2,915 research outputs found
Interdisciplinary characterization of T cell dynamics in HIV infection
No full textHIV has caused one of the most devastating pandemics in modern medicine. HIV infects and kills on of the central players in effector immunity, CD4+ T cells, that provide helper mechanisms to all arms of the immune system. Although the virus indirectly affects most cells of the immune system, CD4+ and CD8+ T cells in particular become highly dysfunctional and show traits of severe immune pathology during the infection. These cells are of importance in adaptive immunity and recognize through their T cell receptors foreign antigens that are presented on MHC molecules. In the absence of normal T cell dynamics and homeostasis, host effector immunity collapses and most individuals develop AIDS, without antiretroviral therapy.The growing number of immunological variables measured today poses challenges to studying T cell dynamics in HIV infection. However, with the introduction of new techniques within bioinformatics, we now possess statistical tools to analyse combined measurements of T cell pathology, epitope targeting and dysfunction in the context of HIV infection. In all of these studies, multi-parametric flow cytometry and advanced bioinformatics were thus combined to study traits of T cell dynamics in HIV infection. By examining a broad range of T cell markers, we concluded in paper I that the CD4/CD8 ratio correlated with a significantly increased number of pathological T cell populations and was associated with CD4 recovery 2 years after ART initiation. These data indicate that the CD4/CD8 ratio would be a suitable clinical predictor of combined T cell pathology in HIV infection.By developing a novel epitope selection algorithm in paper II, we aimed to identify optimal MHC class II-restricted HIV epitopes with broad viral and host coverage. Employing both immunological and virological approaches, a set of peptides was shown to induce broad HIV-specific CD4+ T cell responses, where the number of targeted Gag epitopes was inversely correlated with HIV viral load. In order to further trace events of HIV disease progression, we investigated whether the combined pattern of HIV evolution and CD8+ T cell functionality could explain the risk of HIV disease progression in HLA-B*5701+ patients (paper III). HIV Gag sequence diversity was shown to be lower and multi-functional responses higher against wild-type and autologous HLA-B*5701-restricted epitopes in subjects of low risk of disease progression. Both of these studies highlight the power of multidisciplinary approaches, integrating complex evolutionary and immunological data, to understand the mechanisms underlying T cell dysfunction and pathogenesis.To further clarify why HIV-specific CD8+ T cells exhibit severe dysfunctionalcharacteristics in both treated and untreated HIV infection, we studied in paper IV the role of two central T-box transcription factors (T-bet and Eomes) using combined flow cytometry and bioinformatics. It was shown that HIV-specific CD8+ T cells almost exclusively have highly elevated levels of Eomes, but lower T-bet expression, which is associated with up-regulation of numerous inhibitory receptors, impaired functional characteristics and a transitional memory differentiation status. Surprisingly, these features were retrained despite any years on ART, implicating that the relationship between T-bet and Eomes might partly explain the inability of CD8+ T cells to control viral rebound post ART cessation.In summary, this thesis has combined the knowledge of immunology andvirology with the help of bioinformatics to study T cell dynamics in HIV infection. This interdisciplinary approach has increased our knowledge of factors that are linkedto T cell pathology, risk of disease progression and impaired T cell functionality.List of scientific papersI. Marcus Buggert, Juliet Frederiksen, Kajsa Noyan, Jenny Svärd, Babilonia Barqasho, Anders Sönnerborg, Ole Lund, Piotr Nowak, Annika C. Karlsson. Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection. J Immunol. 2014, 192. Feb 3 [Epub ahead of print]. https://doi.org/10.4049/jimmunol.1302596. II. Marcus Buggert, Melissa Norström, Chris Czarnecki, Emmanuel Tupin, Ma Luo, Katarina Gyllensten, Anders Sönnerborg, Claus Lundegaard, Ole Lund, Morten Nielsen, Annika C Karlsson. Characterization of HIV-Specific CD4+ T Cell Responses against Peptides Selected with Broad Population and Pathogen Coverage. PLoS One. 2012;7(7):e39874. https://doi.org/10.1371/journal.pone.0039874. III. Melissa M Norström, Marcus Buggert, Johanna Tauriainen, Wendy Hartogensis, Mattia C Prosperi, Mark A Wallet, Frederick Hecht, Marco Salemi, Annika C Karlsson. Combination of immune and viral factors distinguish low-risk versus high-risk HIV-1 disease progression in HLAB* 5701 subjects. J Virol. 2012 Sep;86(18):9802-16. https://doi.org/10.1128/JVI.01165-12 IV. Marcus Buggert, Johanna Tauriainen, Takuya Yamamoto, Juliet Frederiksen, Martin Ivarsson, Jacob Michaelsson, Ole Lund, Bo Hejdeman, Marianne Jansson, Anders Sönnerborg, Richard A. Koup, Michael R. Betts, Annika C. Karlsson. T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection. [Manuscript]</p
Marcus Joseph Wright memoirs, MSS.1585
No full textAbstract: An incomplete typescript copy (18 pp.) of, "Memoirs of Brigadier General Marcus J. Wright, CSA."Scope and Content Note: The collection contains an incomplete typescript copy (18 pp.) of, "Memoirs of Brigadier General Marcus J. Wright, CSA," which includes a family genealogy, and accounts of his early life in Tennessee and his career.Biographical/Historical Note: Confederate General and author from Tennessee
Marcus on Belief and Belief in the Impossible
No full textI review but don’t endorse Marcus’ arguments that impossible beliefs are impossible. I defend her claim that belief’s objects are, in some important sense, not the bearers of truth and falsity, discuss her dispositionalism about belief, and argue it’s a good fit with the idea that belief’s objects are Russellian states of affairs.
Reviso, pero no suscribo, los argumentos de Marcus a favor de que las creencias imposibles son imposibles.
Defiendo su tesis de que los objetos de las creencias no son, en algún sentido importante, los soportes
de la verdad y la falsedad; discuto su disposicionalismo acerca de las creencias y argumento que encaja bien
con la idea de que los objetos de las creencias son estados de cosas russellianos
Marcus Aurelius
No full textBy John Sellars Author: SELLARS, John. Reader in Philosophy, Royal Holloway University of London Reference: Marcus Aurelius. Abingdon: Routledge, 2020, x + 146 pp., ISBN 9780367146078 In this new study, John Sellars offers a fresh examination of Marcus Aurelius’ Meditations as a work of philosophy by placing it against the background of the tradition of Stoic philosophy to which Marcus was committed. The Meditations of Marcus Aurelius is a perennial bestseller, attracting countless..
Ben Marcus, 19th Annual ODU Literary Festival
No full textBen Marcus is the author of The Age of Wire and String, published recently by Alfred A. Knopf. His short fiction has appeared in Grand Street, The Iowa Review, The Pushcart Prize Anthology, The Mississippi Review, The Quarterly, Conjunctions, and Story Quarterly. He was born in Chicago in 1967 and grew up in the Midwest and in Europe, New York and Texas. His undergraduate degree was earned in philosophy at New York University. He received an M.F.A. from Brown University, and has since taught writing in New York, Texas, and Virginia. He is a senior editor of the literary journal Conjunctions, and will present a section of new fiction chosen for the spring issue, Sticks and Stones. Presently he lives in Virginia, where he is an assistant professor at Old Dominion University
Portrait of Marcus Bach
No full textPortrait depicts Marcus Bach, noted author and philosopher and educator of religious studies
Stanley Marcus
No full textStanley Marcus (April 20, 1905 – January 22, 2002) was an early president (1950–1972) and later chairman of the board (1972–1976) of the luxury retailer Neiman Marcus in Dallas, Texas, which his father and aunt had founded in 1907. During his tenure at the company, he also became a published author, writing his memoir Minding the Store and also a regular column in The Dallas Morning News. Awards- the Chevalier Award from the French Legion of Honor listed in the Houston Chronicle\u27s list of the 100 most important Texans. He was named by Harvard Business School among the greatest American Business Leaders of the 20th century.https://nsuworks.nova.edu/nsudigital_forums/1086/thumbnail.jp
Virilization and Enlarged Ovaries in a Postmenopausal Woman
No full textA patient with postmenopausal bleeding and virilization was found to have bilaterally enlarged ovaries with a yellow cut surface. Histology revealed cortical stromal hyperplasia with stromal hyperthecosis. This hyperplastic condition should not be mistaken for an ovarian neoplasm.Peer reviewe
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