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This article analyses the German language in Denmark in its various contexts of language ecology. A crucial aspect of this approach is that German is not only considered, for example, as an intensely taught and learned foreign language in the education system or as the vivid language of the German minority in the south of Jutland, but that all those areas in which the German language plays a role in the Danish society are dealt with, thus including the enormous importance of German in Danish tourism and in business and economic life in general. In this way, a systemic overview over the language ecology of German in Denmark can be reconstructed. For a better understanding of today’s situation of German in Denmark, a brief historical outline of the centuries of intensive language contact between German and Danish is provided at the end of the article.

Straipsnyje nagrinėjami konceptualieji lyginamosios vokiečių ir lietuvių kalbos gramatikos klausimai. Apžvelgiami pagrindiniai gramatikografijos ir lyginamosios kalbotyros darbai, į kuriuos reikia atsižvelgti renkantis teorinį lyginamosios gramatikos pagrindą. Straipsnio pradžioje trumpai aptariamas terminų lyginamasis (vergleichend), istorinis-lyginamasis (historisch-vergleichend), tipologinis (typologisch), kontrastyvinis (kontrastiv) ir gretinamasis (konfrontativ) metodas vartojimas. Keliami klausimai, kaip rašant lyginamąją vokiečių ir lietuvių kalbos gramatiką būtų galima taikyti įvairius lyginamuosius ar tipologinius bei kontrastyvinius aspektus. Toliau straipsnyje pristatoma diskusija, skirta pastaraisiais metais pasirodžiusioms vokiečių kalbos gramatikoms, kuriose vokiečių kalba lyginama su kitomis kalbomis, atkreipiamas dėmesys į šių gramatikų privalumus ir trūkumus. Be to, aptariamos gramatikų naudotojų grupės, gramatikų naudojimo ypatumai. Svarstoma, kokiai naudotojų grupei turėtų būti skirta vokiečių ir lietuvių kalbos lyginamoji gramatika. Straipsnyje taip pat pateikiama trumpa vokiečių ir lietuvių kalbų lyginamųjų darbų apžvalga. Straipsnio pabaigoje pristatoma vokiečių ir lietuvių kalbos lyginamosios gramatikos koncepcija ir brėžiama tolesnių darbų perspektyva. ------ In diesem Beitrag werden erstmals Überlegungen zu einer Grammatik vorgelegt, die das Deutsche und das Litauische einerseits aus formaler und andererseits aus funktionaler Perspektive vergleichend gegenüberstellt. Unter Bezugnahme auf jüngere deskriptive Konzeptionen in der Grammatikographie wie auch auf bewährte kontrastive Ansätze wird diskutiert, wie sich in einer solchen Grammatik sowohl allgemein-vergleichende bzw. typologische als auch kontrastive Aspekte vereinbaren lassen. Es werden wichtige Ergebnisse der kritischen Auseinandersetzung mit mehreren bereits erschienenen kontrastiven Grammatiken Deutsch – Sprache X einbezogen, und es wird die Frage nach dem Benutzerkreis und die Problematik der Mehrfachadressierung einer Grammatik diskutiert. Daran schließt sich ein kurzer Überblick über bereits erschienene Beiträge zum deutsch-litauischen Sprachvergleich an, auf die das vorgestellte Vorhaben zurückgreifen kann. Schließlich wird die Konzeption einer Grammatik des Deutschen und des Litauischen im Vergleich mit ihren unterschiedlichen Teilkomponenten skizziert sowie ein Ausblick auf die nächsten Schritte zur Ausführung der Projektidee gegeben.

Based on a corpus of articles from two regional subscription newspapers representing the most widespread type of daily papers in Germany, this contribution analyses quotations in headlines of press articles and their relation to the corresponding sequences in the text body, thus focussing on the quotations’ intratextual reference quality. It turns out, that a considerable part of these “quotations” shows modifications of the formulations given in the text body. How the modifications are actually formed is modelled by a five-stage scale, and which functions they fulfil is illustrated by selected examples.

Based on a corpus of articles from two regional subscription newspapers representing the most widespread type of daily papers in Germany, this contribution analyses quotations in headlines of press articles and their relation to the corresponding sequences in the text body, thus focussing on the quotations’ intratextual reference quality. It turns out, that a considerable part of these “quotations” shows modifications of the formulations given in the text body. How the modifications are actually formed is modelled by a five-stage scale, and which functions they fulfil is illustrated by selected examples.

T cell engaging bispecific antibodies have shown clinical proof of concept for hematologic malignancies. Still, cytokine release syndrome, neurotoxicity, and on-target-off-tumor toxicity, especially in the solid tumor setting, represent major obstacles. Second generation TCEs have been described that decouple cytotoxicity from cytokine release by reducing the apparent binding affinity for CD3 and/or the TAA but the results of such engineering have generally led only to reduced maximum induction of cytokine release and often at the expense of maximum cytotoxicity. Using ROR1 as our model TAA and highly modular camelid nanobodies, we describe the engineering of a next generation decoupled TCE that incorporates a “cytokine window” defined as a dose range in which maximal killing is reached but cytokine release may be modulated from very low for safety to nearly that induced by first generation TCEs. This latter attribute supports pro-inflammatory anti-tumor activity including bystander killing and can potentially be used by clinicians to safely titrate patient dose to that which mediates maximum efficacy that is postulated as greater than that possible using standard second generation approaches. We used a combined method of optimizing TCE mediated synaptic distance and apparent affinity tuning of the TAA binding arms to generate a relatively long but persistent synapse that supports a wide cytokine window, potent killing and a reduced propensity towards immune exhaustion. Importantly, this next generation TCE induced significant tumor growth inhibition in vivo but unlike a first-generation non-decoupled benchmark TCE that induced lethal CRS, no signs of adverse events were observed.

The optimization of the affinity of monoclonal antibodies is crucial for the development of drug candidates, as it can impact the efficacy of the drug and, thus, the dose and dosing regimen, limit adverse effects, and reduce therapy costs. Here, we present the affinity maturation of an EGFR×PD-L1 Two-in-One antibody for EGFR binding utilizing site-directed mutagenesis and yeast surface display. The isolated antibody variants target EGFR with a 60-fold-improved affinity due to the replacement of a single amino acid in the CDR3 region of the light chain. The binding properties of the Two-in-One variants were confirmed using various methods, including BLI measurements, real-time antigen binding measurements on surfaces with a mixture of both recombinant proteins and cellular binding experiments using flow cytometry as well as real-time interaction cytometry. An AlphaFold-based model predicted that the amino acid exchange of tyrosine to glutamic acid enables the formation of a salt bridge to an arginine at EGFR position 165. This easily adaptable approach provides a strategy for the affinity maturation of bispecific antibodies with respect to the binding of one of the two antigens.

Although a considerable number of disease-related biomolecular interactions occur in the cytosol, therapeutic and diagnostic application of target-specific binding proteins is largely confined to surface-exposed or extracellular targets. Therefore, protein-cargo delivery approaches, including cell-penetrating peptides and cytosol-penetrating antibodies, are being explored to overcome this limitation. In this context, we have developed a modular approach for cytosolic penetration of tumor cells based on bispecific antibodies containing a masked cytosol-penetrating Fab on one arm and a tumor-targeting scFv linked via an endosomal cleavable linker on the other arm. The relevance of the antigen-specific binding, internalization, and cytosolic cargo delivery was demonstrated in several in vitro assays using different cell lines with anti-B7-H3 scFv, the well-characterized trastuzumab (HER2), and inotuzumab (CD22) as examples. In addition, presence of the masking moiety to prevent non-specific surface binding, as well as the activation of cytosol-penetrating capabilities in the tumor microenvironment upon release by tumor-specific proteases was confirmed using the catalytic domain of Pseudomonas exotoxin as model cargo for cytosol delivery. Tumor microenvironment-dependent as well as tumor-associated antigen-specific cytosol-penetrating antibodies of the type developed here have the potential to serve as a modular platform to deliver macromolecular cargoes for addressing intracellular targets in tumor cells.