144 research outputs found

    Comprehensive glycosylation profiling of IgG and IgG-fusion proteins by top-down MS with multiple fragmentation techniques

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    We employed top- and middle-down analyses with multiple fragmentation techniques including electron transfer dissociation (ETD), electron capture dissociation (ECD), and matrix-assisted laser desorption ionization in-source decay (MALDI-ISD) for characterization of a reference monoclonal antibody (mAb) IgG1 and a fusion IgG protein. Fourier transform ion cyclotron resonance (FT-ICR) or high performance liquid chromatography electrospray ionization (HPLC-ESI) on an Orbitrap was employed. These experiments provided a comprehensive view on the protein species; especially for different glycosylation level in these two proteins, which showed good agreement with oligosaccharide profiling. Top- and middle-down MS provided additional information regarding glycosylation sites and different combinational protein species that were not available from oligosaccharide mapping or conventional bottom-up analysis. Finally, incorporating a limited enzymatic digestion by immunoglobulin G-degrading enzyme of Streptococcus pyogene (IdeS) with MALDI-ISD analysis enabled extended sequence coverage of the internal region of protein without pre-fractionation. Biological significance: Oligosaccharide profiling together with top- and middle-down methods enabled: 1) detection of heterogeneous glycosylated protein species and sites in intact IgG1 and fusion proteins with high mass accuracy, 2) estimation of relative abundance levels of protein species in the sample, 3) confirmation of the protein termini structural information, and 4) improved sequence coverage by MALDI-ISD analysis for the internal regions of the proteins without sample pre-fractionation

    Growth accounting in economic history:Findings, lessons and new directions

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    There is now a large volume of growth accounting estimates covering the long run experience of advanced countries. However, most of the studies in economic history are not based on state-of-the-art methods. There is a trade-off between maintaining international comparability and achieving the best results for individual countries. A one-size-fits-all approach will not always do justice to the variety of historical experiences since the conventional assumptions may sometimes be inappropriate. Nevertheless, growth-accounting studies have produced some eye-catching results which provide food for thought both for economic historians and for growth economists. These include (1) the finding that TFP growth was comparatively slow during the First Industrial Revolution, (2) Solow's famous conclusion that TFP growth accounted for 7/8ths of American labour-productivity growth was atypical, (3) the impact of new general-purpose technologies on growth typically takes a long time to materialize, ICT being the notable exception and (4) that capital-deepening was much more important relative to TFP growth in east Asian than in western European catch-up growth. Growth accounting is undoubtedly a valuable item in the cliometrician's toolkit. Nonetheless, we anticipate the introduction of more sophisticated methods and look forward to progress in understanding what explains marked differences in TFP performance

    Guidelines for chemotherapy of biliary tract and ampullary carcinomas

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    Few randomized controlled trials (RCTs) with large numbers of patients have been conducted to date in patients with biliary tract cancer, and standard chemotherapy has not been established yet. In this article we review previous studies and clinical trials regarding chemotherapy for unresectable biliary tract cancer, and we present guidelines for the appropriate use of chemotherapy in patients with biliary tract cancer. According to an RCT comparing chemotherapy and best supportive care for these patients, survival was significantly longer and quality of life was significantly better in the chemotherapy group than in the control group. Thus, chemotherapy for patients with biliary tract cancer seems to be a significant treatment of choice. However, chemotherapy for patients with biliary tract cancer should be indicated for those with unresectable, locally advanced disease or distant metastasis, or for those with recurrence after resection. That is why making the diagnosis of unresectable disease should be done with greatest care. As a rule, pathological diagnosis, including cytology or histopathological diagnosis, is preferable. Chemotherapy is recommended in patients with a good general condition, because in patients with general deterioration, such as those with a performance status of 2 or 3 or those with insufficient biliary decompression, the benefit of chemotherapy is limited. As chemotherapy for unresectable biliary tract cancer, the use of gemcitabine or tegafur/gimeracil/oteracil potassium is recommended. As postoperative adjuvant chemotherapy, no effective adjuvant therapy has been established at the present time. It is recommended that further clinical trials, especially large multi-institutional RCTs (phase III studies) using novel agents such as gemcitabine should be performed as soon as possible in order to establish a standard treatment

    Measurement of the splashback feature around SZ-selected Galaxy clusters with DES, SPT, and ACT

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    We present a detection of the splashback feature around galaxy clusters selected using the Sunyaev–Zel’dovich (SZ) signal. Recent measurements of the splashback feature around optically selected galaxy clusters have found that the splashback radius, rsp, is smaller than predicted by N-body simulations. A possible explanation for this discrepancy is that rsp inferred from the observed radial distribution of galaxies is affected by selection effects related to the optical cluster-finding algorithms. We test this possibility by measuring the splashback feature in clusters selected via the SZ effect in data from the South Pole Telescope SZ survey and the Atacama Cosmology Telescope Polarimeter survey. The measurement is accomplished by correlating these cluster samples with galaxies detected in the Dark Energy Survey Year 3 data. The SZ observable used to select clusters in this analysis is expected to have a tighter correlation with halo mass and to be more immune to projection effects and aperture-induced biases, potentially ameliorating causes of systematic error for optically selected clusters. We find that the measured rsp for SZ-selected clusters is consistent with the expectations from simulations, although the small number of SZ-selected clusters makes a precise comparison difficult. In agreement with previous work, when using optically selected redMaPPer clusters with similar mass and redshift distributions, rsp is ∼2σ smaller than in the simulations. These results motivate detailed investigations of selection biases in optically selected cluster catalogues and exploration of the splashback feature around larger samples of SZ-selected clusters. Additionally, we investigate trends in the galaxy profile and splashback feature as a function of galaxy colour, finding that blue galaxies have profiles close to a power law with no discernible splashback feature, which is consistent with them being on their first infall into the cluster

    The Atacama Cosmology Telescope: A Catalog of >4000 Sunyaev–Zel’dovich Galaxy Clusters

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    We present a catalog of 4195 optically confirmed Sunyaev–Zel'dovich (SZ) selected galaxy clusters detected with signal-to-noise ratio >4 in 13,211 deg2 of sky surveyed by the Atacama Cosmology Telescope (ACT). Cluster candidates were selected by applying a multifrequency matched filter to 98 and 150 GHz maps constructed from ACT observations obtained from 2008 to 2018 and confirmed using deep, wide-area optical surveys. The clusters span the redshift range 0.04 1 clusters, and a total of 868 systems are new discoveries. Assuming an SZ signal versus mass-scaling relation calibrated from X-ray observations, the sample has a 90% completeness mass limit of M500c > 3.8 × 1014 M⊙, evaluated at z = 0.5, for clusters detected at signal-to-noise ratio >5 in maps filtered at an angular scale of 2farcm4. The survey has a large overlap with deep optical weak-lensing surveys that are being used to calibrate the SZ signal mass-scaling relation, such as the Dark Energy Survey (4566 deg2), the Hyper Suprime-Cam Subaru Strategic Program (469 deg2), and the Kilo Degree Survey (825 deg2). We highlight some noteworthy objects in the sample, including potentially projected systems, clusters with strong lensing features, clusters with active central galaxies or star formation, and systems of multiple clusters that may be physically associated. The cluster catalog will be a useful resource for future cosmological analyses and studying the evolution of the intracluster medium and galaxies in massive clusters over the past 10 Gyr

    NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

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    Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

    Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

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    This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

    Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

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    This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio
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