86,584 research outputs found
Innate mechanisms regulating peripheral B cell tolerance
No full textOur immune system protects us from invading pathogens such as bacteria, viruses, fungi and parasites. However, it can also cause disease by being improperly activated against our own tissues (autoimmune diseases) and harmless environmental factors (allergy). The immune system is built up by multiple, often overlapping, layers represented by cells and soluble factors working together to stop invading pathogens. The immune system is commonly described as being divided into a fast, more primitive, innate and a slower, more refined, adaptive part.Most often are both genetic and environmental factors affecting several parts of the immune system involved in autoimmune disease development. Thus, tolerance (related to tolerating our own tissues) is broken in patients with these diseases. The pathology associated with autoimmune disease is in general linked to the presence and activation of autoreactive B and T cells. The aim of the work presented in this thesis has been related to how certain innate mechanisms regulate autoreactive B cells.The two first papers [I, II] mainly address how increased levels of circulating apoptotic cells, evident in patients with the autoimmune disease SLE, activate autoreactive B cells. The two last papers [III, IV] relate, in a broad sense, to the splenic marginal zone (MZ) macrophage population and its function. Paper I identifies an important regulatory role for invariant natural killer T (iNKT) cells, controlling the activation of autoreactive B cells. This is dependent on a direct iNKT B cell interaction taking place before the autoreactive B cell enters a germinal center (GC). Of significance, the GC entry and subsequent autoantibody production in iNKT cell deficient mice can be limited by increasing iNKT cell levels, thus being relevant for SLE patients who have reduced levels of iNKT cells. Paper II identifies that splenic MZ macrophages with importance for tolerance bind apoptotic cells present in the circulation and that this binding involves the scavenger receptor MARCO. Furthermore, autoantibodies binding the MARCO receptor are found in SLE patients and before onset of disease in mice that develop spontaneous SLE-like disease. Paper III further addresses the role of the MARCO (macrophage) receptor and autoantibodies that bind it. The injection of an anti-MARCO antibody affected B cells and increased the production of disease-related autoantibodies following both in vivo and in vitro stimulation. The antibody-mediated MARCO engagement results in the release of soluble proinflammatory factors such as TNF-alpha. Paper IV identifies an important role for SIGN-R1, expressed on MARCO+ MZ macrophages, in the antiinflammatory affect mediated by IVIG treatment in a model of rheumatoid arthritis.In summary, these studies identify iNKT cells as a promising therapeutic target in SLE patients, MARCO as a novel autoantigen and describe a multifaceted role for the splenic MZ macrophage involved in removing apoptotic cells and (dependent on the type of stimuli) the ability to both activate and dampen the immune system. Furthermore, this thesis discusses the conflicting view of apoptotic cells as inducers of tolerance but also, during certain conditions, as activators of the immune system.List of scientific papersI. Wermeling F, Lind SM, Domange Jordö E, Cardell S, Karlsson MCI (2010). "Invariant NKT cells limit activation of autoreactive CD1d positive B cells." J. Exp. Med. [Accepted] https://doi.org/10.1084/jem.20091314 II. Wermeling F, Chen Y, Pikkarainen T, Scheynius A, Winqvist O, Izui S, Ravetch JV, Tryggvason K, Karlsson MC (2007). "Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus." J Exp Med 204(10): 2259-65. https://doi.org/10.1084/jem.20070600 III. Wermeling F, Prokopec K, Grönlund H, Karlsson MCI (2010). "MARCO engagement triggers a sterile inflammatory response with implication for autoimmune B cell activation." [Manuscript]IV. Anthony RM, Wermeling F, Karlsson MC, Ravetch JV (2008). "Identification of a receptor required for the anti-inflammatory activity of IVIG." Proc Natl Acad Sci U S A 105(50): 19571-8. https://doi.org/10.1073/pnas.0810163105 </p
Variations on the Author
No full text“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
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
Also By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation
No full textThe desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters
John F. Kennedy telegram to Roosevelt
No full textJersey Homesteads (later the Borough of Roosevelt) was established in the 1930s as an agro-industrial cooperative community. It was established specifically for urban Jewish garment workers, many of whom had emigrated from Europe. President John F. Kennedy sent a telegram to the citizens of Roosevelt, New Jersey, apologizing for not being able to attend the memorial dedication in honor of former President Franklin Delano Roosevelt. (Jersey Homesteads became Roosevelt in 1945 in honor of the president.) President Kennedy expressed his gratitude to the people of Roosevelt for constructing the memorial, and commented that it will serve as a constant reminder of Roosevelt's good works
WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function
No full textLogarithmic variance profiles and the corresponding f-1 spectra of temperature fluctuations in turbulent Rayleigh-Bénard convection
No full textWe report experimental results for the temperature variance 2(z) and the corresponding frequency spectra P(f) in turbulent Rayleigh-Bénard convection (RBC) in a cylindrical sample of aspect ratioT= D/L = 1:00 (D = 1:12 m is the diameter and L = 1:12 m the height). The measurements were conducted in the Rayleigh-number range 1011 < Ra < 1:35 1014 and Pr ' 0:8. For Ra = 1:35x1014, 2(z) could be described well by a logarithmic dependence on the vertical position z in a range of z 1 < z < z 2 with z 1 ' 70 and z 2 = 0:1L. Here L=(2Nu) is the thickness of a thin thermal sublayer adjacent to the horizontal plate where the heat flux (denoted by the Nusselt number Nu) is carried mostly by thermal diffusion. In the log layer, we found that the temperature spectra had a significant frequency range over which P(f) f with close to 1. As Ra decreased, increased so that the log layer became thinner. At Ra = 2:05 1011, z 2 < z 1 and therefore there was no range for a log layer. Correspondingly, the temperature spectrum near the horizontal plate did not have the f1 scaling form either
Maine author Franklin F. Gould recalls his first glimpse of the outside world
No full textMaine author Franklin F. Gould recalls his first glimpse of the outside world as he relates how, as a young farm boy in the late 1800\u27s, he drove his father\u27s horses on an errand to an icebound river
Mapping the Discipline of the Olympic Games An Author-Cocitation Analysis
No full textThe authors conducted an author cocitation analysis on prominent authors writing about the Olympics during the 1990s. Author cocitation is an established bibliometric technique that can be used to measure the relative similarities of topics written about by the cited authors. This enables a visual representation of the “intellectual space” of the discipline, in this case the Olympics, to be created for the period under review. So core and peripheral research areas are identified, along with their major contributors. The representation appears as a two-dimensional cluster-enhanced map. Subject expertise was then applied to the results to place labels on the generated clusters of authors and their topics
Sous-facteurs de L(F∞) d'indice 4cos2π/n,n≥3
No full textLet Q be a factor of type II1, λ a number in the Jones discrete series {4cosπ/m:m≥3}, and {ei} the Jones projections associated with λ. Denote by A2n and A1n the finite-dimensional von Neumann algebras generated, respectively, by {1,e2,⋯,en} and {1,e1,⋯,en}, with the corresponding traces. The author shows that, for n sufficiently large, the index of the inclusion An=(Q⊗A2n)∗A2nA1n⊂(Q⊗A2n+1)∗A2n+1A1n+1=An+1 is equal to λ (here ∗ denotes the reduced, amalgamated free product of the algebras in question). Using the random matrix model of Voiculescu, he proves that if Q is the von Neumann algebra L(F∞) of the free group with infinitely many generators, then An is isomorphic to L(F∞).
The two facts together imply the existence, for any λ in the Jones discrete series, of an irreducible subfactor of L(F∞) of index λ. This constitutes the first example of a nonhyperfinite, non-Γ II1 factor such that its Jones invariant is fully computable (the existence of nonirreducible subfactors of L(F∞) for any index ≥4 is a simple consequence of known results)
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