50,882 research outputs found
Rapamycin inhibits production of cytotoxic but not noncytotoxic antibodies and preferentially activates T helper 2 cells that mediate long-term survival of heart allografts in rats
No full textRapamycin (RAPA) induces unresponsiveness toward heart allografts by at least two mechanisms: selective production of noncytotoxic IgG2c-blocking Ab and preferential activation of Th2 cells. RAPA (0.8 mg/kg/day) delivered via a 14-day osmotic pump to Wistar Furth (WF; RT-1u) recipients prolongs Buffalo (BUF; RT-1b) heart allograft survival from a mean survival time (MST) of 6.5 +/- 0.5 days to 75.0 +/- 18.9 days (n = 18; p < 0.001), with 6 of 18 grafts beating for more than 100 days. Recipient sera or their IgG but not IgM fraction, obtained after postgrafting day 40, passively transfer the unresponsive state to sublethally irradiated secondary recipients in a dose-dependent and immunologically-specific fashion. Sera obtained after untreated WF hosts rejected BUF hearts contained IgG moieties of all subclasses that bound to class I MHC BUF epitopes. In contrast, the unresponsive sera contained predominantly non-C'-fixing IgG2c and only marginal amounts of activated (C') fixing IgG1, IgG2a, and IgG2b Ab. The transcription of IL-2, IL-4, and IL-10 mRNAs was assessed using a PCR method. There were similar increases in the levels of IL-2, IL-4, and IL-10 mRNA in heart allografts from both untreated and RAPA-treated recipients on day 5 postgrafting. In contrast, on days 60 and 300 postgrafting heart allografts from RAPA-treated unresponsive recipients showed increased levels of IL-10 and IL-4 but not of IL-2 mRNA, suggesting preferential activation of Th2 cells. Thus, RAPA treatment selectively inhibits the synthesis of C'-binding of IgG subclasses, spares the non C-binding blocking IgG2c Ab, and preferentially activates Th2 cells
Speculu[m] exemploru[m] ex diuersis libris in vnu[m] laboriose collectu[m].
No full textEerste blad (blanco) ontbreektThe author is probably Johannes Busch (CIBN)Titel uit incipit. Drukker en datum uit colofonBMC: Catalogue of books printed in the XVth century now in the British Museum I 226bGesamtkatalog der Wiegendrucke ; M42951Machiels, J. Catalogus van de boeken gedrukt vóór 1600 ; S 488Polain, M.-L. Catalogue des livres imprimé au 15e siècle ... ; 3574Europeana-GoogleBook
Candidate genes of Waldenström’s macroglobulinemia: current evidence and research
No full textGiada Bianchi,1 Antonio Sacco,1 Shaji Kumar,2 Giuseppe Rossi,3 Irene Ghobrial,1 Aldo Roccaro11Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 2Division of Hematology, Mayo Clinic, Rochester, MN, USA; 3Department of Hematology, Spedali Civili di Brescia, Brescia, ItalyAbstract: Waldenström’s macroglobulinemia (WM) is a relatively uncommon, indolent malignancy of immunoglobulin M-producing B cells. The World Health Organization classifies it as a lymphoplasmacytic lymphoma and patients typically present with anemia, hepatosplenomegaly and diffuse lymphadenopathies. Historically, the genetic characterization of the disease has been hampered by the relatively low proliferative rate of WM cells, thus making karyotyping challenging. The use of novel technologies such as fluorescence in situ hybridization, gene array, and whole genome sequencing has contributed greatly to establishing candidate genes in the pathophysiology of WM and to identifying potential treatment targets, such as L265P MYD88. The discovery of microRNAs and the recognition of epigenetics as a major modulatory mechanism of oncogene expression and/or oncosuppressor silencing have aided in further understanding the pathogenesis of WM. Once thought to closely resemble multiple myeloma, a cancer of terminally differentiated, immunoglobulin-secreting plasma cells, WM appears to genetically cluster with other indolent B-cell lymphomas such as chronic lymphocytic leukemia/small cell lymphoma. The relative high incidence of familial cases of WM and other B-cell malignancies has been helpful in identifying high-risk gene candidates. In this review, we focus on the established genes involved in the pathogenesis of WM, with special emphasis on the key role of derangement of the nuclear factor kappa B signaling pathway and epigenetic mechanisms.Keywords: genetics, familial cases, NF-κB, whole genome sequencing, MYD8
The long-wavelength view of GG Tau A: rocks in the ring world
No full textWe present the first detection of GG Tau A at centimetre wavelengths, made with the Arcminute Microkelvin Imager Large Array at a frequency of 16 GHz (λ = 1.8 cm). The source is detected at >6 σrms with an integrated flux density of S16GHz = 249 ± 45 µJy. We use these new centimetre-wave data, in conjunction with additional measurements compiled from the literature, to investigate the long-wavelength tail of the dust emission from this unusual protoplanetary system. We use an MCMC-based method to determine maximum likelihood parameters for a simple parametric spectral model and consider the opacity and mass of the dust contributing to the microwave emission. We derive a dust mass of Md ~ 0.1 Msun, constrain the dimensions of the emitting region and find that the opacity index at λ > 7 mm is less than unity, implying a contribution to the dust population from grains exceeding ~4 cm in size. We suggest that this indicates coagulation within the GG Tau A system has proceeded to the point where dust grains have grown to the size of small rocks with dimensions of a few centimetres. Considering the relatively young age of the GG Tau association in combination with the low derived disc mass, we suggest that this system may provide a useful test case for rapid core accretion planet formation models
Formation of Literary Image of I. M. Muravyov-Apostol
No full textThe formation of the literary image of Ivan Matveyevich Muravyov-Apostol is discussed, who entered the history of Russian literature as the author of a journalistic series “Letters from Moscow to Nizhny Novgorod” and “The Journey in Tauris in 1820.” It is noted that I. M. Muravyov-Apostol is famous for being “a scholar and lover of antiquity.” The author of the article explores the translation activity of I. M. Muravyov-Apostol, his enthusiasm for the work of the Roman poet Horace. It is shown how the translations of satirical works and odes of Horace by Muravyov-Apostol influenced the formation of his literary interests and, accordingly, the creation of the literary image of the writer. The critical works devoted to the translation activity of Muravyov-Apostol are considered. The role of friendship is noted between the writer and G. R. Derzhavin with whom they were united by similar attitude to the literary and civil issues, as well as interest in ancient culture and translation of satirical works and odic poetry of Horace. Excerpts from their correspondence are given, as well as opinions of other writers about the creative activities of Muravyov-Apostol. The author concludes that special influence on the formation of Muravyov-Apostol’s literary image had self-presentation of his translations at meetings of the society “Beseda lyubiteley russkogo slova.
Long-term wind-driven X-ray spectral variability of NGC 1365 with Swift
No full textWe present long-term (months–years) X-ray spectral variability of the Seyfert 1.8 galaxy NGC 1365 as observed by Swift, which provides well-sampled observations over a much longer time-scale (six years) and a much larger flux range than is afforded by other observatories. At very low luminosities, the spectrum is very soft, becoming rapidly harder as the luminosity increases and then, above a particular luminosity, softening again. At a given flux level, the scatter in hardness ratio is not very large, meaning that the spectral shape is largely determined by the luminosity. The spectra were therefore summed in luminosity bins and fitted with a variety of models. The best-fitting model consists of two power laws, one unabsorbed and another, more luminous, which is absorbed. In this model, we find a range of intrinsic 0.5–10.0 keV luminosities of approximately 1.1–3.5 erg s?1, and a very large range of absorbing columns, of approximately 1022–1024 cm?2. Interestingly, we find that the absorbing column decreases with increasing luminosity, but that this result is not due to changes in ionization. We suggest that these observations might be interpreted in terms of a wind model in which the launch radius varies as a function of ionizing flux and disc temperature and therefore moves out with increasing accretion rate, i.e. increasing X-ray luminosity. Thus, depending on the inclination angle of the disc relative to the observer, the absorbing column may decrease as the accretion rate goes up. The weaker, unabsorbed, component may be a scattered component from the wind
The construction of Karen Karnak: The multi-author-function
No full textThis thesis is situated within the comparatively recent developments of Web 2.0 and the emergence of interactive WikiMedia, and explores the mode of authorship within a Read/Write culture compared to that of a Read/Only tradition. The hypothesis of this study is that the role of the audience has become merged with the author, and as such, represents new functions and attributes, distinct from a more conventional concept of authorship, in which the roles of audience and author are more separate. Read/Write and participatory culture, as defined by this study, is focused on collaboration, and includes the influences of D.I.Y. culture, Open-Source practices and the production of text by multiple authors. Multi-authorship presents a re-thinking of several concepts which support the notion of the individual author, since the focus of multi-authorship is not on attribution and ownership of a finished text, but on the continued malleability of a text. Modes of multi-authorship, demonstrated in the use of the pseudonyms Alan Smithee and Karen Eliot, represent declarative authors whose names signify multiple origins, whilst concurrently indicating a distinct body of work. The function of these names form an important context to this study, since primary research involves the construction of an experimental mode of multi-authorship utilising WikiMedia technology and the interaction of thirty nine participants, who are invited to create a body of work under the collective pseudonym Karen Karnak. The data generated by this experiment is analysed using aspects of Michel Foucault's author-function to identify and determine power structures inherent in the WikiMedia context. The interplay of power structures, including concepts such as identity, ownership and the body of work, affect the resulting mode of authorship and contribute to the construction of Karen Karnak, suggesting further areas of research into the emerging multi-author
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