10509 research outputs found
Sort by
Responsible Use – The Social License-to-Operate:A business approach towards sustainability in chemicals & materials
No full textRhetorik
No full textSowohl das Recht als auch die Literatur sind sprachlich verfasst. Als rhetorisch ist die adressaten- und wirkungsbezogene Geformtheit von Rechtstexten und literarischen Texten zu beschreiben. Dabei umfasst 'Rhetorik' mehr als den Einsatz bestimmter 'rhetorischer Mittel' (Elocutio-Rhetorik). Wie gerade die sog. 'neue Rhetorik' im Anschluss an Aristoteles geltend gemacht hat, ist die Argumentation wesentliches Element der rhetorischen Kommunikation. Zugriffsweisen auf die Rhetorik unterscheiden sich historisch, kulturell und bezüglich ihrer epistemischen Funktion. Daher argumentiert die neuere Rhetorik-Forschung dafür, rhetorische Produktion geschehensorientiert zu untersuchen und dabei ihrer Geschichtlichkeit Rechnung zu tragen. Der vorliegende Artikel gibt keinen allumfassenden Überblick, sondern fokussiert auf die Rhetorik im Recht und in der Literatur sowie auf rhetorische Dimensionen des Verhältnisses von Recht und Literatur.Both law and literature are composed of language. The forming of legal and literary texts according to their recipients and effects can be described as rhetoric. In this sense, 'rhetoric' includes more than the use of certain rhetorical devices (elocutio rhetoric). Especially as the so-called 'new rhetoric' has asserted following Aristotle, argumentation is a central element of rhetorical communication. Modes of access to rhetoric differ historically, culturally and in relation to their epistemic function. Therefore, newer research on rhetoric argues in favour of analysing rhetorical production as it occurs and at the same time accounting for its historicity. This article does not provide an all-encompassing overview, but focuses on rhetoric in law and in literature as well as on the rhetorical dimensions of the relationship between law and literature
The Emerging Role of uORF-Encoded uPeptides and HLA uLigands in Cellular and Tumor Biology
No full textRecent technological advances have facilitated the detection of numerous non-canonical human peptides derived from regulatory regions of mRNAs, long non-coding RNAs, and other cryptic transcripts. In this review, we first give an overview of the classification of these novel peptides and summarize recent improvements in their annotation and detection by ribosome profiling, mass
spectrometry, and individual experimental analysis. A large fraction of the novel peptides originates from translation at upstream open reading frames (uORFs) that are located within the transcript leader sequence of regular mRNA. In humans, uORF-encoded peptides (uPeptides) have been detected in both healthy and malignantly transformed cells and emerge as important regulators in cellular and immunological pathways. In the second part of the review, we focus on various functional implications of uPeptides. As uPeptides frequently act at the transition of
translational regulation and individual peptide function, we describe the mechanistic modes of translational regulation through ribosome stalling, the involvement in cellular programs through protein interaction and complex formation, and their role within the human leukocyte antigen (HLA)-associated immunopeptidome as HLA uLigands. We delineate how malignant transformation may lead to the formation of novel uORFs, uPeptides, or HLA uLigands and
explain their potential implication in tumor biology. Ultimately, we speculate on a potential use of uPeptides as peptide drugs and discuss how uPeptides and HLA uLigands may facilitate translational inhibition of oncogenic protein messages and immunotherapeutic approaches in cancer therapy
The prognostic potential of alkaline phosphatase and lactic acid dehydrogenase in bmCRPC patients without significant PSA response under enzalutamide
No full textBackground: In patients with bone metastatic castration-resistant prostate cancer (bmCRPC) on systemic treatment, it is difficult to differentiate between continuous rise of prostate specific antigen (PSA) representing progression, and PSA-surge, which is followed by clinical response or stable disease. The purpose of this study was to evaluate the prognostic value of dynamic changes of alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) levels as a predictor of clinical efficacy or therapeutic resistance of patients who do not show a sufficient initial PSA decline of ≥50% from baseline during early therapy with Enzalutamide. Methods: Forty-eight men with bmCRPC on Enzalutamide 07/2010-09/2019 with initially rising PSA were analyzed. We monitored PSA, LDH and ALP at week 0, 2, 4, and every 4 weeks thereafter and analyzed the correlation between ALP rising at 12 weeks with or without LDH-normalization and the association with survival. For this we used Kaplan Meier analysis and uni- and multivariate cox-regression models. Results: In Kaplan-Meier analysis, ALP rising at 12 weeks with or without LDH-normalization was associated with significantly worse median progression-free survival (PFS) of 3 months vs. 5 months (Log rank P = 0.02) and 3 months vs. 5 months (P = 0.01), respectively and overall survival (OS) with 8 months vs. 15 months (P = 0.02) and 8 months vs. 17 months (P < 0.01). In univariate analysis of PFS, ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization and application of Enzalutamide after chemotherapy showed a statistically significant association towards shorter PFS (hazard ratio (HR): 0.51, P = 0.04; HR: 0.48, P = 0.03; HR: 0.48, P = 0.03). Worse OS was significantly associated with ALP rising at 12 weeks alone, ALP rising at 12 weeks without LDH-normalization, and application of Enzalutamide after chemotherapy (HR: 0.47, P = 0.02; HR: 0.36, P < 0.01; HR: 0.31, P < 0.01). In multivariate analysis only the application of Enzalutamide after chemotherapy remained an independent prognostic factor for worse OS (HR: 0.36, P = 0.01). Conclusions: Dynamic changes of ALP (non-rise) and LDH (normalization) under therapy with Enzalutamide may be associated with clinical benefit, better PFS, and OS in patients with bmCRPC who do not show a PSA decline
Toll-like receptor 3 activation promotes joint degeneration in osteoarthritis
No full textOsteoarthritis (OA) is characterized by cartilage degradation that is induced by inflammation. Sterile inflammation can be caused by damage-associated molecular patterns that are released by chondrocytes and activate pattern recognition receptors. We evaluate the role of toll-like receptor-3-activating RNA in the pathogenesis of OA. Toll-like receptor 3 (TLR3) was detected by semiquantitative reverse transcriptase PCR, western blotting and microscopy. Rhodamine-labelled poly(I:C) was used to image uptake in chondrocytes and full-thickness cartilage. The production of IFNβ in chondrocytes after stimulation with poly(I:C) as well as in the synovial fluid of OA patients was measured using ELISA. Chondrocyte apoptosis was chemically induced using staurosporine. Immunohistochemistry was performed to examine TLR3 expression and apoptosis in human and murine OA cartilage. RNA in synovial fluid was quantified by RiboGreen assay. Destabilisation of the medial meniscus was performed in TLR3−/− and wildtype mice. OA was assessed after eight weeks using OARSI score. TLR3 expression was confirmed by western blot and RT-PCR. Poly(I:C) was internalised by chondrocytes as well as cartilage and caused an increase of IFNβ production in murine (11.46 ± 11.63 (wo) to 108.7 ± 25.53 pg/ml; N = 6) and human chondrocytes (1.88 ± 0.32 (wo) to 737.6 ± 130.5 pg/ml; N = 3; p < 0.001). OA cartilage showed significantly more TLR3-positive (KL0 = 0.22 ± 0.24; KL4 = 6.02 ± 6.75; N ≥ 15) and apoptotic chondrocytes (KL0 = 0.6 ± 1.02; KL4 = 9.78 ± 7.79; N ≥ 12) than healthy cartilage (p < 0.001). Staurosporine-induced chondrocyte apoptosis causes a dose-dependent RNA release (0 ng/ml = 1090 ± 39.1 ng/ml; 1000 ng/ml=2014 ± 160 ng/ml; N = 4; p < 0.001). Human OA synovial fluid contained increased concentrations of RNA (KL0-2 = 3408 ± 1129 ng/ml; KL4 = 4870 ± 1612ng/ml; N ≥ 7; p < 0.05) and IFNβ (KL0-2 = 41.95 ± 92.94 ng/ml; KL3 = 1181 ± 1865ng/ml; N ≥ 8; p < 0.05). TLR3−/− mice showed reduced cartilage degradation eight weeks after OA induction (OARSI WT = 5.5 ± 0.04; TLR3−/− = 3.75 ± 1.04; N ≥ 6) which was accompanied by gradually decreasing levels of TUNEL-positive cells (WT = 34.87 ± 24.10; TLR3−/ = 19.64 ± 7.89) resulting in decreased IFNβ expression (WT = 12.57 ± 5.43; TLR3−/− = 6.09 ± 2.07) in cartilage (p < 0.05). The release of RNA by apoptotic chondrocytes thus activating TLR3 signalling is one possible way of perpetuating inflammatory cartilage changes. The inhibition of TLR3 could be a possible therapeutic target for OA treatment
Trace element partitioning between pyrochlore, microlite, fersmite and silicate melts
No full textWe present experimentally determined trace element partition coefficients (D) between pyrochlore-group minerals (Ca2(Nb,Ta)2O6(O,F)), Ca fersmite (CaNb2O6), and silicate melts. Our data indicate that pyrochlores and fersmite are able to strongly fractionate trace elements during the evolution of SiO2-undersaturated magmas. Pyrochlore efficiently fractionates Zr and Hf from Nb and Ta, with DZr and DHf below or equal to unity, and DNb and DTa significantly above unity. We find that DTa pyrochlore-group mineral/silicate melt is always higher than DNb, which agrees with the HFSE partitioning of all other Ti–rich minerals such as perovskite, rutile, ilmenite or Fe-Ti spinel. Our experimental partition coefficients also show that, under oxidizing conditions, DTh is higher than corresponding DU and this implies that pyrochlore-group minerals may fractionate U and Th in silicate magmas. The rare earth element (REE) partition coefficients are around unity, only the light REE are compatible in pyrochlore-group minerals, which explains the high rare earth element concentrations in naturally occurring magmatic pyrochlores
Transatlanticism and Translation
No full textGayatri Chakravorty Spivak erkannte 2003 in ihrem Essay "Death of a Discipline", dass der Eurozentrismus ein grundlegendes und wesentliches Merkmal der Komparatistik sei. Der Begriff 'Transatlanticism' wirkt entsprechend altmodisch. Um der abnehmenden Relevanz übersetzter Literatur in den USA und der zunehmenden globalen Dominanz englischsprachiger Literatur (in Übersetzung) entgegenzuwirken, ist er jedoch nützlich. Die transatlantische Übersetzungsgeschichte zwischen Deutschland und den USA hilft, die begünstigenden Faktoren für die gegenseitige Rezeption zu ermitteln: Verlagshäuser, die sich der gemeinsamen literarischen Geschichte verschreiben, das Engagement exilierter Verleger und herausragender Einzelpersönlichkeiten, persönliche Aquisitionsreisen und zielgruppengerechte Übersetzungen. Eine Perspektive bietet die internationale Debatte um Amanda Gorman: Ästhetische und politische Forderungen an ihre Übersetzungen wurden in der breiten Öffentlichkeit diskutiert.In her essay "Death of a Discipline" (2003) Gayatri Chakravorty Spivak recognized that Eurocentrism was a fundamental and essential feature of comparative studies. The term 'transatlanticism', thus, seems outdated. However, it is useful in countering the declining relevance of translated literature in the US and the increasing global dominance of English-language literature (in translation). The transatlantic translation history between Germany and the US helps to identify the factors favoring mutual reception: Publishing houses committing to a shared literary history, the engagement of exiled publishers and outstanding individuals, personal acquisition travels, and providing translations adequate for their target groups. The international debate about Amanda Gorman offers a promising perspective: aesthetic and political demands on her translations were discussed by the general public
Translational balancing questioned: Unaltered glycosylation during disulfiram treatment in mannosyl-oligosaccharide alpha-1,2-mannnosidase-congenital disorders of glycosylation (MAN1B1-CDG)
No full textMAN1B1-CDG is a multisystem disorder caused by mutations in MAN1B1, encoding the endoplasmic reticulum mannosyl-oligosaccharide alpha-1,2-mannnosidase. A defect leads to dysfunction within the degradation of misfolded glycoproteins. We present two additional patients with MAN1B1-CDG and a resulting defect in endoplasmic reticulum-associated protein degradation. One patient (P2) is carrying the previously undescribed p.E663K mutation. A therapeutic trial in patient 1 (P1) using disulfiram with the rationale to generate an attenuation of translation and thus a balanced, restored ER glycoprotein synthesis failed. No improvement of the transferrin glycosylation profile was seen