dataesr/scientific-paragraphs-categorization huggingface dataset:
Read numbers were normalized relative to qPCR data on a set of selected regions (Supplementary Table  S6 ) using the ratio between WT and mutant strains. The ratio of ChIP-qPCR values (V) between WT and mutant strains was calculated for each selected region (R qPCR = V qPCRmut /V qPCRwt ). In parallel, the ratio of ChIP-seq reads (N) between WT and mutant strains was determined for the same region (R seq = N seqmut /N seqwt ). The normalization coefficient between ChIP-qPCR and read ratios was then calculated for each region (Q = R qPCR /R seq ). The median of normalization coefficients between ChIP-qPCR and read ratios was used for ChIPseq data normalization (Supplementary Table  S7 ).
Yeast core Mediator is composed of 21 subunits since it lacks the 4 Cdk8 module subunits. The Med31 Mediator subunit escaped mass spectrometric identification  (8) , leading to 20 core Mediator subunits that could be detected by this approach. Our mass spectrometry analysis showed that all 20 Mediator subunits were present in Mediator complex purified from med17 mutants and a WT strain (Figure  1B , Mediator purification). Even though no peptides were initially detected for Med21 subunit (a small Mediator subunit of 16 kDa) in med17-98 mutant, the presence of this subunit in med17-98 Mediator complex was confirmed by a second data acquisition identifying 2 unique peptides and our western blotting analysis with anti-Med21 antibody (Supplementary Figure  S3B ). Taken together, our data strongly suggest that med17-98, 444, 504 and 670 mutations did not compromise Mediator integrity.
Effects of med17 mutations on chromatin occupancy of PIC components on the inducible GAL1 gene To address the recruitment of PIC components to an inducible yeast gene, ChIP experiments were performed with Mediator, Pol II and GTFs in med17 mutants on the GAL1 gene. The association of Mediator (Med5 subunit), Pol II, TFIIH core (Rad3 subunit), TFIIH kinase module (Kin28 subunit) and TBP were analyzed by ChIP at 45 min of galactose induction (data not shown). The association of PIC components was generally affected in the same manner as for the three constitutively expressed genes, with med17-504 being an exception with reduced Mediator recruitment and unmodified Rad3 and TBP recruitment to the GAL1 promoter region at 45 min of galactose induction. Two med17 mutants were chosen for further experiments to address the kinetics of the GAL1 gene induction: med17-444, since it is the only mutant that affected TBP recruitment to the GAL1 promoter and med17-504, since its effects on the GAL1 gene differ from those on the ADH1, PYK1 and PMA1 genes for several PIC components.
normalization step cannot be applied in situations where occupancy increases or decreases genome-wide. To detect the potential global effects of Mediator mutations on PIC component occupancy, we performed the following normalization step. A count of reads was determined on the promoter regions of Pol II-transcribed genes for Med15, Rad3, Kin28 and TBP, and on Pol II-transcribed gene ORFs for Pol II and then normalized relative to qPCR data on a set of selected regions, as described in the 'Materials and Methods' section. Regression analysis of PIC component binding in each med17 mutant versus WT was systematically performed. Genome-wide Mediator occupancy was analyzed for the Med15 Mediator subunit. It was not possible to obtain good quality ChIP-seq results for the Med5 Mediator tail module subunit or the Med6 and Med8 Mediator head module subunits (see 'Materials and Methods' section).
ACKNOWLEDGEMENTS We thank  F. J. Asturias  for CA001 strain,  C. Thermes ,  E. Van Dijk  and  Y. Jaszczyszyn  for performing the high throughput-sequencing of ChIP samples, the  SPI (CEA/Saclay)  for monoclonal antibodies and  L. Kuras  for critical reading of the manuscript. This work has benefited from the facilities and expertise of the high-throughput sequencing and the  SICaPS mass spectrometry platforms of IMAGIF (Centre de Recherche de Gif , www. imagif. cnrs. fr).
FUNDING Agence Nationale de la Recherche  [ ANR 11 BSV8 020 01 ,  ANR-14-CE10-0012-01 ];  Fondation ARC  [SL 2201130607079];  Fondation ARC  [ DOC20130606697  to F. E. ]. Funding for open access charge: Fondation ARC [SL 2201130607079].
Nutrient Supply Data Estimates of country-level dietary micronutrient supplies in Africa were obtained from recent work by Joy et al. which estimated dietary micronutrient supplies and deficiencies at national levels across Africa. In their work, they estimated mean national nutrient supply per capita (all ages and both genders combined) by integrating national-level food balance sheets (FBSs), which represent aggregate food supply for 92 edible food items at the retail level and food composition databases. Full details of their methodology are published, and all data extracts included in the present study were obtained from online supplementary tables  [16]. In brief, they sourced FBSs for 2009 from the United Nations Food and Agriculture Organization  [17]. Nutrient compositions were then assigned to each food item using, depending on the country's location, one of three regional food composition databases.
Those three databases were developed using best-fit estimates from 16 sources. Per capita supplies of seven nutrients were estimated overall and by six food sources, for Ca, copper (Cu), iron (Fe), I, magnesium (Mg), Se and Zn. Additionally, we extracted the national estimates of total dietary supplies of energy (kcal) and phytate from that study. Phytate is the principal form of phosphorus storage in plants and is found at high concentrations in cereal and legume seeds. It can chelate with elements including Fe, Mg and Zn, limiting their bioavailability in the human gut. Using this FBS methodology, dietary nutrient supplies as proxies for nutrient intake were available for 46 African countries (listed in Table  1 ). National nutrient supplies per capita were also compared to nutrient requirements.
Cancer Incidence Data Cancer incidence data were sourced from GLOBOCAN. Country-specific estimates of the number of incident EC cases (ICD-10 C15) in 2012 and corresponding population counts from UN Population Divisions 2012 estimates (United Nations 2013) were obtained from GLOBOCAN, extracted by sex and five-year age group  [1]. GLOBOCAN 2012 includes a quality indicator describing the data quality for each country's incidence estimates. Of the 46 countries with micronutrient data, we excluded 14 countries (indicated in the footnotes to Table  1 ) for which GLOBOCAN estimates were solely based on rates in neighbouring countries, i. e. no data were available in the country itself (as some countries have no cancer registries). For the countries with estimated new cases of EC in 2012, the estimates refer to all histological subtypes of this cancer, but EC is predominantly ESCC in this region.
Covariate Information on Confounders National sex-specific daily tobacco smoking prevalence for adults aged 15+ years for 2012 were obtained from a worldwide study which modelled nationally-representative smoking prevalence data from 1980-2012  [22]. Country-level gender-specific estimates of total alcohol consumption per capita at ages 15 years and older in 2008-2010 (total consumption of recorded and unrecorded litres of pure alcohol per capita per year) were obtained from WHO  [23]. Regional smoking and tobacco prevalence were calculated as averages of country specific prevalence, weighted by the corresponding gender-specific population size.
56 × 10 9 cm/s. The impact of the newly measured masses is shown in Fig. 5  and seen to give rise to an abundance peak that is now shifted by one unit; i. e. , the peak location is now at A = 128 and A = 129. Interestingly, despite the fact that the present distribution results from a mass-weighted average of hundreds of trajectories, the modification of only three masses still has an impact on the abundance ratio in the corresponding region. This property is linked to the fact that the masses affect directly the top of the A = 130 peak. In conclusion, the masses of 129-131 Cd were determined with high precision using the Penning-trap mass spectrometer ISOLTRAP. The new masses show a significant reduction of the N = 82 shell gap for Z < 50. The new data provide additional constraints for nuclear theory, considering the diverging predictions of mass models concerning the N = 82 empirical shell gap for Z < 50.
Acknowledgments The authors thank  G. Audi ,  CSNSM-IN2P3-CNRS , for the fruitful discussion in the process of data analysis. We thank the  ISOLDE technical group  and the  ISOLDE Collaboration  for their support. We acknowledge support by the  BMBF  ( 05P12HGCI1 ,  05P12HGFNE ,  05P15HGCIA , and  05P09ODCIA ),  Nuclear Astrophysics Virtual Institute (NAVI) of the Helmholtz Association, Helmholtz-CAS Joint Research Group  ( HCJRG-108 ), the  Max-Planck Society , the European Union 7th framework through ENSAR (Contract No. 262010 ), the  French IN2P3 , the  Helmholtz Alliance Program , Contract No. HA216/ EMMI , by the  STFC  under Grants No. ST/L005743/1  and No. ST/L005816/1. D. A. acknowledges support by the  IMPRS-PTFS. S. Goriely acknowledges financial support from  FRS-FNRS (Belgium).
Excitation laser lines and filters used for each fluorophore are summarized in Table  S1. Data were analyzed using FlowJo software (Tree Star). For colony formation assays, sorted cells were plated on g-irradiated MEFs in 12-well plates at 1. 0-3. 0 3 10 3 cells per well. Nanog-GFP + colonies were quantified 10 days after sorting. For time course analysis of the sorted subpopulation, the cells were plated on g-irradiated MEFs in 48-well plates at 3 3 10 4 cells per well. In both cases, cells were cultured in reprogramming medium after sorting.
Global Gene Expression Analysis Multiplexed RNA sequencing was performed as described previously using 10 ng RNA of each sorted subpopulation, and quality control and alignment to the mouse reference genome (NCBI37. 1/mm9) were performed using the STRT method pipeline as previously described  (Islam et al. , 2011). The heatmaps were generated using the average of replicates of variance-stabilizing transformed (VST) gene expression read counts (generated using the DESeq package in R), and mean-centered per gene. Color code black (0. 00) means that the expression level is equal to the mean expression levels of all samples (from MEFs to WT ESCs) of the gene. PCA was performed in R and plotted with the scatter-plot3d library  (Ligges and Maechler, 2003). Cluster overlaps were plotted using a Circos-generated chord diagram  (Krzywinski, et al.
ACKNOWLEDGMENTS We thank  F. Rossi  and  C. Cryer  for assistance with flow cytometry and  D. Kaemena ,  M. Foronda ,  T. Ruetz ,  L. Tosti , and  A. Tsakiridis  for discussions and comments on the manuscript. We also thank  L. Robertson  and  J. Rennie  for technical assistance and the  Biomed unit  staff for mouse husbandry. This work was supported by  European Research Council (ERC)  grants  ROADTOIPS  (no. 261075  to K. K. ) and BRAINCELL (no. 261063  to S. L. ), the  Anne Rowling Regenerative Neurology Clinic , and the  Swedish Research Council (STARGET). We acknowledge the  Medical Research Council  for their support. S. S. acknowledges financial support for this project from the  SystemsX. chinitiative, evaluated by the  Swiss National Science Foundation.
0001) and were on the order of a 13% to 76% relative change. There were also changes in Ees sb of borderline significance, on the order of 5. 8% (P=0. 052). These data suggest that CRT results in the most substantive changes in measures indicative of LV size, primarily reflected by volumetric measures: V 0 , LVEDV, and LVESV. There were no significant changes in afterload, as assessed by Ea, or ventricular-arterial coupling, as assessed by Ea/Ees sb.
Global School-Based Student Health Survey Of the ten PICTs conducting GSHS between 2010 and 2013, seven employed a two-stage sampling design to obtain a representative sample of students. Schools were selected by probability proportional to size and then classes within these schools were selected randomly. All students in these classes were eligible to participate. In the Cook Islands, Nauru and Niue, a census was used to obtain data on the target student population. Local policies and practices govern whether parental approval is required for students to participate in GSHS. Parents are usually notified of the survey in writing and permission requested as needed  [23]. Students aged 13-17 years in the selected classes complete a selfadministered, anonymous questionnaire which includes questions on demographics, diet and physical activity.
Survey staff measure participants' height and weight beforehand and provide these results in writing to each individual for them to transfer to their computerscannable answer sheet. Data are weighted to account for sampling design, population distribution by grade and sex, and non-response. A response rate of over 60 % is required for results to be weighted and therefore generalized to the target population  [24]. The surveys included in this analysis had overall response rates of 72 % or higher. We extracted data from factsheets of GSHS which provided results for the subset of the survey population aged  13-15 years [25-34]. Youth Risk Behavior Surveillance System YRBSS surveys have been conducted at least twice in five USAPIs between 1999 and 2013. Local polilcies guide procedures for gaining parental permission and may include obtaining written consent from parents for students to take part in the survey  [35].
The sampling design and analysis of YRBSS are similar to GSHS  [24, 35]. Generally, in USAPIs apart from Guam, surveys were designed to include all members of the target population. In YRBSS, students in grades 9-12 (approximately 14-18 years) complete an anonymous questionnaire on a range of risk and protective behaviours. Height and weight are selfreported. A response rate of 60 % or more is required for results to be weighted  [35]. We extracted results primarily from CDC's database, Youth Online  [22]. For CNMI, we also used results published by Lippe et al. [36]. For each USAPI, we examined the most recent year for which sexspecific weighted data were available. We also analysed trends over time in overweight and obesity prevalence.
Prevalence of daily consumption was lowest in Kiribati and highest in Niue where 74 % of males drank soft drinks every day. Prevalence was often similar between the sexes, though notably higher in females in the Cook Islands (64 %) and Tuvalu (55 %). The proportion of students in grades 9-12 who drank soda at least once per day in the past week varied in the Republic of the Marshall Islands. Overweight was defined as ≥85th and < the 95th percentile for body mass index (BMI) by age and sex. Obesity was defined as ≥95th percentile for BMI for age and sex. Height and weight were self-reported. Confidence intervals were reported for Guam and American Samoa (1999) only as other surveys in American Samoa, CNMI, Palau and RMI were designed to include all members of the target student population three USAPIs for which data were available.
Strengths and limitations By collating the most recent available and comparable data from GSHS and YRBSS across 15 PICTs, this work fills a critical gap in evidence on overweight, obesity and their associated risk factors in Pacific adolescents. The analysis presented is based on the information provided from the data sources, in addition to resource guides on the general methodology of these surveys. Although this work provides an important regional perspective on adolescent obesity, our analysis is limited due to incomplete coverage of the Pacific; critically, it does not include representative data for the most populous nation, Papua New Guinea. In addition, the prevalence of obesity and associated risk factors may have changed since the surveys used for our analysis were undertaken. Of note, more recent sex-specific YRBSS results from CNMI, RMI, Palau and American Samoa were not available through Youth Online.
Acknowledgements We are grateful to  Dr Colin Tukuitonga  and  Dr Paula Vivili  who contributed to the concept for this article. We also thank  Dr Yvan Souarès  for his guidance with this work, and  Dr Terry Quirke  for review of a first version of this article. We gratefully acknowledge the contribution of national health staff in the Pacific who undertook the surveys that were used to inform this paper. We also appreciate the contribution of the  World Health Organization  and the  Centers for Disease Control and Prevention  to this process.
One sample (T1) displayed only a slow-migrating fragment. These results pointed to the existence of insertion(s) in this exon. This was confirmed through exon-3 amplification with other pairs of primers. We performed a similar analysis using the cDNAs from 4 cryopreserved tumors (T13-T16, for which high-quality mRNA was available) and again the insertions were apparent, in agreement with the results obtained with the corresponding gDNAs (Fig. 1A ). An analysis of gDNA extracted from the peritumoral tissue, available only for two of the samples bearing the insertions, formally proved the somatic status of these two mutations (Fig. 1B ). Sanger sequencing of the isolated DNA bands showed the presence of 10 in-frame tandem duplications, which had never been reported either in the literature or in the databases (Fig.
The In-frame Duplications Alter the Pleckstrin Homology Domain of AKT1 and Lead to Oncoprotein Activation The tandem duplications described here alter the PHD of AKT1  (Gibson et al. , 1994). The PHD binds to phosphatidylinositol-di/ trisphosphates (PIP2 and PIP3) from the plasma membrane, which are produced by activated PI3K  (Franke et al. , 1997). This leads to the translocation of AKT to the plasmalemma. In such conditions, phosphoinositide-dependent kinases (among others) phosphorylate AKT1 on T308, leading to its partial activation. Full activation is achieved upon phosphorylation of S473  (Warfel et al. , 2011; Mahajan and Mahajan, 2012). On structural grounds, the PHD involves two main beta sheets (Protein DataBase structures 1H10, 3O96 and 4EJN). The tandem duplications described here involve the 6th beta strand, according to the ribbon model displayed in Fig.
Such a structural defect might alter the interaction with the plasma membrane and/or with the kinase domain (KD). Webb and Sali, 2014). We propose three main types of spatial arrangements, according to the insertions. These predictions do not take into account the presence of the rest of the protein. Structures (PDB: 3O96 and 4EJN) including the PHD and KD domains lack the segment linking both domains, which renders difficult the construction of realistic models. Only X-ray crystallography of both PHD and KD will allow us to work out the impact of the duplications on protein structure. Mutations in AKT1 at the PHD-KD interface, as is the case here, that weaken their interaction have been previously reported in human cancers  (Parikh et al. , 2012). Such altered interactions in our mutants could explain the dramatic tropism for the plasmalemma and the concomitant increase of phosphorylation.
Does were fed balanced pelleted diets and divided in two feeding groups which were homogeneously formed considering similar body weight, parity order and status of production (lactating, non-lactating). The first group (n=51) was fed a commercial diet (C), whereas in the other group (n=52) the animals received the same diet supplemented with 300 mg/kg of Digestarom ® (D). Experimental diets were available ad libitum and were isoprotein, isoenergy and had similar chemical composition (Table  1 ). Rabbit does were weighed at kindling and kindling rate was calculated as kindling/AI (%). Litter size data (number of kits born total, alive, stillborn) were recorded at the day of kindling. During the experiment, litter size and litter weight were registered after nursing at 7, 14, 21 days of age, and the individual weight of kits was calculated (litter weight/litter size).
Statistical analysis Data were analysed using the General Linear Model Procedures of the SAS 9. 1 statistical analysis software for Windows  (SAS, 2004). All does and kits performances were subjected to a one-way ANOVA in which experimental diets (C, D) were a fixed effect and the number of kindlings was considered as random effect. A Chi squared test was performed to evaluate kindling rate and mortality. Differences were considered significant when P<0. 05.
Ten trees were sampled in the high-density stand and 13 trees were sampled in the low-density stand. These trees had complete series of Q s data available for two consecutive growing seasons:  2004-2005 and 2005-2006. As has been well described in  Licata et al. (2008) , these growing seasons may be considered dry (70 mm) and wet (225 mm) respectively, representing ±1 standard error of the mean precipitation value from November to April, according to a 23 year-long climate time series obtained from a meteorological station belonging to the National Meteorological Service of Argentina located 70 km south of the study site. The tree-rings are identified in this study with the first calendar year corresponding to the period of wood formation (i. e. , the growth ring formed in the Southern Hemisphere growing season 2004-2005 is named 2004).
Environmental variables: soil water content and potential evapotranspiration (PET) Soil water content was continuously measured in the study plots during 2004 and 2005 (dry and wet years, respectively) with multiple sensors of frequency domain capacitance probes (Sentek EnviroSMART, Sentek Pty Ltd. , Adelaide, Australia)  (Licata et al. , 2008). Soil water content data were recorded every 15 s (sec. ), and 30 min (min. ) averages were stored in a CR10X Campbell Scientific datalogger. The Sentek measurement system employs long probes, which are inserted into 5. 5 cm diameter PVC casings. The casings, in turn, are installed in holes augured into the soil. Probes were 2 m long, with six sensors per probe at 10, 20, 40, 80, 140, and 180 cm deep. From this data, daily average soil water content was determined for each sensor (four probes in each canopy treatment in 2004 and three probes in each treatment in 2005).
, 1998)  for daily climatic data. ET ref represents the maximum PET of a hypothetical reference crop with no water deficiency, growing under the same meteorological conditions as measured in the field site. Meteorological data were acquired from a meteorological station (Campbell Scientific; Logan, UT, USA) installed seven km from the study plots. As mentioned above, climatic data (23 years of monthly precipitation averages) were obtained from a meteorological station belonging to the National Meteorological Service of Argentina located at the Bariloche airport (70 km south of the study site).
A ring of thermal and radiation insulation (Mexpol Ò , 9 mm) was placed around the stems, covering the sensors and at least 20 cm above and below them, to avoid any thermal gradient effects on the stems. Sensor output was measured every 15 s and averaged every 30 min with a Campbell CR10X data-logger and an AM416 multiplexer. The data were analyzed on a daily time-step and were transformed into sapflow density on a sapwood area basis (Q s ) following  Granier (1987). Daily transpiration estimated from these data, taking into account the decrease in sapflow density along the wood radial profile, can be consulted in  Licata et al. (2008). For the purpose of this study, the maximum sapflow density of the radial profile, that is, the Q s of the outermost part of the stem xylem, was used to analyze the relationship of plant water status and wood microdensity (see below).