This volume discusses the characteristics and dynamics of urban language use, considering aspects such as contact, variation and change, as well as identity, indexicality, attitudes, and spatial ...factors including mobility, (counter-)urbanisation and diffusion processes. It presents modern methodological and conceptual ideas as well as new findings.
The city as a social structure has a distinct relationship with its inhabitants. It creates a socio-pragmatic environment that produces communicative characteristics in the form of usage patterns ...that go hand in hand with conventionalised practices (cf. Gal 1987) and are dependent on everyday-life contextual aspects.
Accordingly, research of urban varieties is ideally based on language data that is as authentic as possible and includes socio-demographic and diatopic aspects. Following this idea, the study presented examines the subjunctive II in urban Austria by analysing free conversations in formal and informal contexts (interviews and conversations among friends), and correlating the results with spatial and social parameters. The data used was collected in Vienna and Graz, the two largest cities in Austria, as well as in their respective surrounding areas and was grouped by gender, age and place of residence.
The subjunctive II is realised in synthetic as well as periphrastic forms (cf. Merkle 1993: 69–73.; Donhauser 1992; Glauninger 2008). In rural Austria speakers use the entire range of variants (cf. Ziegler/Glantschnig 2013; Breuer/Wittibschlager 2020), while urban speakers exhibit a much narrower range, as we show in our analysis. Striking features in the use of variants can be seen above all in the form of contrasting modes of construction, i. e. synthetic vs. periphrastic realisation. The study reveals that there are hardly any differences between the two urban centres and only minor differences between a city and its surrounding area. However, the inclusion of social parameters provides a more differentiated picture: Here, higher relative frequencies of synthetic forms are found among male and older speakers compared to female and younger speakers. Thus, a preference for more conservative forms among the former contrasts with a preference for more modern (analytical) variants among the latter.
These days, it is commonly forgotten that Bavarian-Austrian dialect art flourished in elite culture and even more in popular counterculture before 1800. The book makes the amazing variety of forms ...and modes of operation visible again. In eight chapters, the most important, predominantly unedited texts and their authors are presented, contextualized, and related to current research fields using an interdisciplinary approach.
Schon vor 1800 war Literatur in und mit Dialekt ein wesentlicher, prägender Bestandteil der Elite-, Alltags- und Komplementärkultur im bairisch-österreichischen Sprachraum. Das Buch präsentiert erstmals die wichtigsten Ausdrucksformen, Arbeiten und Autoren, kontextualisiert die bislang überwiegend nicht edierten Werke aus einer Vielzahl an Archiven und Bibliotheken und stellt sie in aktuelle kulturwissenschaftliche Forschungszusammenhänge.
Abstract
Aim
Long QT syndrome (LQTS) is a cardiac channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Since current therapies often fail to prevent arrhythmic events in ...certain LQTS subtypes, new therapeutic strategies are needed. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, which enhances the repolarizing IKs current.
Methods and results
We investigated the effects of DHA in wild type (WT) and transgenic long QT Type 1 (LQT1; loss of IKs), LQT2 (loss of IKr), LQT5 (reduction of IKs), and LQT2–5 (loss of IKr and reduction of IKs) rabbits. In vivo ECGs were recorded at baseline and after 10 µM/kg DHA to assess changes in heart-rate corrected QT (QTc) and short-term variability of QT (STVQT). Ex vivo monophasic action potentials were recorded in Langendorff-perfused rabbit hearts, and action potential duration (APD75) and triangulation were assessed. Docosahexaenoic acid significantly shortened QTc in vivo only in WT and LQT2 rabbits, in which both α- and β-subunits of IKs-conducting channels are functionally intact. In LQT2, this led to a normalization of QTc and of its short-term variability. Docosahexaenoic acid had no effect on QTc in LQT1, LQT5, and LQT2–5. Similarly, ex vivo, DHA shortened APD75 in WT and normalized it in LQT2, and additionally decreased AP triangulation in LQT2.
Conclusions
Docosahexaenoic acid exerts a genotype-specific beneficial shortening/normalizing effect on QTc and APD75 and reduces pro-arrhythmia markers STVQT and AP triangulation through activation of IKs in LQT2 rabbits but has no effects if either α- or β-subunits to IKs are functionally impaired. Docosahexaenoic acid could represent a new genotype-specific therapy in LQT2.
Optimization approaches are important to design sustainable structures. In structural mechanics, different design objectives can be defined, for example, to minimize the required construction ...material or to maximize the structural durability. In this paper, the durability of a reinforced concrete (RC) structure is assessed by advanced finite element (FE) models to simulate the cracking behavior and the chloride transport process. The corrosion initiation time is used as durability measure to be maximized within an optimization approach, where the concrete cover is defined as design variable. The variability of structural loads and material parameters and unavoidable construction imprecision leads to a probabilistic reliability and durability assessment, where aleatory as well as epistemic uncertainties are quantified by random variables, intervals and probability‐boxes. The FE simulation models cannot directly be applied to structural analyses and optimizations with polymorphic uncertain parameters and design variables because of the high computational demand of the multi‐loop algorithm (Monte Carlo simulation, interval analysis, global optimization). In this paper, a new surrogate modeling strategy is presented, where artificial neural networks are trained sequentially to speed‐up the coupled mechanical and transport simulation FE models. The new approach is applied to the uncertainty quantification and the structural durability optimization of a RC structure.
Zusammenfassung
Die in Deutschland nichtregulierte Substanz Kratom mit dem psychoaktiven Wirkstoff Mitragynin wird hierzulande z. B. als Nahrungsergänzungsmittel vertrieben und führt in verschiedenen ...Dosierungen von stimulierenden bis zu sedierenden Effekten. Das Nebenwirkungsprofil reicht von Schwindel über Krampfanfälle bis zur Atemdepression. International sind bereits mehrere Todesfälle im Zusammenhang mit Kratom (Misch- und Monointoxikationen) berichtet worden. Es wird die erste tödliche Mitragyninmonointoxikation aus Deutschland vorgestellt.
Literatur in und mit Dialekt war auch vor 1800 ein wesentlicher, prägender Bestandteil der Elite-, Alltags- und Komplementärkultur im bairisch-österreichischen Sprachraum. Christian Neuhuber, ...Stefanie Edler, Elisabeth Zehetner präsentieren erstmals die wichtigsten Ausdrucksformen, Arbeiten und Autoren, kontextualisieren die bislang überwiegend nicht edierten Werke aus einer Vielzahl an Archiven und Bibliotheken und stellen sie in aktuelle kulturwissenschaftliche Forschungszusammenhänge.Literatur in und mit Dialekt war auch vor 1800 ein wesentlicher, prägender Bestandteil der Elite-, Alltags- und Komplementärkultur im bairisch-österreichischen Sprachraum. Christian Neuhuber, Stefanie Edler, Elisabeth Zehetner präsentieren erstmals die wichtigsten Ausdrucksformen, Arbeiten und Autoren, kontextualisieren die bislang überwiegend nicht edierten Werke aus einer Vielzahl an Archiven und Bibliotheken und stellen sie in aktuelle kulturwissenschaftliche Forschungszusammenhänge.
The jumonji C (JmjC) domain containing gene 6 (Jmjd6, previously known as phosphatidylserine receptor) has misleadingly been annotated to encode a transmembrane receptor for the engulfment of ...apoptotic cells. Given the importance of JmjC domain containing proteins in controlling a wide range of diverse biological functions, we undertook a comparative genomic analysis to gain further insights in Jmjd6 gene organisation, evolution, and protein function.
We describe here a semiautomated computational pipeline to identify and annotate JmjC domain containing proteins. Using a sequence segment N-terminal of the Jmjd6 JmjC domain as query for a reciprocal BLAST search, we identified homologous sequences in 62 species across all major phyla. Retrieved Jmjd6 sequences were used to phylogenetically analyse corresponding loci and their genomic neighbourhood. This analysis let to the identification and characterisation of a bi-directional transcriptional unit compromising the Jmjd6 and 1110005A03Rik genes and to the recognition of a new, before overseen Jmjd6 exon in mammals. Using expression studies, two novel Jmjd6 splice variants were identified and validated in vivo. Analysis of the Jmjd6 neighbouring gene 1110005A03Rik revealed an incident deletion of this gene in two out of three earlier reported Jmjd6 knockout mice, which might affect previously described conflicting phenotypes. To determine potentially important residues for Jmjd6 function a structural model of the Jmjd6 protein was calculated based on sequence conservation. This approach identified a conserved double-stranded beta-helix (DSBH) fold and a HxDxnH facial triad as structural motifs. Moreover, our systematic annotation in nine species identified 313 DSBH fold-containing proteins that split into 25 highly conserved subgroups.
We give further evidence that Jmjd6 most likely has a function as a nonheme-Fe(II)-2-oxoglutarate-dependent dioxygenase as previously suggested. Further, we provide novel insights into the evolution of Jmjd6 and other related members of the superfamily of JmjC domain containing proteins. Finally, we discuss possibilities of the involvement of Jmjd6 and 1110005A03Rik in an antagonistic biochemical pathway.
Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the ...spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration. Exclusive CD95L deletion in myeloid cells greatly decreased the number of neutrophils and macrophages infiltrating the injured spinal cord or the inflamed peritoneum after thioglycollate injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural cells, led to functional recovery of spinal injured animals. Our results indicate that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus, neutralization of CD95L should be considered as a means to create a controlled beneficial inflammatory response.
► Inflammation induces expression of CD95 ligand in myeloid cells ► Activating CD95 on myeloid cells induces their recruitment to the inflammatory site ► CD95 activates the SFK-Syk-PI3K pathway on myeloid cells ► Neutralization of CD95 ligand tames the innate inflammatory response
Herbs have successfully been used in traditional Chinese medicine for centuries. However, their curative mechanisms remain largely unknown. In this study, we show that Wogonin, derived from the ...traditional Chinese medicine Huang-Qin (Scutellaria baicalensis Georgi), induces apoptosis in malignant T cells in vitro and suppresses growth of human T-cell leukemia xenografts in vivo. Importantly, Wogonin shows almost no toxicity on T lymphocytes from healthy donors. Wogonin induces prolonged activation of PLCgamma1 via H(2)O(2) signaling in malignant T cells, which leads to sustained elevation of cytosolic Ca(2+) in malignant but not normal T cells. Subsequently, a Ca(2+) overload leads to disruption of the mitochondrial membrane. The selective effect of Wogonin is due to its differential regulation of the redox status of malignant versus normal T cells. In addition, we show that the L-type voltage-dependent Ca(2+) channels are involved in the intracellular Ca(2+) mobilization in T cells. Furthermore, we show that malignant T cells possess elevated amounts of voltage-dependent Ca(2+) channels compared with normal T cells, which further enhance the cytotoxicity of Wogonin for malignant T cells. Taken together, our data show a therapeutic potential of Wogonin for the treatment of hematologic malignancies.
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