobiotic exposure, we investigated the possible role of natural selection in the evolutionary history of this gene family. To test for evidence of positive selection acting at specific sites of the NAT coding region or along particular branches of the phylogenetic tree, a series of nested likelihood ratio tests (LRTs) using different sets of site-specific and branch-specific models were carried out using the codeml program of the PAML package  [26]  (Table  2 ). When applied to the DNA codon alignment of the full vertebrate dataset (n = 77 sequences), LRTs of site-specific models indicated both varying ω ratio among sites (M0 vs. M3: P < 0. 0001) and positive selection at a small subset of sites (M2a vs.
NAT sequence evolution and analysis of selective pressures in the primate lineage A more thorough investigation of the evolutionary history of the NAT gene family was conducted in primates by extending the analysis to 13 additional primate species (including 3 hominoids, 8 Old World and 2 New World monkeys) in which NAT nucleotide sequences were determined for the first time. Two functional NAT genes were found in all 13 species, whereas a third NAT sequence, abolished by frameshift mutations and highly similar to the human pseudogene NATP, was found in ten of them. In all, the full primate data set comprised 59 nucleotide sequences from 22 primate species, including 17 database sequences and 42 newly generated ones. Whereas functional sequences were all of the same length (a full NAT ORF of 870 bp), pseudogene sequences displayed considerable length variation due to the significant number of indels disrupting NAT ORF (ranging from 865 bp for Colobus guereza NATP to 881 bp for Gorilla gorilla NATP), resulting in a multiple alignment of 890 sites (Additional file 5).
Obviously, we cannot exclude the possibility that similar reasons may explain the absence of NATP in platyrrhine species. However, the high number of trials performed (11 different primer pairs tested, arranged on different parts of the gene including the 5' and 3' regions, and varying PCR conditions) make this possibility unlikely and rather support a true absence of the pseudogene in Platyrrhini and Hylobates lar. The phylogenetic analysis also demonstrates that NAT1 and NAT2 paralogs found in Microcebus murinus and Tarsius syrichta are the result of independent gene duplication events that occurred after the divergence of these species from the simian lineage and after the divergence of Strepsirrhini and Tarsiiformes. Because no gene conversion was detected with any of the six recombination detection methods for any pair of sequences in the primate dataset, we can exclude concerted evolution as a possible explanation for the greater similarity of NAT paralogs within M.
49, P > 0. 05). Detailed analysis of the tree using the free-ratio model of codeml did, however, identify a number of branches with ω values higher than 1. 0, the strongest evidence being found in the lineage leading to Strepsirrhini (branch a, Figure  5 ), consistent with the full vertebrate dataset analysis results. The branch-site tests, performed at both the branch and clade levels (Figure  5 ), identified one branch evolving at an elevated rate compared to other branches of the phylogeny (B1, P = 0. 011) as well as three clades within the set of orthologous NAT2 sequences with evidence of positive selection (C7, P = 0. 019; C8, P = 0. 040; C9, P = 0. 017, C8 and C9 being component clades of C7). These results were, however, no longer significant after applying the Bonferroni correction for multiple comparisons.
*Statistically significant branch-site tests at the conventional P-value threshold of 0. 05 (not corrected for multiple testing). **Statistically significant branch-site tests at the Bonferroni-corrected threshold of 0. 0056 (9 tests). absent in the structures of prokaryotic NATs. This loop located in domain II is associated with the domain III βsheet, apparently providing structural stability and limiting active site access  [33]. Also, the C-terminal tail is not α-helical, as is the case for the bacterial NATs, but is instead a coil that reaches around and associates with the active site cleft, thereby playing a key role in defining the size and shape of the active site pocket. The well-known relationship between the primary sequence of eukaryotic NATs and the structural and functional features of these enzymes prompted us to examine the variation of ω along the NAT protein sequence in the different datasets investigated: (i) the vertebrate dataset, including the full set of 77 vertebrate sequences as well as a subset of 55 mammalian sequences, and (ii) the primate dataset, including the full set of 43 primate sequences as well as the subset of 19 simian NAT2 orthologous sequences.
We looked at the variation of the posterior mean of ω as estimated by the codeml program under the site-specific model that best fitted the data (Figure  6 ). Moreover, we tested for significant differences in the mean ω value between different parts of the protein (domain I, domain II, interdomain, domain III, 17-residue insert, C-terminal tail) and different sets of sites (residues involved either in CoA binding or in substrate binding, Additional file 6: Table  S2  and Additional file 7: Table  S3 ). Our results revealed a significant heterogeneity of ω between the four protein domains (domain I, domain II, interdomain, and domain III) in the four datasets analysed (Kruskal-Wallis P values ≤ 0. 03). More specifically, the first domain was found to evolve under more selective constraints, with a mean ω value being significantly lower than those observed for domain II, domain III or the rest of the sequence (Mann-Whitney P < 0.
05, Additional file 6: Table  S2  and Additional file 7: Table  S3 ). By contrast, domains II and III did not show any differences in their mean ω value when compared to the rest of the sequence (Mann-Whitney P > 0. 05). These results were consistently observed in the four datasets examined. Besides, the interdomain region, 17-residue insert and Cterminal tail were all found to evolve in vertebrates under more relaxed selective constraints than the rest of the sequence, as reflected by significantly higher ω values (Mann-Whitney P = 0. 03, P = 0. 02, P = 0. 007, respectively). A similar finding was observed for the C-terminal tail in the mammalian (P = 0. 06), primate (P = 0. 01) and simian NAT2 (P = 0. 03) datasets, consistent with the major role of this region in determining arylamine substrate specificity.
Interestingly, the mean ω value of the set of sites involved in CoA binding was strikingly high when compared to the mean ω value at the global protein level in vertebrates (0. 70 vs. 0. 34, Mann-Whitney P = 0. 002), mammals (0. 77 vs. 0. 40, P = 0. 003) and primates (0. 73 vs. 0. 47, P = 0. 011). Conversely, adaptive molecular evolution was evidenced in the simian NAT2 dataset for those sites involved in substrate binding compared to the full set of sites in the protein (1. 31 vs. 0. 66, P = 0. 044).
The ongoing sequencing of entire genomes from various organisms is providing unparalleled opportunity to trace the evolutionary history of the NAT gene family by enabling the inference of the phylogenetic relationships among NAT sequences over a wide range of taxa. Several previous surveys of public genomic databases have retrieved NAT-like sequences and documented the distribution of NAT genes across all major clades of life  [1, 2, 45]. The last survey by Glenn et al. [2]  provided an exhaustive annotation of NAT-homologous sequences recovered through inspection of 2445 genomes encompassing all major taxa from bacteria and archaea to protists and fungi, to animals. The same investigators also performed phylogenetic analyses of the retrieved NAT-homologous protein sequences, providing a broad perspective of NAT evolution.