dataesr/scientific-paragraphs-categorization huggingface dataset:
Recently, we reported that the chance of achieving DMARD-free sustained remission in clinical practice has become a more feasible outcome with up-to-date treatment strategies  [5]. The Leiden EAC patients who were evaluated in the present study were included during the period 1993-2006. Treatment strategies have changed over time in these patients and indeed patients included in later periods had a higher chance of achieving DMARD-free sustained remission (data not shown). All analyses in the present study were adjusted for the inclusion period as a proxy for the initially applied treatment strategy, and the results obtained for IL2RA were thus independent of the effect of changes in treatment strategies. Another potential limitation is that we evaluated data from longitudinal observational cohort studies.
These data reflect the daily care of patients and not only decisions to start DMARDs but also decisions to stop DMARDs were left to the patients' and rheumatologists' decisions and not protocolized. In the ESPOIR cohort, mainly in the first years of its existence, quitting DMARD therapy was uncommon. Consequently, the observed frequency of DMARD-free sustained remission may be underestimated. This may be one of the explanations contributing to a lower incidence of DMARD-free sustained remission in the ESPOIR cohort. In addition, whether DMARD-free sustained remission was achieved was determined slightly differently in the cohorts. In the Leiden EAC cohort, all medical files were checked to ensure that DMARD-free sustained remission was present. In the ESPOIR cohort, data from the structured visits with yearly intervals were studied.
It is possible that more patients included in the ESPOIR cohort would have achieved DMARD-free sustained remission when all information present in medical files was evaluated. Thirdly, the follow-up duration was shorter in the ESPOIR cohort. Differences in common practice for discontinuing DMARD therapy, however, might be the most important cause for the higher frequency of DMARD-free sustained remission in the Leiden EAC cohort than in the ESPOIR cohort. Nonetheless, there was a strong tendency in the data from the ESPOIR cohort validating the importance of IL2RA for the disease course in RA. The SE alleles were strongly associated with sustained DMARD-free remission. A similar result was previously reported (although using a dominant model instead of an additive model). We here observed that this association was not independent of ACPA, suggesting that the SE alleles act in the same path as ACPA.
These measurements show that electroweak bosons are essentially unmodified by the hot and dense medium. In this paper, Z boson production at √ s NN = 2. 76 TeV is studied using PbPb collision data collected in 2011, which corresponds to an integrated luminosity of about 166 µb -1. From this PbPb data-taking period, the ATLAS collaboration published Z boson yields showing no deviation with respect to theoretical predictions  [17]. The set of pp data at the same centre-of-mass energy recorded in 2013 by CMS, with a total integrated luminosity of 5. 4 pb -1 , is used to measure pp yields. The nuclear modification factor (R AA ), the ratio of PbPb and pp yields scaled by the number of inelastic nucleon-nucleon binary collisions, is then calculated. These larger PbPb and pp data samples allow a more precise measurement of the Z boson yield dependence on transverse momentum (p T ), rapidity (y), and collision centrality.
The trigger efficiencies for the Z → e + e -channel are approximately 96% and 99% for Z bosons produced in PbPb and pp collisions, respectively. The difference comes from the energy-clustering algorithms used at the trigger level in PbPb  [23]  and pp  [24]  collisions. Centrality for PbPb collisions is defined by the geometrical overlap of the incoming nuclei, and allows for splitting up the PbPb data into centrality classes ranging from peripheral, where there is little overlap of the colliding nuclei, to central, where there is nearly complete overlap of the colliding nuclei. In CMS, the centrality of a PbPb collision is defined through bins that correspond to fractions of the total hadronic inelastic cross section as observed in the distribution of the sum of the transverse energy deposited in the HF calorimeters  [21].
The dimuon system rapidity is limited to |y| < 2. 0, while the rapidity of the dielectron system is limited to |y| < 1. 44. Figure  1  shows the dimuon and the dielectron invariant mass spectra in the 60-120 GeV/c 2 mass range after applying acceptance and selection criteria in PbPb and pp collisions. The filled histograms are from the MC simulation described in Section 5. 2. In the PbPb sample (top row), 1022 dimuon events (left column) with opposite-charge pairs (OC, black solid circles) and no events with same-charge pairs (SC, black open squares) are found in the Z boson mass range. The pp sample (bottom row) has 830 OC muon pairs and 1 SC pair. In the more restricted dielectron y range (right column), 328 (388) OC pairs are found in the PbPb (pp) data sample, with  T > 20 GeV/c in PbPb (top right) and in pp (bottom right) collisions.
Full black circles represent opposite-charge lepton pair events and open black squares represent same-charge lepton pair events. Superimposed and normalized to the number of Z boson candidates in data is the MC simulation from PYTHIA NN → Z → µ + µ -or e + e -, where N is a nucleon from the proper mix of protons and neutrons, embedded in HYDJET simulated events for the PbPb case, and pp → Z → µ + µ -or e + e -for the pp case. 27  (17)  SC pairs. The increased rate of SC pairs in the dielectron channel results from higher rates of electron misreconstruction and charge misidentification. The charge misidentification rate is estimated for electrons and results in a 1% correction for Z bosons in PbPb collisions. The SC lepton pairs provide a measurement of the combinatorial background, which is negligible (at the 0.
Finally, the generated Z boson p T distribution is reweighted according to the p T distribution obtained using the pp → Z → µ + µ -POWHEG  [32] [33] [34] [35]  next-to-leading-order (NLO) event generator at 2. 76 TeV with the CT10 PDF set  [36]  that gives a reasonable description of the 7 TeV measurement  [8]. The distribution of the longitudinal position of the primary vertex is reweighted to match the one observed in collision data. For the pp data sample, Z boson events are generated with the PYTHIA 6. 424 generator with tune Z2* that matches the charged particle multiplicity measured by CMS at √ s values of 0. 9, 2. 36, and 7 TeV  [37]. The generated Z boson p T distribution is reweighted according to the same POWHEG p T distribution used in PbPb. These generated events are reconstructed with the same software and algorithms used for the pp collision data.
Z boson yields in PbPb collisions vs. p T , y, and centrality The yield of Z bosons has been measured in PbPb collisions as a function of event centrality, Z boson y and p T , and then compared to that in pp collisions simulated using POWHEG, scaled by an average nuclear overlap function (T AA ), as described below and discussed in Ref. [25]. Simulated pp collisions from POWHEG are used in these first comparisons because of their higher statistical precision. As shown in Section 6. 1, the pp data are consistent with the simulations. A direct comparison of PbPb and pp data is shown in Section 6. 3. The data are divided into independent ranges: 6 in event centrality, 8 (5) in y for the dimuon (dielectron) channel, and 7 in the dilepton p T. The results are presented in Figs. 3  and 4. The yields of Z → + -(where is µ or e) per MB event, per unit of y (dN Z PbPb /dy), and per p T bin (d 2 N Z PbPb /dy dp T ) are computed using the following equations: dN Z PbPb dy = N PbPb (Z → + -) αεN MB ∆y or d 2 N Z PbPb dy dp T = N PbPb (Z → + -) αεN MB ∆y∆p T.
Nuclear modification factor Based on PbPb and pp data at the same centre-of-mass energy, the nuclear modification factor, R AA , is computed for both the dimuon and dielectron channels as a function of the Z boson p T , y, and event centrality, as follows: R AA = N Z PbPb T AA × σ Z pp ≡ N Z PbPb N coll × N Z pp ( 4 ) where N Z PbPb (N Z pp ) are the yields per MB event measured in PbPb (pp) collisions corrected for acceptance and efficiency, σ Z pp refers to the differential cross sections measured from pp collisions, N coll refers to the average number of inelastic nucleon-nucleon collisions for the  The yields are compared with pp → Z → + -POWHEG predictions scaled by the 0-100% centrality averaged T AA. The light gray bands in the results vs. p T represent the theoretical uncertainty of 5% assumed for the POWHEG reference curve together with the uncertainty of 6.
Combined results for the two decay channels According to lepton universality and given the large mass, the Z boson is expected to decay into the dimuon and dielectron channels with branching ratios within 1% of each other. Also, neither muons nor electrons are expected to interact strongly with the medium formed in the collision. The two channels can therefore be checked against each other, and used to measure the combined Z → + -yields and R AA , where Z → + -refers to the Z boson decaying into either the dimuon or dielectron channel. Given the uncertainties in the measurements, in the region of overlap, the datasets are in agreement. The combination is then done following the best linear unbiased estimate technique, as described in Ref. [41]. The combined yields per MB event for PbPb collisions and the combined cross sections for pp collisions are shown in Figs.
To calculate the combined R AA , the combined dilepton yields in PbPb and pp data are obtained and then the R AA ratio is calculated based on those values. The combined R AA values are given in Table  3  and in Fig. 8. The R AA for the combination of the two channels shows no dependence and no variation in nuclear effects as a function of p T , y, or centrality. This demonstrates that within uncertainties, Z boson production is not modified in PbPb collisions compared with pp collisions scaled by the number of inelastic nucleon-nucleon collisions.
Summary The yields of Z bosons have been measured as a function of p T , y, and centrality, in both the dimuon and dielectron channels for PbPb collisions at √ s NN of 2. 76 TeV with an integrated luminosity of approximately 166 µb -1. The Z → µ + µ -and Z → e + e -cross sections have been measured in pp collisions at the same collision energy with an integrated luminosity of 5. 4 pb -1. Within the combined statistical and systematic uncertainties, no centrality dependence is observed once the yields are normalized by the number of inelastic nucleon-nucleon collisions. When integrated over centrality, the Z boson y and p T distributions are found to be consistent between the PbPb and pp data and also to agree with theoretical predictions. The centrality-integrated R AA is found to be 1. 06 ± 0.
Cardiac rehabilitation program At the beginning and at the end of the CR program, each patient underwent a cardiopulmonary exercise test performed on a cycle ergometer. This symptom limited cardiopulmonary exercise test started with an initial workload of 20 watts with increments of 10 watts at each 1-min exercise stage. During that test, peak VO2 (ml/kg/min) and ventilatory threshold (ml/kg/min) were measured. Ventilatory and gas exchange data were determined on a breath-by-breath basis with a computerized system. Peak oxygen consumption (peak VO2) was defined as the highest consecutive 30-s averaged value obtained during exercise test  [29]. Ventilatory Threshold was estimated by the Wasserman method as the point where ventilatory equivalent ratio for oxygen (VE/VO2) starts to increase without concomitant increase in the ventilatory equivalent ratio for carbon dioxide (VE/VCO2)  [30].
Statistical analysis Data are expressed as means ± Standard Deviation. Statistical calculations were performed using the SPSS software package (SPSS Inc. , Chicago IL, USA). Comparisons of means between groups were performed by two-tailed Student's t-test. Comparisons of percentages between groups were performed by Chi-2 test. When comparing percentages with an expected count smaller than 5 in the 2 × 2 contingency table, the Chi-2 with the Yates correction was used. Baseline and post-cardiac rehabilitation data were compared by paired t-test. The correlation coefficients (r) were determined by linear regression analysis. Statistical significance of the correlation coefficients was determined by the method of Fisher and Yates. Multivariable analysis was performed by stepwise linear regression for continuous dependent variables or by stepwise logistic regression for dichotomous dependent variables.
Baseline characteristics Among the 64 patients included in the study, 57 completed the study. The drop out of 7 patients was due to personal reasons and occurred during the initial period of the CR program. The baseline data of the patients who completed the study, in each treatment group (intensive treatment group, control treatment group) are shown in Table  1. No significant differences were seen between the 2 groups for gender, age, diabetes duration, history of previous Coronary Heart Disease (CHD), tobacco smoking, BMI, type of ACS, resting heart rate, systolic and diastolic blood pressure, use of antidiabetic agents at time of inclusion in the study (metformin, sulfonylurea or glinide, acarbose, pioglitazone, DPP-4 inhibitor, insulin), use of cardiovascular drugs (ACE inhibitor/ARB, betablocker, antiplatelet agent, statin), baseline values of HbA1c, fructosamine, ventilatory threshold and VO2 peak.
Methods DNA constructs. Cloning of TAF2, TAF8 and TAF10 expression constructs in MultiBac plasmids pPBac  38  , pFL and pIDC  53  is detailed in the Supplementary Methods. Expression plasmids for subcomplexes TAF5-6-9 (pPBac-3TAF) and TAF4-12 (pDiFB-412) and Importin a1 DIBB were described previously  12, 54. Truncated Importin a1 (residues 71-497) was generated by amplifying the coding region of Importin a1 DIBB by PCR. All constructs were verified by DNA sequencing. Sequence alignments. Alignments were generated using the ClustalW2 server  55  and plotted with ESPript (http://espript. ibcp. fr)  56. Protein sequences for human TAF3 (UniProt accession number Q5VWG9) and human SPT7L (O94864) were retrieved from the UniProt server (www. uniprot. org). Protein production and purification. MBP-TAF8-fusion proteins were produced in E.
5 and crystallization solution containing 1. 4 M Na/K PO 4 at pH 7. 6. Crystals grew in space group P3 1 21 with cell dimensions of a ¼ b ¼ 51. 3 Å and c ¼ 144. 8 Å. Crystals were cryoprotected by adding 20% (v/v) glycerol and flash frozen in liquid nitrogen. Diffraction data were collected at 100 K on beamline PROXIMA 1 using a Pilatus 6 M detector (SOLEIL synchrotron, Gif-sur-Yvette, France) and were integrated and scaled using X-ray Detector Software (XDS)  57. The structure of TAF8-10 was solved by the Sulfur-SAD method. A partial model could be built into the experimental electron density map by iterative rounds of density modification and automated structure building using programs Pirate and Buccaneer from the CCP4i suite  58. The model was used to phase a high-resolution data set by molecular replacement using Phaser  58, 59.
3 Å, b ¼ 77. 7 Å and c ¼ 128. 6 Å. Crystals were cryoprotected by the addition of 30% (v/v) ethylene glycole and flash frozen in liquid nitrogen. Data sets were collected at 100 K on beamline ID14-1 using an ADSC Quantum Q210 detector (European Synchrotron Radiation Facility ESRF, Grenoble, France). Diffraction data were integrated and scaled using XDS  57. The structure of Importin a1/TAF8-NLS was solved by molecular replacement using Importin a1 (PDB ID 3RZ9) as a search model. The Importin a1/TAF8-NLS structure was built and refined with Coot  61  and Phenix  62  , respectively, including TLS parameter, occupancy and individual B-factor refinements. Surface plasmon resonance. Biosensor experiments were performed at 25 °C on a BIACORE 3000 (Biacore AB, Uppsala). TAF2 ligand was immobilized onto CM5 sensor chips (GE Healthcare) to a level of 2,500 RU using amine-coupling chemistry.
Truncation mutants of TAF8 fused C-terminally to MBP were serially diluted into running buffer (25 mM HEPES-NaOH, pH 7. 0, 300 mM NaCl, 0. 01% (v/v) NP-40). For association phase, 150 ml of analyte at a concentration of 500 nM were injected at a flow rate of 25 ml min À 1 and dissociation phases were monitored for 200 s by injecting running buffer only. Binding responses were recorded and responses from referencing sensorgrams were subtracted using BIAevaluation software (GE Healthcare). Data were globally analysed with the analysis software. Isothermal titration calorimetry. Calorimetric experiments were conducted in duplicates with a MicroCal iTC 200 instrument (GE Healthcare) at 25 °C. Importin a1 (residues 71-479) and the TAF8 NLS peptide (residues 288-NPYLRPVKKP-KIRRKKSLS-310) were extensively dialysed against ITC buffer (25 mM Tris-HCl pH 8.
0, 150 mM NaCl, 1 mM b-mercaptoethanol) and used at concentrations of 39 mM and 1. 5 mM, respectively. Protein concentrations were determined by absorbance spectroscopy at 280 nm with calculated extinction coefficients of 48,930 M À 1 cm À 1 for Importin a1 and 1,490 M À 1 cm À 1 for the peptide. TAF8 peptide (1. 5 ml) was injected for 3 s with a spacing of 180 s between injections into 200 ml of Importin a1. Heat changes were recorded over 26 injections. Calorimetric titration data were integrated, corrected for heat of dilution of the TAF8 peptide alone and analysed using Origin software version 7. 0 according to a one-site binding model. Binding stoichiometry (n), association constant (K a ), binding enthalpy (DH) and entropy change (DS) were deduced from fitted isotherms by nonlinear regression.
Images were analysed using the Dot Blot Analyzer tool in ImageJ. Analytical ultracentrifugation. Sedimentation velocity experiments were performed in a Beckman XL-I analytical ultracentrifuge (Beckman Coulter). The purified proteins and protein complexes TAF2, TAF8-10 and TAF2-8-10 were loaded into sapphire-windowed cells with 12-mm optical path length and spun in an An-60Ti rotor (Beckman Coulter). Absorbance at 280 nm was measured for 16 h at 42,000 r. p. m. and 10 °C. The data were analysed in terms of continuous sizedistribution (c(s)) with the Sedfit program  63  , considering 200 particles with sedimentation coefficients, s, between 0. 1 and 20 S. A partial specific volume of 0. 73 and frictional ratios of 1. 4 (TAF2, TAF2-8-10) and 1. 6 (TAF8-10) were used. A regularization procedure with confidence level of 0.
68 was applied. Sample densities and viscosities were determined with Sednterp 64 to 1. 023 g ml À 1 and 1. 40 mPa. s (TAF2, TAF2-8-10) and 1. 021 g ml À 1 and 1. 31 mPa s (TAF8-10). Native MS. Purified TAF2-8-10 complex (30 ml) was buffer exchanged into 500 mM ammonium acetate buffer (pH 7. 5) using Amicon spin concentrators (Millipore, 10 kDa MWCO). All MS experiments were performed on a Quadrupole Time-of-flight (Q-ToF) II mass spectrometer (Waters, Manchester, UK) in the positive ion mode  65. For data acquisition, 2 ml of the sample was injected into the mass spectrometer with gold-coated capillary needles made in-house using a needle puller (Harvard Apparatus, Holliston, MA, USA). MS spectra were acquired using a capillary voltage of 1. 7 kV and cone and collision voltages of 100 V. Time-offlight and analyser pressures were at 5.
6 Â 10 À 6 and 4. 2 Â 10 À 4 mbar, respectively. Data sets were acquired and processed with MassLynx V4. 1 software (Waters, UK) with minimal smoothing and no background subtraction. The recorded mass spectra were calibrated externally using 100 mg ml À 1 caesium iodide in water. CLMS analyses. 7TAF complexes were produced as described  12. 8TAF complexes were reconstituted from purified 7TAF complexes by adding twofold molar excess of TAF2 and removal of unbound TAF2 by SEC. 7TAF (200 mg) and 8TAF complexes (200 mg) were crosslinked by BS3 (Bis-sulfosuccinimidyl suberate, Thermo Scientific) at complex/BS3 ratio of 1:5 (w/w) in crosslinking buffer (25 mM HEPES-NaOH, pH 7. 6, 150 mM NaCl, 1 mM DTT) for 2 h on ice. The reaction was quenched by adding saturated ammonium bicarbonate solution followed by incubation on ice (45 min).
Dynamic exclusion was set to 90s and repeat count was 1. Data processing. The mass spectrometric raw files were processed into peak lists using MaxQuant (version 1. 3. 0. 5) (ref. 41) at default parameters except for 'top MS/MS peaks per 100 Da' being set to 100. Search was conducted against TAF complex sequences using Xi software (version 1. 3. 355). Search parameters were MS accuracy, 6 p. p. m. ; MS/MS accuracy, 20 p. p. m. ; enzyme, trypsin; crosslinker, BS3 (including BS3 modification); max. missed cleavages, 4; fixed modification, carbamidomethylation on cysteine; variable modifications, oxidation on methionine; crosslinkable amino acids, N terminus, lysine, serine, tyrosine and threonine; fragments, b and y ions with loss of H 2 O, NH 3 and CH 3 SOH. The data have been validated by 5% FDR with manual validation.
UniProt protein accession numbers of the protein sequences used to search the database were as follows: TAF2 (Q6P1X5-1; with a sequence variation R 785 G; European Nucleotide Archive AAC68502. 1), TAF4 (O00268-1), TAF5 (Q15542-1), TAF6 (P49848-1), TAF8 (Q7Z7C8-1), TAF9 (Q16594-1), TAF10 (Q12962-1), and TAF12 (Q16514-1). Crosslinks observed in artificially introduced sequences (for example, TEV cleavage sites in polyproteins or purification tags) were not included in the search. The MS data were deposited to the ProteomeXchange Consortium 66 via the PRIDE partner repository with the data set identifier PXD001454 (http://www. proteomexchange. org). Antibody production and purification. TAF2 antibodies were generated by immunizing rabbits with purified TAF2. Antibody purification was done as described  67  with the following modifications: 2 mg of recombinant full-length human TAF2 were fixed on 400 ml Affi-Gel 10/15 beads (Bio-Rad) for 2 h at 4 °C with gentle agitation in PBS.
A fully automated 12-steps MudPIT run was performed during which each full MS scan (from 300 to 1,700 m/z range) was followed by 20 MS/MS events using data-dependent acquisition  69. Proteins were identified by database searching using SEQUEST with ThermoProteome Discoverer 1. 4 (Thermo Fischer Scientific)  71. Tandem mass spectra were searched against a human protein sequence database (from the Homo sapiens 2013-04-03 Swissprot release). In all searches, cysteine residues were considered to be fully carboxyamidomethylated ( þ 57 Da statically added) and methionine to be oxidized ( þ 16 Da dynamically added). Relative protein abundance for each protein in a given sample was estimated by normalized spectral abundance factor  72. Normalized spectral abundance factor values were calculated from the spectral counts of each identified protein.
Larger proteins tend to contribute more peptide/ spectra and, therefore, spectral counts were divided by protein length to provide a spectral abundance factor (SAF). SAF values were then normalized against the sum of all SAF values in the corresponding run allowing the comparison of protein levels across different runs. The MS proteomics data were deposited to the ProteomeXchange Consortium 66 via the PRIDE partner repository with the data set identifier PXD001427. Immunofluorescence. Indirect immunofluorescence tests were performed as described  30  with the following modifications: cells were fixed with 4% paraformaldehyde for 15 min at room temperature (RT) and then permeabilized with 0. 1% Triton-X100 for 20 min at RT, incubated for 1 h at RT with either an anti-TAF2 (rabbit polyclonal serum; 3038; described above; diluted 1:100) þ anti-TAF8 (mouse monoclonal antibody (mAb) 1FR-1B6 (ref.