dataesr/scientific-paragraphs-categorization huggingface dataset:
An email is sent to the CDS documentalists who correct, if necessary, the bibliographical data every morning. Furthermore, each reference has an associated status that indicates that work has been done on it. The status generally goes with a detailed comment that indicates what has already been done. At the end of the week the program counts the total of every status and makes a comparison with the file containing the status of the last week. It reports to documentalists the number of status added, removed and the modifications of comments. When data are modified in SIMBAD, tests allow verification of links validity and their correction if needed.
Conclusion Receiving all of these data from the publishers allows us to be more exhaustive and more efficient. Bibliographical data go through a lot of steps from the publishers to SIMBAD. These processes and verifications are essential to maintain the quality and coherence of the database. Data are checked automatically or manually until their integration in SIMBAD which makes mistakes rare, moreover permanent checks ensure the correctness over time. Improvements are in progress to homogenize the database with the new abstract, keywords and DOI added to SIMBAD. Developments for table extraction continues with the objective to process more journals and return better results.
One-legged glycogen supercompensation regime in man The study was approved by the regional ethics committee in Denmark (Journal number: H-4-2013-071) and performed in accordance with the Declarations of Helsinki II. Each subject gave written informed consent before participating. Nine healthy male subjects (age, 26 AE 3 years; BMI, 23. 5 AE 1. 7 kg/m 2 ; VO 2 peak, 45 AE 4 ml O 2 /min/kg; data presented as means AE SD) underwent a glycogen supercompensation regime. The study design is illustrated in Figure  1  and a detailed description of preclinical investigation of the subjects and the experimental design is provided in Supplemental I. The subjects were familiarized to the one-legged knee extensor model at light intensity prior to the testing. The working leg was chosen randomly in order to avoid possible confounding effects of leg dominance.
Proteomic analyses of human muscle biopsies Muscle biopsies for proteomic analyses were processed and analyzed as previously described  [34]. A detailed description can be found in Supplemental I. For MS data repository and the complete data set, see Supplemental III. 1 : Study design for one-legged glycogen supercompensation in man. Nine lean and healthy male subjects underwent a one-legged glycogen supercompensation regime. Muscle glycogen content was reduced (day 1), normalized (day 2), and supercompensated (day 5) in one leg while remaining unchanged in the resting control leg. On average the subjects exercised for 2 1 / 2 h. Througout the 5 days the subjects consumed a eucaloric carbohydrate-rich diet. Muscle insulin action was evaluated under these three different situations by euglycemic hyperinsulinemic clamps (EH Clamps) and femoral catheterization in combination with measurement of femoral leg blood flow enabled to calculate insulin-stimulated leg glucose uptake.
Muscle AMPK activity is elevated for 5 days following a single bout of exercise Given that AMPK contains a glycogen-binding domain and serves as a cellular fuel-sensor, we evaluated regulation of muscle AMPK throughout the human glycogen supercompensation regime. A temporal and heterotrimeric-specific regulation of AMPK activity was evident in muscle (Figure  3A,B  and E ). Thus, AMPK a2-containing complexes were highly activated in recovery from exercise (day 1) (p < 0. 05) and reversed to resting levels the subsequent days (day 2 and 5) (Figure  3AeB ). This regulation coincided with enhanced insulinstimulated muscle glucose uptake (Figure  2B ) and elevated phosphorylation at Ser704 and Ser341 of the AMPK downstream target TBC1D4 (day 1) (p < 0. 001) (Figure  3CeD ). In accordance with previous studies demonstrating that the proximal insulin-signaling cascade in human muscle remains unaffected by prior exercise  [33,39e41] , we observed that Akt phosphorylation at Ser308 and Thr473 increased similarly in both legs in response to insulin (data not shown).
Muscle glycogen content in quadriceps muscle was measured in the basal state and 5 h post exercise with glucose gavage (2 g/kg body wt) given immediately after 1 1 / 2 h exercise and again following 1 h recovery. ### p 0. 001 for different from corresponding resting value. y p 0. 005 and yy p 0. 01 for effect of genotype. Data are presented as means AE SEM (n ¼ 4e8). exercised and rested muscle (Fig. S3 ). In contrast, fractional enzyme activity of GS was markedly elevated in the prior exercised muscle (day 1) (p < 0. 001) and remained elevated the following days (p < 0. 01) even though muscle glycogen content was normalized to resting levels or supercompensated (Figure  5A ). In accordance, phosphorylation of key inhibitory residues on GS was markedly reduced by exercise (day 1) (p < 0. 001) and remained lower the day after exercise (day 2) (p < 0.
Muscle biopsies were obtained before (basal state) and under insulin-stimulated conditions (following 120 min insulin infusion). Proteomic analyses was performed on basal biopsies obtained at day 1, 2, and 5 (n ¼ 5). The exercised leg is presented relative to the rested control leg as log2 ratio. Circle size indicates the magnitude of increase/decrease and significant p-value is illustrated by black circles (D). Basal and insulin-stimulated muscle lysates were investigated for protein expression of GLUT1, GLUT4, HKI, and HKII by use of immunoblotting (EeH). Data are expressed as means AE SEM (n ¼ 8e9). Western blotting data are given as arbitrary units (AU). y p 0. 05, yy p 0. 01 and yyy p 0. 001 for effect of leg. ¤¤ p 0. 01 and ¤¤¤ p 0. 001 for significant different from day 1. Main effect is indicated by horizontal line.
Questionnaire and Variables The detailed questionnaire was distributed randomly by interviewers who received a thorough training prior to the start of the data collection to ensure adequacy and standardization of the process. A pretested self-administered questionnaire, adapted to local Arabic language (the native language in Lebanon) adapted from the standardized and validated chronic respiratory disease questionnaire of the American Thoracic Society was used. The standardized ISAAC questionnaire was used, after translation into Arabic and back translation into English to ensure accuracy of the questions. We calculated the reliability of the scale to assess the quality of our data. More details about the methodology have been published previously  [13] [14] [15] [16] [17] [18]. The questionnaire assessed the sociodemographic characteristics, including age, gender, region, number of rooms and the number of persons living in the house, the levels of education for both parents, the family history of asthma, and other known risk factors of allergic disease (the heating system used inside the house, child's history of recurrent otitis, humidity inside the house, if the child went to a nursery, etc.
Statistical Analysis Data analysis was performed using SPSS software, version 23. Percentages were shown for qualitative variables, while means and standard deviation were given for quantitative variables. Two-sided statistical tests were used to compare between-group percentages and Student t test for quantitative variables of normal distribution and homogeneous variances. Moreover, a multivariable backward logistic regression was applied taking healthy children versus children with allergic disease as the dependent variable, using variables that showed a p < 0. 2 in the bivariate analysis; potential confounders were eliminated only if p > 0. 2, in order to protect against residual confounding. A p value < 0. 05 was considered significant.
We follow here the original character description and scorings as in  Denton and O'Neill (1995) , in order to avoid confusion with scorings of this character in previous works  (Nydam and Cifelli, 2002; Nydam et al. , 2007). (82) Quadrate, pterygoid lappet  (Estes et al. , 1988: 37; Conrad, 2008: 160)      (86) Parietal-supraoccipital contact  (Lee & Scanlon, 2002: 136; modified from Gauthier et al. , 2012: 96 ): (0) absent; (1) dorsoventral parasagittal abutment. Comments: We follow usage of this character according to  Gauthier et al. (2012). Gauthier et al. 's (2012)  matrix presented three additional characters that were excluded because they were non-informative in our dataset: states 1 (parietal overlaps supraoccipital on midline), 2 ([parietal] abuts supraoccipital on midline) and 4 (supraoccipital around processus ascendens tectum synoticum forms stout, flat-topped pedicle that abuts parietal posteroventromedially).
On the other hand,  Gauthier et al. (2012)  scored Heloderma suspectum as state 1 (reduced), but analyzing the preserved specimen in our collection we observed it as state 2 (absent). Also, the authors scored Pholidobolus montium as state 0, but we consider it as state 1. (1) contact at apex of alar process; (2) extensive conformable contact, with parietal overlapping prootic laterally throughout length. Comments:  Gauthier et al. 's (2012)  matrix presented four different states for this character. We excluded the fourth state 3 (discrete ventral process of parietal overlaps prootic alar process laterally) from  Gauthier et al. 's (2012)  original character description, given that it was non-informative in our dataset. Also, we disagree with the authors' scoring for Callopistes maculatus as state 0, given that this taxon actually retains the parietal-prootic contact, and thus is considered as state 1 (observed in the dry specimen).
(91) Vidian canal caudal opening  (Estes et al. , 1988: 53; Lee, 1997: 38; Conrad, 2008: 146; Brizuela, 2010: 70; modified from Gauthier et al. , 2012: 337 ): (0) within basisphenoid; (  1 ) anterior margin at basisphenoid-prootic suture; (2) the dibamidamphisbaenian condition. Comments: We follow usage and scorings of this character according to  Gauthier et al. (2012). In their matrix, the authors presented a third state 2 (entirely within prootic), which was excluded from our analysis given that it was non-informative in our dataset. (92) Medial aperture of the recessus scala tympani (MARST)  (Gauthier et al. , 2012: 344) : (0) between basioccipital and otoccipital (opisthotic); (  1 ) entirely in otoccipital (opisthotic). (93) Hypoglossal (XII) foramina exit(s) relative to vagus (X-XI) foramen on external surface of braincase  (Lee, 1998: 69; Conrad, 2008: 153; Gauthier et al.
, 1988: 77; Gauthier et al. , 2012: 409)   Comments: We follow usage of this character according to  Rieppel and Zaher (2000)  and scorings according to  Conrad (2008). We consider  Rieppel and Zaher's (2000)  character state 3 (teeth ankylosed to the rim of a shallow socket that is homologous to the interdental ridge) and  Conrad's (2008)  character state 4 (subacrodont) to be noninformative in our dataset, and thus they were excluded from our analysis. Comments: This character was redefined from  Estes et al. (1988)  by previous authors, and so we follow usage of this character according to new character definitions  (Denton and O'Neill, 1995; Nydam and Cifelli, 2002; Nydam et al. , 2007). In our analysis, scoring for this character was only possible in species that present pleurodont or modified pleurodont implantation (see character 124 above), and so taxa with different tooth implatation were scored (?).
, 2012: 412 ): (0) similar; (1) markedly smaller. Comments: We follow usage of this character according to  Conrad (2008: 223). The third state of the author's description 2 (absent) is non-informative in our dataset and thus was excluded from our analysis. (131) Premaxillary teeth, cusps  (Denton & O'Neill, 1995: 28; Nydam & Cifelli, 2002a: 28; Nydam et al. , 2007: 28 ): (0) simple, unicuspid; (1) complex, bicuspid, tricuspid. (138) Anterior maxillary teeth  (Denton & O'Neill, 1995: 29; Nydam & Cifelli, 2002a: 29; Nydam et al. , 2007: 29; Brizuela, 2010: 122 ): (0) simple, unicuspid; (1) complex, bicuspid, tricuspid. (142) Longitudinally striate posterior teeth  (Denton & O'Neill, 1995: 30; Nydam & Cifelli, 2002a: 30; Nydam et al. , 2007: 30; Conrad, 2008: 219; Brizuela, 2010: 124 ): (0) absent; (1) present.
Diffraction data were collected at 100 K on beamline 14. 1 of the BESSY II storage ring (Berlin, Germany) and were processed by the program XDS  (27). The structure was determined by molecular replacement with Phaser (28) using the RecA domains and domain 1C of UPF1 2 CH as a search model, while domain 1B was built de novo. Iterative model building and refinement were performed using Coot and Phenix, respectively  (29, 30). The final model was validated with the program Molprobity  (31).
Fluorescence anisotropy assay Fluorescence anisotropy measurements were performed with a 5 -6-carboxy-fluorescein (6-FAM)-labeled 26-mer RNA at 25 • C in 40 l-reactions in a Victor plate reader (PerkinElmer). The RNA was dissolved to a concentration of 5 nM and incubated with the UPF1 proteins at different concentrations in binding buffer (20 mM HEPES pH 7. 5, 150 mM NaCl, 1 mM MgCl 2 , 5% glycerol and 2 mM DTT). Where indicated, ATP was added to a final concentration of 10 M. The excitation and emission wavelengths were 485 and 535 nm, respectively and each titration point was measured three times. The data were analyzed by nonlinear regression fitting as described in  (32)  using GraphPad Prism (GraphPad Software, Inc. ). Unpaired t-test derived P values were calculated to determine the significance of the differences in K d between UPF1 1 and UPF1 2 or between UPF1 1 CH and UPF1 2 CH, in the absence and presence of ATP.
For measurements in the presence of RNA, a 1. 5-fold molar excess of U 15 RNA was added to the protein solution and incubated at room temperature for at least 30 min. All other steps were carried out in a manner identical to the measurements in the absence of RNA. At least six replicates were performed in every case. Data were visualized using the software Pro-Data Viewer. Data analysis is described in detail in the Supplementary Information (Supplementary Figure  S1 ). ------------------------------------------------------------------------------------------ UPF1 loop. The insertion of 11 residues within the regulatory loop of UPF1 1 is indicated by (X) 11. (B) X-ray crystal structures of apo-(left panel) and AMPPNP-bound UPF1 2 CH (middle panel) and of UPF1 2 CH in its transition state, bound to RNA and ADP:AlF 4 -(right panel).
The domains are colored according to the schematic in (A). RNA and nucleotides are shown as black sticks. The 11-amino acid regulatory loop in domain 1B (colored blue) occupies part of the RNA-binding surface in the apo-and AMPPNP-bound structures, but is disordered in the transition-state structure. This and all other structure figures have been generated using PyMOL (http://www. pymol. org). (C) RNA-dependent ATPase assay of UPF1 1 , UPF1 2 , UPF1 2 CH and UPF1 loop performed using an enzyme-coupled phosphate-detection assay. The data points and error bars represent mean values and standard deviations from three experiments, respectively. The symbols ns, ** and *** denote unpaired t-test derived P values of >0. 05, 0. 001 and <0. 001 respectively. Enhancement of ATPase activity upon deletion of the CH domain is shown for comparison.
RT-PCR RNA was extracted from ∼1 × 10 6 cells using RNATri (Bio&Sell) and 0. 5 g of total RNA was used for reverse transcription with the UPF1 reverse primer (sequence given below). To detect the mRNA corresponding to the two isoforms of human UPF1, we designed primers specific to sequences in exons 7 and 8, which flank the alternative 5splice site and, upon amplification, would generate products of 166 and 133 bp for human UPF1 1 and UPF1 2 isoforms, respectively. The primer sequences are as follows: forward 5 -GGGACCTGGGCCTTAACAAGAAGAGA-3 and reverse 5 -ATCCCTTTCCACAGGGGCGCAAGGT-3. Plasmids expressing the human UPF1 1 CH and UPF1 2 CH proteins were used as positive controls. For quantification of mRNA levels of the two isoforms low-cycle PCRs were performed with the 32 P-labeled forward primer (sequence given above), products were resolved by denaturing-PAGE and analyzed using a Phosphoimager and the ImageQuantTL software (GE Life Sciences).
ACKNOWLEDGEMENTS We thank  Elena Conti  ( MPI of Biochemistry, Martinsried ) for support at the initial stages of the project and gratefully acknowledge  Florian Heyd  and  Markus Wahl  ( Freie Universität Berlin ) as well as members of our laboratory for helpful discussions. We are especially grateful to  Agnieszka Pietrzyk  and  Karine Santos  for sharing their expertise on stopped-flow experiments and data analysis,  Eva Absmeier  and  Christian Freund  for help with fluorescence anisotropy assays,  Olga Herdt  and  Alexander Neumann  for analysis of mRNA sequences and RNA-seq data and  Bernhard Loll  for assistance with X-ray data collection at  BESSY II (Berlin, Germany ). Access to BL14. 1 of  BESSY II  was obtained via the  Joint Berlin MX laboratory. The mRNA samples from different mouse tissues were a generous gift from  Astrid-Solveig Schultz  and  Florian Heyd.
We thank  Varun Bhaskar ,  Atlanta Cook ,  Felix Halbach  and  Karine Santos  for critically reading the manuscript. Author contributions: M. G. and S. C. purified the proteins used in this study, performed crystallization trials and determined the structure. M. G. , F. B. , J. K. and F. F. performed the biochemical experiments. M. G. and V. D. M. carried out the RT-PCR analyses of the UPF1 isoforms. J. K and S. R. performed the single molecule nucleic acid unwinding assays and were supervised by H. L. H. and V. C. S. C. conceptualized the study and wrote the manuscript with input from all the authors. FUNDING  Deutsche Forschungsgemeinschaft  [ CH1245/2-1  to S. C. ];  Investissements d'Avenir  [ ANR-10-LABX-54   MEMO-LIFE  and  ANR-10-IDEX-0001-02 PSL* Research University  to J. K. and H.
L. H. ];  Centre National de la Recherche Scientifique , the  Ecole Normale Supérieure ;  Agence Nationale de la Recherche  [ ANR-13-BSV8-0023  to H. L. H. and  ANR-14-CE10-0014  to H. L. H. and V. C. ];  Fondation ARC pour la recherche sur le cancer  (to J. K. ); Max Nucleic Acids Research, 2018, Vol. 46, No. 5 2659 Planck Gesellschaft (to F. B. ). Funding for open access charge:  Deutsche Forschungsgemeinschaft  [ CH1245/2-1 ];  Freie Universität Berlin.
MATERIALS AND METHODS gRNA Design and Plasmid Construction gRNAs were designed using the ZiFiT Targeter 4. 2 (http://zifit. partners. org) online software. Five gRNA (N1-N5) sequences targeting COL7A1 (Table  S1 ) were cloned into the plasmid MLM3636 (Addgene 43860) according to the available guidelines. The activity of gRNAs was tested using the plasmid PX165 encoding for the human codon-optimized Cas9 nuclease from Streptococcus pyogenes (SpCas9) (Addgene 48137). Selected gRNAs displaying activity in HEK293T cells were cloned into the plasmid lentiCRISPR_v2 (Addgene 52961) according to the available guidelines to efficiently transduce RDEB-Ks and RDEB-Fs. The LV-Donor lentiviral vector, used for gene-targeting experiments, was described previously. 16 ntiviral Vector Production and Titration gRNAs and the Donor template were delivered as IDLVs, pseudotyped with the vesicular stomatitis virus G protein (VSV-G) envelope glycoprotein.
Untreated cells were used as controls. 200 ng purified PCR products were denatured, digested with the nucleotidemismatch-sensitive Cel1 endonuclease, and analyzed on 1. 5% agarose gel using ImageLab (Bio-Rad) software. The intensities of the bands were quantified by ImageJ. The percentage of NHEJ was calculated using the formula 100 Â (1 À (1 À fraction cleaved) 1/2 ), where the fraction cleaved is the ratio of the intensity of the cleaved bands (digested bands) over the cleaved and un-cleaved bands for each experimental setting. In parallel, PCR products amplified from RDEB-Ks and RDEB-Fs treated with IDLVs encoding for the gRNA N1 were sequenced by Sanger and analyzed by the TIDE web tool (https://tide. nki. nl), as initially described by Brinkman and colleagues. 65.
After cycling, the 96-well plate was immediately transferred into the Bio-Rad QX-100 Droplet Reader, where flow cytometric analysis determined the fraction of PCR-positive droplets (blue and green dots) versus the number of PCR-negative (gray dots) droplets in the sample. Data were analyzed by QuantaSoft Software (Bio-Rad) using the RED (rare events detection) option. The concentration of target versus reference DNA was automatically determined and corrected for Poisson distribution. All error bars were generated by the software and represent 95% confidence interval. To evaluate the efficiency of COL7A1 editing in transduced RDEB cells after CRISPR/Cas9-mediated HDR, 50 ng genomic DNA of corresponding samples was subjected to ddPCR. The assay was performed using primers and probes complementary to the corrected or the mutated sequence in exon 2 of COL7A1 (custom design).
b-actin immunodetection served as a loading control. Signals were revealed with ECL-plus reagent (Thermo Scientific) using ImageLab software (Bio-Rad). For the detection of secreted C7, keratinocytes were grown for 48 hr in the presence of 20 ng/mL transforming growth factor b2 and 50 mg/mL ascorbic acid in a serum-free keratinocyte growth medium. The medium was collected, precipitated, and analyzed using LH7. 2 antibody as described above.
IncuCyte Live-Cell Imaging Gene-corrected fibroblast morphology and proliferation were investigated using the IncuCyte live-cell imaging device available at Imagine Institute. Briefly, primary NHFs from two different donors, RDEB-Fs treated with LV-CRISPR-N1 and LV-Donor, RDEB-Fs treated only with LV-Donor, and untreated RDEB-Fs were seeded at 10 4 cells/ well in 12-well plates and monitored during 8 days for confluence and proliferation. Cells were seeded in triplicates. Five independent regions were scanned for each well every 6 hr during 8 days with the live-cell-imaging system (phase-contrast, objective 4Â). Data were analyzed using the IncuCyte S3 basic analyzer software.
Participants We included participants from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. The aim of this study was to discover novel diagnostic and prognostic markers for pre-dementia AD, by making use of existing data and samples  [13]. The EMIF-AD MBD study pooled data of 494 CN, 526 MCI and 201 AD-dementia participants from three multicentre and eight single-centre studies. Inclusion criteria were: presence of normal cognition, MCI or a clinical diagnosis of AD-type dementia; availability of data on amyloid pathology, measured in CSF or on PET; age above 50 years; availability of MRI scans, plasma, DNA or CSF samples (at least two of the modalities); and absence of major neurological, psychiatric or somatic disorders that could cause cognitive impairment.
Clinical and cognitive data From all parent cohorts, clinical information and neuropsychological tests were collected centrally, harmonized, pooled and stored in an online data platform as previously described  [13]. In short, all parent cohorts administered the Mini-Mental State Examination (MMSE), and performed neuropsychological testing covering various cognitive domains, although the tests used varied across the different cohorts. For the cognitive domains memory, language, attention, executive functioning and visuo-construction, one priority test was selected from each cohort (Additional file 1: Table  S1 ) and z-scores were computed based on local normative data when available, or published normative data from healthy controls otherwise.