139,515 research outputs found

    PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells.

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    During humoral immune responses, two distinct genetic modification events diversify the Ig genes in germinal center (GC) B cells: somatic hypermutation and class switch recombination (CSR). Both processes require the activity of activation-induced cytidine deaminase (AID), an enzyme expressed specifically in GC B cells. However, the mechanisms that regulate AID activity are largely unknown. Here we report that protein kinase A (PKA) phosphorylates AID and regulates its activity in GC B cells. AID physically interacts with the PKA holoenzyme in the cytoplasm and is phosphorylated by the PKA catalytic subunit at specific residues. AID phosphorylation is required for CSR, because substitution of the two phosphorylation targets impairs its ability to rescue CSR in AID-deficient B cells. Pharmacologic inhibition of PKA prevents isotype class switching in a murine B-cell lymphoma cell line; conversely, B cells from mice where PKA activity is made constitutive by conditional deletion of the PKA regulatory subunit gene display enhanced CSR. These findings implicate PKA in the regulation of AID function and suggest that the control of T cell-dependent immune responses may be modulated, via AID, by signals that activate PKA

    Testing spectral models for stellar populations with star clusters – II. Results

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    20 pages, 16 figures, 8 tables.-- Articles online in advance of print.-- Pre-print archive.High spectral resolution evolutionary synthesis models have become a routinely used ingredient in extragalactic work, and as such deserve thorough testing. Star clusters are ideal laboratories for such tests. This paper applies the spectral fitting methodology outlined in Paper I to a sample of clusters, mainly from the Magellanic Clouds and spanning a wide range in age and metallicity, fitting their integrated light spectra with a suite of modern evolutionary synthesis models for single stellar population. The combinations of model plus spectral library employed in this investigation are Galaxev/STELIB, Vazdekis/MILES, SED@/GRANADA, and Galaxev/MILES+GRANADA, which provide a representative sample of models currently available for spectral fitting work. A series of empirical tests are performed with these models, comparing the quality of the spectral fits and the values of age, metallicity and extinction obtained with each of them. A comparison is also made between the properties derived from these spectral fits and literature data on these nearby, well studied clusters. These comparisons are done with the general goal of providing useful feedback for model makers, as well as guidance to the users of such models. We find that new generation of models using the GRANADA and MILES libraries are superior to STELIB-based models both in terms of spectral fit quality and regarding the accuracy with which age and metallicity are retrieved. Accuracies of about 0.1 dex in age and 0.3 dex in metallicity can be achieved as long as the models are not extrapolated beyond their expected range of validity.This work has been funded with support from the Spanish Ministerio de Educación y Ciencia through the grants AYA2007-64712, and cofinanced with FEDER funds. We also thank support from a joint CNPq-CSIC bilateral collaboration grant.Peer reviewe

    Spatially-localized time dependent solutions including turbulence and their interactions in 2D Kolmogorov flow

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    In 2D Kolmogorov flow in small aspect ratio domains, spatially-localized solutions such as kink, traveling or time-dependent kink-antikink pars coexist. However, the conservation of the flow rate in the y direction strongly restrict combination of localized solutions and their positioning. We find that by adding a homogeneous flow U y their positioning is controlled and each of localized solutions including a spatially-localized chaos is isolated. Numerical results suggest that these isolated solutions can be elements constructing a whole flow

    Transformation of ionic liquid into carbon nanotubes in confined nanospace

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    We have developed a two-step filling process for the nano-reaction of ionic liquid in a tip-closed SWNT, where fullerenes are inserted at the end of the host SWNT as a plug to prevent the leakage of the confined ionic liquid during heat treatment

    Characteristics of overlap region in high-Reynolds number turbulent channel flow

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    Direct numerical simulation of the fully developed turbulent channel flows have been carried out at the Reynolds number based on the friction velocity and the channel half width, 2000, 4000 and 8000. A hybrid 10th order accurate finite difference scheme in the stream and spanwise directions, and a second-order scheme in the wall-normal direction is adapted as the spatial discretization method. We observed the plateau profiles in the indicator function corresponded to the von Karman constant. Furthermore, second peak of streamwise pre-multiplied spectra were appeared in the same wall normal height, 300 < y+ < 600, in case of Re = 4000. Nevertheless, the effects of the lager than the channel half height scale on the streamwise turbulent intensity are fixed contributions without dependence on Reynolds number. These results suggested that the new streamwise vortexes are formed between buffer layer and outer layer with increasing of Reynolds number

    La 'circunstancia' de 'Herederos y Pretendientes

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    In June 2010, the Ortega y Gasset Foundation hosted a Conference about the “Spanish Philosophical Transition” in order to debate the book of Francisco Vázquez, La filosofía española. Herederos y Pretendientes. Una lectura sociológica (1963-1990), recently published. This paper is the author’s response to criticism raised in the Conference and to published reviews received by this book. First, the author summarized the argument of Herederos y pretendientes. Secondly he responds and takes into account the most important objections against the book’s hypothesis and methodology. Finally the author evaluates the favorable judgments received by the book and suggests the limits of the historian’s task.Fundación Ortega y Gasset-Marañó

    Author self-citation in orthodontics is associated with author origin and gender.

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    BACKGROUND The aims of this bibliometric study were to determine author self-citation trends in high-impact orthodontic literature and to investigate possible association between self-citation and publication characteristics. METHODS Six orthodontic journals with the highest impact factor as ranked by 2017 Journal Citation Reports were screened for a full publication year (2018) for original research articles, reviews, and case reports. Eligible articles were scrutinized for article and author characteristics and citation metrics. Univariable and multivariable negative binomial regression was used to examine associations between self-citation incidence and publication characteristics. RESULTS Medians for author self-citation rate of the most self-citing authors and self-citations were 3.03% (range 0-50) and 1 (range 0-19), respectively. In the univariable analysis, there was no association between self-citation counts and study type (P = 0.41), article topic (P = 0.61), number of authors (P = 0.62), and rank of authors (P = 0.56). Author origin (P = 0.001), gender (P = 0.001) and journal (P = 0.05) were associated with self-citation counts and in the multivariable analysis only origin and gender remained strong self-citation predictors. Asian authors and females self-cited significantly less often than all other regions and male authors. CONCLUSIONS Authors in orthodontics do not self-cite at a frequency that suggests potential citation manipulation. Author origin and gender were the only variables associated with citations counts. More bibliometric research is necessary to draw solid conclusions about author self-citation trends in orthodontic literature

    Vista y plano de Toledo

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    In View and plan of Toledo, a faithful representation of the city and homage to it, the vision of the Virgin as well as the nude on the left, allegory of the river Tagus, sustenance of the life of the region represented by the youth clothed in olive-green, all are casual images presented in the sky, on the earth and in the thicket. El Greco’s imagination operates with almost mathematical rigour. A genealogical link can be traced between Jesus’ tunic in the Modena-Triptych, the tunic of the kneeled angel of the Baptism of the Prado and the chasuble carried by the Virgin in Vista y plano. The composition of the picture is related to the Adoration of the first period, repeating the youth with the map the same role of Saint Jerome with the Vulgata.En Vista y plano de Toledo, que es fiel retrato y homenaje a la ciudad, tanto la visión de la Virgen como el desnudo de la izquierda, alegoría del río Tajo, sustento básico para la vida de la región representada por el joven de la derecha, son imágenes casuales aparecidas en el cielo, en la tierra y en los matorrales. La fantasía grequiana opera con un rigor casi matemático. Se observa una genealogía establecida entre la túnica de Jesús del Tríptico de Módena, la del ángel arrodillado del Bautismo del Prado y la casulla portada por la Virgen en Vista y plano. La composición de Vista y plano está relacionada con la Adoración de la primera época toledana, estableciendo un vínculo entre el joven con el plano y san Jerónimo con la Vulgata

    Overview of the Author Profiling Task at PAN 2013

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    [EN] This overview presents the framework and results for the Author Profiling task at PAN 2013. We describe in detail the corpus and its characteristics, and the evaluation framework we used to measure the participants performance to solve the problem of identifying age and gender from anonymous texts. Finally, the approaches of the 21 participants and their results are described.The author profiling task @PAN-2013 was an activity of the WIQ-EI IRSES project (Grant No. 269180) within the FP 7 Marie Curie People Framework of the European Commission. We want to thank the Forensic Lab of the Universitat Pompeu Fabra Barcelona for sponsoring the award for the winner team. The work of the first author was partially funded by Autoritas Consulting SA and by Ministerio de Economía y Competitividad de España under grant ECOPORTUNITY IPT-2012-1220-430000. The work of the second author was in the framework the DIANA-APPLICATIONS-Finding Hidden Knowledge in Texts: Applications (TIN2012-38603-C02-01) project, and the VLC/CAMPUS Microcluster on Multimodal Interaction in Intelligent Systems. The work of fifth author was funded in part by the Swiss National Science Foundation (SNF) project "Mining Conversational Content for Topic Modelling and Author Identification (ChatMiner)" under grant number 200021_130208.Rangel, F.; Rosso, P.; Koppel, M.; Stamatatos, E.; Inches, G. (2013). Overview of the Author Profiling Task at PAN 2013. CLEF Conference on Multilingual and Multimodal Information Access Evaluation. 352-365. https://riunet.upv.es/handle/10251/46636S35236

    Author Co-Citation Analysis (ACA): a powerful tool for representing implicit knowledge of scholar knowledge workers

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    In the last decade, knowledge has emerged as one of the most important and valuable organizational assets. Gradually this importance caused to emergence of new discipline entitled ―knowledge management‖. However one of the major challenges of knowledge management is conversion implicit or tacit knowledge to explicit knowledge. Thus Making knowledge visible so that it can be better accessed, discussed, valued or generally managed is a long-standing objective in knowledge management. Accordingly in this paper author co- citation analysis (ACA) will be proposed as an efficient technique of knowledge visualization in academia (Scholar knowledge workers)
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