100,465 research outputs found
Code for the replication of the Monte Carlo analysis in Elff, Martin, Jan Paul Heisig, Merlin Schaeffer, and Susumu Shikano: "Multilevel Analysis with Few Clusters: Improving Likelihood-based Methods to Provide Unbiased Estimates and Accurate Inference"
No full textThis archive contains R and Mplus code to replicate the Monte Carlo study of ML and REML estimators and normality and t-distribution-based confidence intervals reported in our paper Elff, Martin, Jan Paul Heisig, Merlin Schaeffer, and Susumu Shikano: "Multilevel Analysis with Few Clusters: Improving Likelihood-based Methods to Provide Unbiased Estimates and Accurate Inference", British Journal of Political Science, https://doi.org/10.1017/S0007123419000097
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Charakterisierung der T-Zellantwort in der Experimentellen Autoimmunen Glomerulonephritisder Maus
No full textDie anti-glomeruläre-Basalmembran-Glomerulonephritis (anti-GBM-GN) ist eine
seltene Autoimmunerkrankung der Niere. In vielen anti-GBM-GN-Patienten zeigt sich zusätzlich eine Lungenbeteiligung, welche sich durch Lungenblutungen äußert. Wenn beide Organe betroffen sind, wird die Krankheit als Goodpasture-Syndrom bezeichnet. Unbehandelt endet die anti-GBM-GN fast immer mit dem Tod des Patienten. Der Pathomechanismus der anti-GBM-GN beruht auf der Bildung von Autoantikörpern und zusätzlich wird eine Beteiligung von T-Zellen vermutet. Die Autoimmunität richtet sich dabei gegen die Nicht-Kollagen-Domäne 1 (NC1) der α3- und α5-Kette des Typ IV Kollagens (α3(IV)NC1 und α5(IV)NC1). Autoantikörper binden an α3(IV)NC1 und α5(IV)NC1 in der Basalmembran in Niere und Lunge. In der Niere bilden sich dann typische, halbmondförmige, mononukleäre Infiltrate, die mit einer schweren Schädigung der Glomeruli und einer progressiven Niereninsuffizienz einhergehen. Demgegenüber ist die Bedeutung der T-Zellen für die Schädigung der Niere bislang unklar.
Ziel dieser Arbeit war die Etablierung eines Mausmodells für die anti-GBM-GN. In diesem Modell, der Experimentellen Autoimmunen Glomerulonephritis (EAG), sollten dann verschiedene Aspekte der Pathogenese und der Immunantwort untersucht werden. Wesentliche Punkte waren die generelle Funktion der CD4+ T-Zellen sowie die Rolle der Th17-Zellen und der regulatorischen T-Zellen. Außerdem sollte untersucht werden, ob autoreaktive T-Zellen in der Maus vorhanden sind. Die zentrale Hypothese war, dass CD4+ T-Zellen den Verlauf der Erkrankung und den damit verbundenen Nierenschaden beeinflussen. In unserem EAG-Modell wurden DBA/1J-Mäuse mit rekombinantem Human-α3(IV)NC1 einmal in komplettem und dreimal in inkomplettem Freundschen Adjuvans immunisiert. Die Mäuse entwickelten als Folge eine schwere Proteinurie und ab Woche 8 eine GN mit letalem Funktionsverlust der Niere. Nach 2 Wochen waren α3(IV)NC1-spezifische Antikörper und nach 3 - 5 Wochen IgG-Ablagerungen entlang der GBM nachweisbar. In diesem Stadium zeigten die Nieren noch keine entzündlichen Veränderungen und nur eine marginale Infiltration von Leukozyten. Erst im späten Stadium entwickelten die Tiere glomeruläre Halbmonde in der Bowman-Kapsel, erhebliche Schäden der Tubuli und eine massive Infiltration von Makrophagen. Die Infiltration von T-Zellen war weniger stark ausgeprägt und hauptsächlich im Interstitium zu beobachten. Diese T-Zellen zeigten einen aktivierten Phänotyp und enthielten einen erheblichen Anteil an Th1- und Th17-Zellen. Um die generelle Funktion der T-Zellen und deren Subpopulationen zu klären, wurden verschiedene Versuchsansätze durchgeführt. Die Depletion von CD4+ T-Zellen in der späten Phase der EAG durch einen anti-CD4-Antikörper führte zu keiner Minderung der Nierenschädigung im Vergleich zu den Kontrolltieren. Eine Neutralisierung von IL-17A über den gesamten Versuchszeitraum der EAG zeigte ebenfalls keinen veränderten Verlauf in der Nierenentzündung. Dieses Ergebnis wurde durch eine Analyse von IL-17A ko-Mäusen bestätigt. In denen wurde auch kein Unterschied im Nierenschaden beobachtet. Die Depletion von regulatorischen T-Zellen in der späten Phase der EAG hatte auch keinen Einfluss auf den Krankheitsverlauf. Im letzten Teil der Arbeit wurde versucht α3(IV)NC1-spezifische T-Zellen nachzuweisen. Nach Immunisierung konnten diese Zellen in der Milz mittels ELISpot identifiziert werden. Die Immunisierung mit einem immundominanten Peptid aus α3(IV)NC1 (P71) führte zur Induktion von P71- aber auch von α3(IV)NC1-spezifischen T-Zellen. In beiden Ansätzen waren die Frequenzen der autoreaktiven T-Zellen in der Milz sehr niedrig.
IV Zusammenfassend konnten wir das EAG-Modell etablieren und hochaktivierte T-Zellen in der Niere und α3(IV)NC1-spezifische T-Zellen in der Milz nachweisen. Um die Funktion der T-Zellen in der anti-GBM-GN zu klären, sind weitere Studien notwendig.Anti-glomerular basement membrane (GBM) glomerulonephritis (GN) is a rare autoimmune kidney disease. This GN is often accompanied by lung haemorrhage and then commonly referred to as Goodpasture’s syndrome. Untreated, anti-GBM-GN is usually fatal for the patient. The formation of autoantibodies is considered to be the central pathomechanism of anti-GBM-GN. However, there is also evidence for the participation of T cells. Autoimmunity is directed against the noncollagen domain 1 (NC1) of the α3 and α5 chain from type IV collagen (α3(IV)NC1 and α5(IV)NC1). Autoantibodies bind to the α3(IV)NC1 and α5(IV)NC1 within the basement membrane in kidney and lung. In the kidney, this is followed by massive immune cell infiltration and glomerular crescent formation, indicating a severe and rapidly progressing injury. The function of T cells for renal damage is so far unclear.
The major aim of this work was the establishment of a mouse model for anti-GBM-GN. In this model, the experimental autoimmune glomerulonephritis (EAG), different aspects of the pathogenesis of the disease and the immune response within the kidney should be examined.
Central topics of research were the general function of the CD4+ T cells as well as the role of Th17 cells and regulatory T cells in progression of renal destruction. In addition, it should be examined whether T cells specific for peptide derived from the basement membrane could be identified in the mouse. The central hypothesis was that CD4+ Tcells affect progression of the disease and control renal damage. In our EAG model, DBA/1J mice were immunized with recombinant human α3(IV)NC1 in complete Freund’s adjuvant and boosted three times with human α3(IV)NC1 in incomplete Freund’s adjuvant. As consequence, mice developed a severe proteinuria and starting from week 8, a glomerulonephritis with fatal loss of kidney function. After 2 weeks, α3(IV)NC1-specific antibodies were detectable, and after 3 - 5 weeks mice displayed IgG deposits along the GBM. However, at this stage the kidneys showed only marginal infiltration of leukocytes and limited signs of inflammation. Only in the late stage, the animals developed glomerular crescents in the Bowman’s capsule, extensive tubulointerstitial damage and massive infiltration of macrophages. Infiltration of T cells was less pronounced and mainly observed in the interstitium. These T cells showed an activated phenotype and contained a substantial portion of Th1 and Th17 cells. To clarify the general function of T cells and of their subpopulations, different experiments were performed. The depletion of CD4+ T cells in the late phase of EAG by an anti-CD4 antibody did not cause a reduction of kidney damage compared with control animals. Neutralization of IL-17A during the whole immunization and observation period of EAG showed likewise no alteration in the kidney inflammation. This result was confirmed by an analysis of IL-17A ko mice, in which also no difference in the kidney damage was observed. The depletion of regulatory T cells in the late phase of EAG had also no influence on disease progression. In the last part of the work, we tried to identify α3(IV)NC1-specific T cells in immunized mice. Using IFNγ-ELISpot, cells were detected in the spleen of mice immunized with α3(IV)NC1. The immunization with an immune-dominant peptide derived from α3(IV)NC1 (P71) led to the induction of P71- and α3IVNC1-specific T cells. In both approaches, frequencies of the autoreactive T cells in the spleen were however very low. In summary, we could establish the EAG model and identify highly activated T cells in the kidney and α3(IV)NC1-specific T cells in the spleen. The funtion of T cells in the anti-GBMGN could not be revealed so far, therefore, further studies are necessary
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
Indirect dark-matter detection with MadDM v3.2 -- Lines and Loops
No full textAutomated tools for the computation of particle physics' processes have
become the backbone of phenomenological studies beyond the standard model.
Here, we present MadDM v3.2. This release enables the fully automated
computation of loop-induced dark-matter annihilation processes, relevant for
indirect detection observables. Special emphasis lies on the annihilation into
, where or any new particle even under the dark
symmetry. These processes lead to the sharp spectral feature of monochromatic
gamma lines -- a smoking-gun signature of dark matter in our Galaxy. MadDM
provides the predictions for the respective fluxes near-Earth and derives
constraints from the gamma-ray line searches by Fermi-LAT and HESS. As an
application, we discuss the implications for the viable parameter space of a
top-philic -channel mediator model and the inert doublet model.Comment: 21 pages + references; Minor changes in presentation, references
added, matches journal versio
Measuring industry-science links through inventor-author relations: A profiling method
No full textIn this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;
Wave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
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