101,046 research outputs found
Soziale Ausschließung und die nicht gänzlich gelingende Enteignung moralischer Empörung über Ungerechtigkeit
No full textBöhnisch T, Cremer-Schäfer H. Soziale Ausschließung und die nicht gänzlich gelingende Enteignung moralischer Empörung über Ungerechtigkeit. In: Althoff M, ed. Zwischen Anomie und Inszenierung. Interpretationen der Entwicklung der Kriminalität und der sozialen Kontrolle. Baden-Baden: Nomos; 2004: 167-186
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Verborgene und unbewusste Dynamiken in Organisationen: Systeme psychoanalytisch verstehen in Beratung, Coaching und Supervision.
No full textAlthoff M, Bredemann M, Heitmann T, Kröhnert S. Verborgene und unbewusste Dynamiken in Organisationen: Systeme psychoanalytisch verstehen in Beratung, Coaching und Supervision. FoRuM Supervision - Zeitschrift für Beratungswissenschaft und Supervision. 2024;32(63):171–180
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
Verbesserung der adoptiven T-Zell-Therapie durch die T-Zell-spezifische Blockade hemmender T-Zell-Rezeptoren anstelle einer systemischen Antikörperbehandlung
No full textImmunotherapy has become an important and established pillar within cancer therapy. This form of therapy is based on the body's own immune cells, including T and B cells, which recognize and fight foreign structures arising from abnormal development of cancer cells, among others. In adoptive T cell therapy (ATT), a special form of immunotherapy, tumor-specific T cells are expanded in vitro and then transferred into the patient. In the course of cancer, the tumor cells may no longer be recognized or the tumor environment may have an inhibitory effect on the T cells. One mechanism of mediating T cell inhibition, is the binding of T cell inhibitory receptors (TIRs), such as PD-1, TIM-3 and LAG-3, to their cognate ligands. This T-cell brake should be released by blocking the binding with antagonistic antibodies. Although this therapeutic approach can be very successful, not all patients respond to the therapy and severe side effects may occur, especially upon combination of several antibodies.
To reduce side effects while maintaining therapeutic efficacy, this project tested the possibility of multiple genetic editing of murine T cells, “bulk” - without prior dilution to single cells . using CRISPR/Cas9 leading to greatly reduced expression of the TIRs PD-1, TIM-3 and LAG-3.
Initially, CD4+ and CD8+ T cell responses against tumor cells were comparatively examined in the context of model elucidation, in vitro and in vivo. In vitro cytotoxicity and cytokine production and in vivo tumor local and peripheral antigen-specific T cell responses were analyzed.
After successful optimization and analysis of the tumor model, T cells were genetically edited using CRISPR/Cas9. The best CRISPR ribonucleic acid (crRNA) sequences for each TIR-encoding gene was determined and the molecular evidence of editing was obtained in a murine lymphoma cell line. Subsequently, multiple editing was successfully demonstrated in primary murine T cells.
The genetically edited T cells were then tested in vivo in comparison to non-edited T cells and showed a better anti-tumor response. Afterwards, the edited T cells were compared with the previously established combinatorial approach of ATT and antibody administration. Thereby, the edited T cells showed an intermediate anti-tumor response with respect to the comparison groups with non-edited T cells in ATT and the combinatorial approach.Die Immuntherapie ist eine wichtige und etablierte Form der Krebstherapie. Sie basiert auf körpereigenen Immunzellen, wie zum Beispiel T- und B-Zellen, die fremdartige Strukturen erkennen und bekämpfen. Diese fremden Strukturen können unter anderem durch eine abnorme Entwicklung von Krebszellen entstehen. Werden Zellen, die sich dereguliert teilen nicht von Immunzellen erkannt und eliminiert, entsteht Krebs. Bei der adoptiven T-Zelltherapie (ATT), einer speziellen Form der Immuntherapie, werden tumorspezifische T-Zellen in vitro expandiert und dann in den Patienten transferiert. Im Verlauf einer Krebserkrankung kann es dazu kommen, dass die Tumorzellen nicht mehr erkannt werden können oder die Tumorumgebung hemmend auf die T-Zellen wirkt. Die Hemmung der T-Zellen kann unter anderem durch die Bindung sogenannter T-Zell-inhibierender Rezeptoren (TIRs) wie PD-1, TIM-3 und LAG-3, mit deren jeweiligen Liganden vermittelt werden. Diese T-Zell-Hemmung soll durch antagonistische Antikörper blockiert werden. Obwohl dieser therapeutische Ansatz teilweise sehr erfolgreich ist, sprechen nicht alle Patienten auf die Therapie an und es können, insbesondere bei Kombination mehrerer blockierender Antikörper, starke Nebenwirkungen auftreten.
Um die Nebenwirkungen zu reduzieren und dabei den therapeutischen Erfolg der Therapie zu erhalten, wurde in dieser Arbeit die Möglichkeit getestet, murine T-Zellen, „bulk“ - ohne vorherige Vereinzelung - mittels CRISPR/Cas9 mehrfach genetisch zu editieren, sodass diese Zellen die TIRs PD-1, TIM-3 und LAG-3 weniger stark exprimieren.
Zunächst wurden im Rahmen der Modeletablierung, in vitro und in vivo die CD4+ und CD8+ T-Zell-Antworten gegen Tumorzellen vergleichend untersucht. Nach erfolgreicher Optimierung und Analyse des Tumormodells, wurden die T-Zellen mittels CRISPR/Cas9 genetisch editiert. Die besten CRISPR ribonucleic acid (crRNA) Sequenzen für die jeweiligen TIR codierenden Gene wurden ermittelt und der molekulare Nachweis der Editierung erfolgte in einer murinen Lymphomzelllinie. Es konnte erfolgreich in primären murinen T-Zellen die Mehrfacheditierung gezeigt werden.
Die editierten T-Zellen wurden daraufhin in vivo im Vergleich zu nicht editierten T-Zellen getestet und zeigten dort eine bessere Anti-Tumor-Antwort. Im Vergleich mit dem zuvor im Modell etablierten, kombinatorischen Ansatz von ATT und Antikörpergabe zeigten die editierten T-Zellen eine intermediäre anti-Tumorantwort, bezugnehmend auf die Vergleichsgruppen mit nicht editierten T-Zellen im ATT und dem kombinatorischen Ansatz
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
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;
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