dataesr/scientific-paragraphs-categorization huggingface dataset:
Structure Preparation A crystal-based model of the middle part of the Tpm (Brown et al. [26] , PDB code 2B9C), in which two Cys190 residues form a disulfide bond was used as the starting point for MD simulation of cross-linked Tpm. The models of uncross-linked Tpm and the C190A Tpm mutant were prepared and energy minimized using the CHIMERA package (CHIMERA was developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, CA, USA, supported by NIGMS P41-GM103311  [27] ) and used as the starting point for their simulations.
MD Simulation The MD simulations were performed for 100 ns using GROMACS v. 2016. 3 package with 2 fs time steps  [33]. The protein was immersed in a 9. 5 nm × 9. 5 nm × 24 nm rectangular box filled with water molecules extending at least 15 Å from the protein in each direction and periodic boundary conditions. The ionic strength of 0. 15 M and zero net charge were provided by addition of Na + and Cl -ions. After addition of water molecules, the system was energy minimized. First minimization was performed with the steepest-descent method with harmonic constraints applied to N, C α , and C backbone atoms until a maximum force of 1000 kJ•mol -1 •nm -1 was achieved. Then energy was minimized further without any constraints and a maximum force of 100 kJ•mol -1 •nm -1 was achieved. The system was then heated to 300 or 313 K during a 200 ps long MD run under an NVT (number of particles, volume, and temperature) ensemble with harmonically constrained C α atoms (constraint stiffness of 4 kJ•mol -1 •nm -2 ).
Cloning and expression of H. pylori AP endonuclease in E. coli and purification of the HpXth protein Genomic DNA of H. pylori was provided by the Republican Collection of Microorganisms (Astana, Kazakhstan). Reference gene sequence of xthA of H. pylori was retrieved from the published genome sequences: CP011330. 1 (range: 1144587-1145339). The following PCR primers (shown in the 5'!3' direction) were applied to amplify the target HpXth cDNA: HpXth-NdeI, d(GGGAATTCCATATGAAACTGATTTCATGGAATGTGAAC) and HpXth-BamHI, d(CGCGGATCCGTTAAACTAATTCCAACCCTACCGG). The ORF of XthA from H. pylori was cloned into the pET28c(+) vector at the NdeI/BamHI sites, resulting in expression plasmid pET28c/HpXth. The encoded HpXth protein carries an N-terminal 6xHistag sequence. The DNA sequence of plasmid insert was verified against the sequence from the GenBank database in the Vector NTI software Advance™ v11.
1 mM MgCl 2 , 50 mM HEPES-KOH (pH 6. 8), 0. 01% Nonidet P-40, 0. 05 mM DTT, 0. 1 mgÁmL -1 BSA, and a limited amount of an enzyme, with incubation at 37 ˚C for 1 h, unless specified otherwise. The kinetic parameters of repair reactions were measured as described  [37]. Briefly, 10-6000 nM duplex oligonucleotide substrate was incubated under the appropriate reaction conditions. The reaction products were quantified on a PhosphorImager after separation by denaturing polyacrylamide gel electrophoresis (PAGE). The kinetic constants were measured at the initial velocity, and K M and k cat values were determined by fitting the data to the one-site binding model in Prism 4 (GraphPad Software, USA). The kinetic parameters for AP endonuclease-catalyzed 3'!5' exonuclease reaction were determined by quantifying the reaction products expressed as a percentage of the total substrate.
Phylogenetic analysis and model building The sequences of the conserved domains of E. coli Xth, human APE1 and APE2, Neisseria meningitidis Nape, and Methanothermobacter thermautotrophicus Mth212 were used to search the nonredundant NCBI database of protein sequences by means of BLAST  [39]. One representative sequence from each family per taxonomic class was selected for analysis, unless the same species had two paralogs from the same family, in which case, both were selected. Structural model of HpXth was built by multiple iterative threading with searching of the full PDB database using I-TASSER  [40]. All sequence alignments and phylogenetic trees were built in Clustal Omega  [41]. The conservation analysis was carried out with the Taylor set of amino acid properties  [42]  and the hierarchical analysis approach outlined elsewhere  [43] , except that the conservation at any position was expressed as the mean of the number of crossed borders in the Venn diagrams covering all sequence pairs in the compared alignments and normalized to the number of pairs.
For this experiment, peptides were separated on a Acclaim Pep-Map RSLC column (15 cm × 75 μm, 2 μm particles; Thermo Scientific) with a 75 min multistep acetonitrile gradient (Buffer A: 0. 1% formic acid; buffer B 90% acetonitrile/10% H 2 O in 0. 1% formic acid) at a flow rate of 0. 3 μL/min, according to the following time table: 0 min, 2% B; 10 min, 2% B; 58 min, 50% B; 59 min, 99% B; 69 min, 99% B; 70 min, 2. 0% B; 75 min, 2. 0% B. The unmodified CaptiveSpray ion source (Capillary 1300 V, dry gas 3. 0 L/min, dry temperature 150 ˚C) was employed to interface the LC system with an Impact II (Bruker). For quantification, full-scan MS spectra were acquired at a spectral rate of 2. 0 Hz followed by acquisition of one MS/MS spectrum. For data acquisition from the sample, the two most abundant precursor ions were selected for fragmentation, resulting in a total cycle time of 3 s.
The mass range of the MS scan was set to extend from m/z 150 to 2200 in positive ion polarity mode. We used Mascot software to perform searches against the SwissProt 2014_08 database (546,238 sequences; 194,363,168 residues). Search parameters were set as follows: variable modifications, oxidation (M), fragment ion mass tolerance, 20 ppm; parent ion tolerance, 20 ppm.
cDNA cloning and purification of the HpXth protein The cDNA coding for AP endonuclease HpXth was prepared by PCR from the DNA of H. pylori, and oligonucleotide primers as described in Materials and Methods. The gel-purified PCR 753 bp fragment was inserted into pET28c(+) to create pET28c/HpXth expression plasmid. Competent E. coli DH5α cells were transformed with the ligation mixture, and plasmids containing inserts were isolated from the transformant colonies. The primary structures of inserts in the plasmids were verified by sequencing. A comparison of the cloned cDNA with the respective reference sequences present in GenBank revealed polymorphism in HpXth, manifested in the form of amino acid substitution: G181D. The calculated molecular mass of His-tagged HpXth is 31. 6 kDa. To characterize the DNA repair activities of the recombinant HpXth protein, we affinitypurified the bacterial AP endonuclease from the E.
Homology modeling and phylogenetic analysis of HpXth AP endonucleases belonging to the Endonuclease-Exonuclease-Phosphatase (EEP) superfamily are classified into five families based on their sequence homology: ExoIII-like (with E. coli Xth being the prototypical member), NApe-like (similar to Neisseria NApe endonuclease), Mth212-like (similar to Methanothermobacter Mth212 endonuclease), Ape1-like and Ape2-like (similar to human APE1 and APE2, respectively). Unlike its E. coli homolog, HpXth is classified as an Ape1-like endonuclease by the NCBI Conserved Domain Database  [48]. We re-examined the phylogenetic relations among the EEP superfamily AP endonucleases using a set of 284 sequences evenly spread over all domains of life (Fig 7A and S1 File). HpXth, together with several other bacterial and archaeal sequences, formed a separate clade among the Ape1-like family members (labeled as Archaea+Bacteria in Fig 7A ).
Bacillus subtilis ExoA protein, an efficient AP endonuclease with a low NIR activity  [49] , also fell into this clade. A closer look at Epsilonproteobacteria, the class to which H. pylori belongs, revealed that basal Epsilonproteobacteria possess AP endonucleases from ExoIII-like, Mth212-like, and Ape1-like families, but some of those were lost during the evolution: in Helicobacteraceae, only Ape1-like sequences remain, while its sister group, Campylobacteraceae, retained only Mth212-like AP endonucleases. Multiple threading revealed the best templates for HpXth to be B. subtilis ExoA [PDB entry 5CFE,  [49] ], Archaeoglobus fulgidus AP endonuclease [2VOA,  [50] ], N. meningitidis NApe [2JC5,  [51] ], M. thermautotrophicus Mth212 [3FZI,  [52] ], and 3W2X, unpublished), and human APE1 [2O3H,  [53] ].
Moreover, the non-public code SloopS  [47]  has been extended to the NMSSM  [48, 49]  and applied to the calculation of Higgs decays  [49, 50]. The current work focussing on NMSSM Higgs decays is part of the effort for developing a version of FeynHiggs  [18, [51] [52] [53] [54] [55] [56] [57] ] dedicated to the NMSSM  [25, 58]. The general methodology relies on a Feynman-diagrammatic calculation of radiative corrections, which employs FeynArts  [59, 60] , FormCalc  [61]  and LoopTools  [61]. The implementation of the renormalization scheme within the NMSSM  [25]  has been done in such a way that the result in the MSSM limit of the NMSSM exactly coincides with the MSSM result obtained from FeynHiggs without any further adjustments of parameters (cases where the NMSSM result is more complete than the current implementation of the MSSM result will be discussed below).
Conclusions In this paper, we have presented our evaluation of neutral Higgs decay widths into SM final states in the (CP-conserving or CP-violating) NMSSM. Full one-loop corrections have been included for all the considered channels, as well as higher-order QCD corrections to the decays that are generated at the radiative level. The inclusion of one-loop contributions to the decays into SM fermions or electroweak gauge bosons goes beyond the usual approximation amounting to a QCD/QEDcorrected tree level. In addition, QCD corrections to the digluon and diphoton decay widths have been carefully processed, including the mass dependence in the γγ case and corrections beyond NLO in the gg case. In its current form, this state-of-the-art implementation of the neutral Higgs decays into SM particles is available as a Mathematica package, but should also be integrated into the FeynHiggs code in the near future.
Acknowledgments We thank  T. Hahn ,  M. Mühlleitner ,  P. Slavich ,  M. Spira  and  D. Stöckinger  for fruitful discussions. The work of F. D. and S. H. was supported in part by the  MEINCOP (Spain)  under contract  FPA2016-78022-P , in part by the  "Spanish Agencia Estatal de Investigación" (AEI)  and the  EU "Fondo Europeo de Desarrollo Regional" (FEDER)  through the project  FPA2016-78022-P , and in part by the  AEI  through the grant  IFT Centro de Excelencia Severo Ochoa   SEV-2016-0597. In addition, the work of S. H. is supported in part by the " Spanish Red Consolider MultiDark "  FPA2017-90566-REDC. During different stages of the project, S. P. acknowledges support by the  Collaborative Research Center   SFB676  of the DFG, " Particles, Strings and the early Universe " and by the  ANR  grant " HiggsAutomator " ( ANR-15-CE31-0002 ).
data collection Data were reported on structured and strictly anonymous questionnaires (case report forms) for eligible patients. At inclusion, collected data included demographic and Clinical Care/Education/Nutrition socioeconomic characteristics, relevant medical history, including diabetes complications, CV risk factors, glycemic control (blood glucose monitoring, self-monitoring blood glucose (SMBG), HbA1c, hypoglycemia), vital signs, reason(s) to add-on an insulin therapy to OADs/change in insulin therapy, patient's glycemic goal targeted by the treating physician, life style, antidiabetic therapy at the time and at the end of the visit (ie, all type of antidiabetics including glucagon-like peptide-1 analog). HbA1c laboratory measurement was performed at each visit: at baseline, at 3 months, at 6 months, and at 12 months (end of study) from inclusion.
statistical analysis All data were analysed using SAS (V. 8. 2 or higher). Descriptive analyses and statistical tests (χ 2 test, Fisher test, t-test, Wilcoxon Mann-Whitney test, Wilcoxon test) were used as appropriate. Statistical analyses were performed at the 5% global significance level using two-sided tests. Univariate and multivariate logistic regression analyses were performed to identify clinical and non-clinical predictive factors for achieving glycemic control (HbA1c level targeted by the physician) at 6 and 12 months. Univariate OR was presented with its 95% CI. All significant variables in univariate statistical test at the 0. 20 level were included in the multivariate initial model. A stepwise procedure was used with an entrance significance level at 20% and a removed significance level at 5%.
However, with only two sources, a larger spectroscopic sample is clearly required in order to improve our understanding of the properties of z ≥ 4 SMGs. To increase the sample size of high-redshift SMGs, we have undertaken the ALMA-SCUBA-2 survey of the UDS field (AS2UDS): an ALMA Band 7 survey of all 716 submillimeter sources detected in the UKIDSS Ultra Deep Survey field by SCUBA-2 on the James Clerk Maxwell Telescope (JCMT;  Geach et al. 2017). This survey has precisely located 695 SMGs  (Stach et al. , in preparation). Here we examine the ALMA datacubes to search for serendipitous emission lines. The frequency coverage of our data is 336-340 and 348-352 GHz, corresponding to z = 4. 40-4. 46 and z = 4. 60-4. 66 for [C II]. We aim to spectroscopically confirm [C II] emission line sources at z ≃ 4.
ALMA data The UDS 0. 96 degree 2 field was observed at 850 µm with SCUBA-2 as part of the Cosmology Legacy Survey  (Geach et al. 2017 ) to a depth of σ 850 ≃ 0. 9 mJy beam -1 , detecting 716 submillimeter sources above 4σ, S 850 ≃ 3. 6 mJy. We observed all 716 of these submillimeter sources with ALMA at 870 µm in Band 7 to pinpoint the galaxies responsible for the submillimeter emission. The data were taken in the period 2013 November to 2017 May (Cycles 1, 3, and 4) with a dual polarization set up. The full data reduction and catalogue will be presented in  Stach et al. (in preparation). In brief, our observations cover a total bandwidth of 7. 5 GHz split into two sidebands: 336-340 GHz and 348-352 GHz. The synthesised beam of our observations is 0. 15-0. 3 arcsec full-width, -Emission lines detected in the AS2UDS Band 7 datacubes, ranked by their integrated signal-to-noise.
half maximum (FWHM), adopting natural weighting. The primary beam of ALMA is ∼ 18 arcsec FWHM, which covers the SCUBA-2 beam (FWHM∼ 14. 5 arcsec). This coverage, combined with the higher resolution and greater depth of the ALMA observations, means that we expect to detect the sources responsible for the original SCUBA-2 detections in the ALMA continuum data. Each pointing was centred on the SCUBA-2 catalogue position and observed for a total of ∼ 40 s. A subset of 120 of the pointings were observed in both Cycle 3 and 4 and thus have a longer total integration time (typically 80-90 s). All data were processed using the Common Astronomy Software Application (casa;  McMullin et al. 2007 ). We construct cleaned, tapered continuum maps and dirty, tapered data cubes. For more reliable line detections, we image the cubes without applying any cleaning to deconvolve the beam.
Given the non-Gaussian nature of the noise in the ALMA data cubes, to determine the purity of the sample and hence an acceptable S/N threshold for our detections, we calculate an empirical false positive rate by applying the same procedure to the inverted, velocitybinned, continuum-subtracted cubes at the AS2UDS source positions. This false positive rate is dependent on the velocity binning of the spectra. We require a threshold for selection that produces a false detection rate of ten percent. For a false positive rate of ten percent in our final sample, we take an integrated S/N cut which varies depending upon the velocity binning with S/N = 8. 0 for 50 km s -1 channels, S/N = 7. 5 for 100 km s -1 channels and S/N = 7. 0 for 200 km s -1 channels. We detect significant emission lines in ten SMGs above these limits.
We plot all ten line emitters in Figure  1  and list their properties in Tables  1  and 2. To ensure we identify all bright line emitters within the ALMA pointings, we run two additional line searches. First, two of the SMGs where we have identified an emission line lie in ALMA maps which contain a second SMG. In these cases we extract the spectra of this second SMG and search for (lower-significance) emission lines at similar frequencies to the detected emission line. In one of these SMGs (AS2UDS. 0109. 1) we found a tentative S/N = 5. 3 emission line corresponding to the same redshift as the detected emission line source the linear fit produced a good fit to the data without over-fitting. Fig. 2. -Thumbnails of the line emitters detected in our survey. Top row in each panel: 3 ′′ × 3 ′′ thumbnails with ALMA continuum contours overlaid at 3, 4, 5, 10, and 20σ on background images.
63 ± 0. 01. h AS2UDS. 0535. 0 has optical and near-infrared properties which may indicate the line we detect is CO(5-4), corresponding to z CO = 0. 70 ± 0. 01. i Uncertainties on median values are the standard error. j Supplementary sources are those within the same ALMA map as a detected line emitter (but not detected above our S/N threshold), which appear to have a low-significance emission line at a similar frequency to their detected companion. the current data we are unable to estimate more precise magnification factors. We next estimate the line luminosities of the two sources where the submillimeter emission is spatially coincident (within 0. 5 ′′ ) with a B-band detection: AS2UDS. 0243. 0 and AS2UDS. 0535. 0, assuming these correspond to high-J 12 CO lines. We compare these luminosities to other studies of high-J 12 CO emission lines to see whether it is plausible that these lines are high- J 12 CO rather than [C II].
The photometric redshifts of AS2UDS. 0243. 0 and AS2UDS. 0535. 0 are reported in Table  2. At these redshifts the emission lines would correspond to CO (8 -7) at z = 1. 63 ± 0. 01 with L CO(8-7) = 1. 5 × 10 8 L ⊙ for AS2UDS. 0243. 0 and CO (5 -4) at z = 0. 70 ± 0. 01 with L CO(5-4) = 0. 2 × 10 8 L ⊙ for AS2UDS. 0535. 0. These luminosities are approximately an order of magnitude brighter than found in typical local ULIRGs (e. g. Arp 220;  Rangwala et al. 2011)   Fig. 3. -[C ii] FWHM versus line luminosity for the AS2UDS [C ii] emitters. We compare our sample to star-forming galaxies and AGN from the literature. The dashed line shows the 1σ limit for false positives in the AS2UDS sample (i. e. 84 percent of false positives lie to the left of this line). The solid line shows a FWHM ∝ L 0. 5 [CII] relation scaled to the median of the AS2UDS data points.
Continuum data [CII] data Continuum Gaussian [CII] Gaussian Beam Fig. 6. -Average radial profiles of the dust continuum and [C ii] emission in our SMGs from the stacked images. The solid black and dashed red lines show the profile derived using a 2D Gaussian fit to the stacked data for continuum and [C ii] emission respectively. The profiles have been normalized to compare them: the [C ii] emission is more extended than the continuum emission. Uncertainties on the Gaussian profiles were determined using a bootstrap analysis. Error bars on the abscissae show the size of the radial bins. The points have been offset by ±0. 01 ′′ for clarity. 2σ limits are shown for non-detections. The dotted line shows the ALMA beam profile for reference.
CONCLUSIONS We have used ALMA at 870 µm to observe a sample of 716 SCUBA-2-selected sources brighter than S 850 ≥ 3. 6 mJy (4σ) in the UKIDSS UDS field. With high resolution (0. 15 ′′ -0. 30 ′′ ) ALMA observations we detect the submillimeter galaxy counterparts to the single-dish submillimeter sources. We use these data to identify bright line emitters that fall in the 7. 5 GHz bandwidth of our ALMA observations. We detect ten line emitters above a signal-to-noise of 7, corresponding to a false detection rate of ten percent (as derived from inverting the data cubes). All of these line emitters are 870 µm continuum-detected sources in our parent survey with S 870 1 mJy. The majority of these line emitters have multi-wavelength properties consistent with [C II] λ157. 8 µm emitters at z = 4. 4-4.
Gene ontology (GO) analysis  28  (http://geneontology. org/) was performed on the 150 test transcripts that most highly correlated with NES (all corr. >0. 67, p-value < 0. 0001) (Table  S2 ). The most significant over-represented groups were related to vascular or EC function (Fig. 1A ). We used REViGO  29  to summarise and remove redundant terms from all GO groupings identified (Table  S2 ); 'circulatory system development' was the stand-alone most significant (p-value 10 18 ) (Fig. 1B ). Consistent with these functional groupings, of the 150 test transcripts that most highly correlated with NES, we had previously identified >50% as being highly EC-enriched across human organs  30  , e. g. CLEC14A, ROBO4, TIE1, SOX17, TEK, ESAM, NRP1 and CD34 (corr. 0. 77, 0. 73, 0. 73, 0. 73, 0. 72, 0. 71, 0.
0001) (Fig. S1A-F ), in this replication dataset. This analysis indicated that NES transcript expression is enriched in EC across organs, and we used protein profiling to confirm that nestin protein was specifically expressed in the EC compartment of the human adult cerebral cortex, adrenal gland, thyroid, skeletal muscle, lung, tonsil, spleen, pancreas, salivary gland, esophagus, stomach, duodenum, colon, urinary bladder, adipose, placenta, ovary, testis and prostate (Fig. 1D ). Nestin was also expressed in EC of the heart, kidney, and breast, although in these tissues, consistent with previous reports  [32] [33] [34]  , non-EC expression was observed in cardiomyocytes, renal glomeruli, and myoepithelial cells, respectively (Fig. 1E ).
EC proliferation is not a pre-requisite for nestin expression in vivo. The vast majority of the adult human vasculature is quiescent  35  , but as nestin expression is currently considered largely restricted to progenitor or proliferating cells, we investigated the proliferative status of nestin-positive EC. In the HPA dataset, NES transcript TPM values did not positively correlate with those for the proliferation markers PCNA (proliferating cell nuclear antigen), MKI67 (antigen KI-67) or CDK2 (cyclin-dependent kinase 2), which are expressed in replicating EC  [36] [37] [38]  (corr. -0. 25, -0. 31 and 0. 12, respectively) (Fig. 2A-C ). PCNA, KI67 and CDK2 protein was expressed in the highly proliferative hematopoietic cells of the bone marrow (Fig. 2D , row 1), occasional EC in the placenta (Fig.
RNAseq data for NES and the EC transcripts, PECAM1 (CD31) and CD34, in kidney renal clear cell carcinoma (KIRC), bladder urothelial carcinoma (BLCA), lung adenocarcinoma (LUAD), stomach adenocarcinoma (STAD), glioblastoma multiforme (GBM) and corresponding normal tissue, was downloaded from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project. Protein profiling and survival analysis was performed as part of our HPA pathology atlas  44. CD34 and PECAM1 levels were elevated in KIRC vs. normal kidney (mean Log2 KIRC vs. normal kidney: CD34 12. 1 vs. 11. 5, PECAM 12. 1 vs. 10. 7, both p-value < 0. 0001) (Fig. 3A ), consistent with reports that KIRC is highly-vascularised  45. In contrast, NES was decreased (mean Log2 KIRC vs. normal kidney: NES 11. 1 vs. 11. 7 vs. , p-value < 0.
8 vs. 11. 5, PECAM 10. 2 vs. 12. 5, CD34 9. 6 vs. 11. 4, all Figure  1. Nestin is a pan-EC enriched protein in the human adult. RNA-seq data from 176 individual samples from 37 different human tissues were used to generate Spearman pair wise correlation values between NES transcript expression and transcripts for all other mapped protein coding genes. Gene ontology (GO) analysis was performed on the 150 transcripts that were most highly correlated with NES: (A) the 10 most significant GO functional groupings and (B) a summary of GO functional groupings with removal of redundant terms (plot produced using REVIGO [http://revigo. irb. hr/] before modification). (C) Correlation plots showing the relationship between NES and the EC-enriched transcripts CLEC14A, ROBO4, TIE1, SOX17, TEK, ESAM, NRP1 and CD34.