1,720,983 research outputs found

    Transforming growth factor-β signaling in thymic epithelial cells : its role in development, steady-state and immune reconstitution

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    The thymus constitutes the primary lymphoid organ responsible for the generation of naïve T cells. Its stromal compartment is composed of a scaffold of different subsets of epithelial cells that provide soluble and membrane-bound molecules essential for thymocyte maturation and selection. With senescence, a steady decline in the thymic output of T cells has been observed. Numeric and qualitative changes in the stromal compartment of the thymus resulting in reduced thymopoietic capacity have been suggested to account for this physiological process. The precise cellular and molecular mechanisms underlying thymic senescence are, however, only incompletely understood. Here, we demonstrate that TGF-beta signaling in thymic epithelial cells exerts a direct influence on the cell’s capacity to support thymopoiesis in the aged mouse as the physiological process of thymic senescence is mitigated in mice deficient for the expression of TGF-beta receptor type II on thymic epithelial cells. Moreover, TGF-beta signaling in these stromal cells transiently hinders the early phase of thymic reconstitution following myeloablative conditioning and hematopoietic stem cell transplantation. Hence, inhibition of TGF-beta signaling decelerates the process of age-related thymic involution and may hasten the reconstitution of regular thymopoiesis following hematopoietic stem cell transplantation

    Angeborene Immundefekte mit vorwiegender Störung der Antikörperproduktion

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    Angeborene Immundefekte, welche überwiegend mit einer quantitativ oder funktionell eingeschränkten Antikörperantwort einhergehen (Antikörperdefekte), zählen zu den häufigsten Formen primärer Immundefizienz mit einer geschätzten Inzidenz zwischen 1:400 und 1:100.000. Gemäß der aktualisierten Klassifizierung der IUIS (International Union of Immunological Societies) werden diese Störungen in 4 verschiedenen Untergruppen eingeteilt, basierend v. a. auf der Ausprägung des Antikörpermangels sowie nummerischer Veränderungen der B-Zellen. Antikörper-Defekte sind durch Störungen der B-Zell-Entwicklung im Knochenmark bzw. durch Einschränkung der Proliferation, Differenzierung oder Ausreifung von B-Zellen verursacht. Patienten mit Antikörperdefekten leiden typischerweise unter rezidivierenden Infektionen, welche in der Regel durch (kapseltragende) Bakterien, wie z. B. H. influenzae oder S. pneumoniae, verursacht werden. Charakteristischerweise kommt es bei betroffenen Patienten zu sogenannten Schleimhaut-assoziierten Infektionen, wie Otitiden, Pneumonien und bei älteren Patienten auch Sinusitiden. Die Therapie besteht in einer frühzeitigen und konsequenten Therapie von Infektionen und bei schweren Verlaufsformen in der regelmäßigen prophylaktischen Gabe von intravenös oder subkutan verabreichten Immunglobulinen vom Typ G (IgG)

    Physiologie der B- und T-Lymphozyten

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    Das adaptive Immunsystem bestehend aus T- und B-Zellen ist für die Abwehr einer Vielzahl von Viren, Bakterien und Pilzen unabdingbar. Zudem werden transformierte körpereigene Zellen erkannt und eliminiert. Im Rahmen der Entwicklung dieser Zellen werden bestimmte Gensequenzen der entsprechenden Rezeptoren umgelagert, um eine hohe Variabilität der T- und B-Zell-Rezeptorspezifitäten zu erzielen. Interaktionen der sich entwickelnden Immunzellen mit ihrer Umgebung sorgen dafür, dass potenziell autoreaktive Spezifitäten eliminiert werden. Zudem vermögen regulatorische Subpopulationen von B- und T-Zellen Effektorzellen zu unterdrücken, um Schaden der körpereigenen Zellen zu limitieren. Dieses Kapitel gibt eine Übersicht über die normale Entwicklung und Funktion der T- und B-Zellen

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dynamics of recent thymic emigrants in pediatric recipients of allogeneic hematopoetic stem cell transplantation

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    After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the recurrence of recent thymic emigrants (RTE) and self-tolerant T cells indicate normalized thymic function. From 2008 to 2019, we retrospectively analyzed the RTE-reconstitution rate and the minimal time to reach normal age-specific first percentiles for CD31+CD45RA+CD4+T cells in 199 pediatric patients after allo-HSCT for various malignant and non-malignant diseases. The impact of clinically significant graft-versus-host disease (GvHD), age at transplantation, underlying disease and cumulative area under the curve of busulfan on RTE-reemergence was assessed in multivariable longitudinal analysis. RTE-reconstitution (coefficient −0.24, 95% CI −0.33 to −0.14, p < 0.001) was slowed down by GvHD and the time to reach P1 was significantly longer (Event Time Ratio 1.49, 95% CI 1.25 to 1.78, p < 0.001). Older age at transplantation was also associated with a slower RTE-reconstitution (coefficient −0.028, 95% CI −0.04 to −0.02, p < 0.001) and time to reach P1 was significantly longer (Event Time Ratio 1.03, 95% CI 1.02 to 1.05, p < 0.001). RTE-reconstitution velocity was not influenced by underlying disease or cumulative busulfan exposure. In summary, duration until thymic reactivation was independent of both conditioning intensity and underlying disease and was negatively influenced by older age and GvHD

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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