Dummheit, Tollheit, Weisheit : Nikolaus Harscher und die konkurrierenden Narren-Diskurse um 1800

In der literarischen Fehde zwischen Frühromantik und Spätaufklärung kommt es um 1800 zu wechselseitigen Dummheitsvorwürfen, aber auch zur grundsätzlichen Aufwertung nicht-rationalen Denkens bzw. Sprechens als dichterische Inspiration oder Narrenrede. Der erste Teil des Aufsatzes exemplifiziert diese paradoxen Beziehungen an Tiecks Komödie Prinz Zerbino, Kotzebues Satire Der hyperboreeische Esel und den von Varnhagen mitverfassten Testimonia Auctorum de Merkelio. In einem zweiten Schritt wird anhand des Steffens- und Schleiermacher-Schülers Nikolaus Harscher die krisenhafte Zuspitzung des romantischen Subjektivismus vorgeführt: Der ironische Preis von Dummheit und Faulheit und die Zitate aus Shakespeare’schen Narrenreden in Harschers Briefen aus Halle 1807 können kaum die existenzielle Gefährdung verdecken, die später bei ihm zum Wahnsinn führt. Noch in den Goethe-Exzerpten aus Harschers letzter Zeit lässt sich, wie im Schlussteil ausgeführt, die Spur von Erasmus’ Moriae Encomium wiederfinden.In the literary feud between early Romanticism and late Enlightenment, around 1800 there were mutual accusations of stupidity, but also a fundamental revaluation of non-rational thinking or speaking as poetic inspiration or fool’s speech. The first part of the essay exemplifies these paradoxical relationships in Tieck’s comedy Prinz Zerbino, Kotzebue’s satire Der hyperboreeische Esel and Testimonia Auctorum de Merkelio, co-authored by Varnhagen. In a second step, the crisis-ridden aggravation of Romantic subjectivism is demonstrated on the basis of Steffens’s and Schleiermacher’s pupil Nikolaus Harscher: The ironic praise of stupidity and laziness and the quotations from Shakespeare’s fool’s speeches in Harscher’s letters from Halle 1807 can hardly conceal the existential threat that later leads him to madness. Even in Goethe’s excerpts from Harscher’s latest lifetime, as explained in the final part, the trace of Erasmus’s Moriae Encomium can be found.In der literarischen Fehde zwischen Frühromantik und Spätaufklärung kommt es um 1800 zu wechselseitigen Dummheitsvorwürfen, aber auch zur grundsätzlichen Aufwertung nicht-rationalen Denkens bzw. Sprechens als dichterische Inspiration oder Narrenrede. Der erste Teil des Aufsatzes exemplifiziert diese paradoxen Beziehungen an Tiecks Komödie Prinz Zerbino, Kotzebues Satire Der hyperboreeische Esel und den von Varnhagen mitverfassten Testimonia Auctorum de Merkelio. In einem zweiten Schritt wird anhand des Steffens- und Schleiermacher-Schülers Nikolaus Harscher die krisenhafte Zuspitzung des romantischen Subjektivismus vorgeführt: Der ironische Preis von Dummheit und Faulheit und die Zitate aus Shakespeare’schen Narrenreden in Harschers Briefen aus Halle 1807 können kaum die existenzielle Gefährdung verdecken, die später bei ihm zum Wahnsinn führt. Noch in den Goethe-Exzerpten aus Harschers letzter Zeit lässt sich, wie im Schlussteil ausgeführt, die Spur von Erasmus’ Moriae Encomium wiederfinden

Ein Brief aus Halle (1807) und die Überlieferung von Schleiermachers Charaden

Welchen Weg nahm die Textgeschichte von Schleiermachers Rätselgedichten zwischen der ersten eigenhändigen Niederschrift ca. 1806 und den ältesten – einer klaren Autorisation ermangelnden, in der Textgestalt stark differierenden – Drucken in den 1820er und 1830er Jahren? In dieser unklaren Sachlage hat die Schleiermacher-Philologie auch eine Abschrift von unbekannter Hand als Textzeugen (von zweifelhaftem Stellenwert) diskutiert, die sich aufgrund des zugehörigen Briefs und eines Handschriftenvergleichs jetzt eindeutig zuordnen und datieren lässt. Sie dokumentiert die Zirkulation der geselligen Gelegenheitsgedichte im Hallenser Kreis 1806/07 und bildet zugleich die Quelle für den zweiten nachweisbaren Druck 1837. Dies sei im Folgenden ausführlich dargelegt und begründet.What path did the textual history of Schleiermacher’s Charades take between the first handwritten transcription around 1806 and the oldest printings in the 1820s and 1830s – which lack a clear authorisation and differ greatly in textual form? In this unclear situation, Schleiermacher philology has also discussed a copy by an unknown hand as a textual witness (of dubious value), which can now be clearly assigned and dated on the basis of the accompanying letter and a comparison of manuscripts. It documents the circulation of the sociable occasional poems in the Hallenser Kreis (Halle Circle) in 1806/07 and at the same time forms the source for the second verifiable print in 1837

GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice

The GluA2 subunit in heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels restricts Ca2+ permeability and block by polyamines, rendering linear the current-voltage relationship of these glutamate-gated cation channels. Although GluA2-lacking synaptic AMPA receptors occur in GABA-ergic inhibitory neurons, hippocampal CA1 pyramidal cell synapses are widely held to feature only GluA2 containing AMPA receptors. A controversy has arisen from reports of GluA2-lacking AMPA receptors at hippocampal CA3-to-CA1 cell synapses and a study contesting these findings. Here we sought independent evidence for the presence of GluA2-lacking AMPA receptors in CA1 pyramidal cell synapses by probing the sensitivity of their gated cation channels in wild-type (WT) mice and gene-targeted mouse mutants to philanthotoxin, a specific blocker of GluA2-lacking AMPA receptors. The mutants either lacked GluA2 for maximal philanthotoxin sensitivity, or, for minimal sensitivity, expressed GluA1 solely in a Q/R site-edited version or not at all. Our comparative electrophysiological analyses provide incontrovertible evidence for the presence in wild-type CA1 pyramidal cell synapses of GluA2-less AMPA receptor channels. This article is part of a Special Issue entitled “Calcium permeable AMPARs in synaptic plasticity and disease.

Phenotyping Young GluA1 Deficient Mice – A Behavioral Characterization in a Genetic Loss-of-Function Model

Alterations of glutamatergic neurotransmission have been implicated in neurodevelopmental and neuropsychiatric disorders. Mice lacking the GluA1 AMPA receptor subunit, encoded by the Gria1 gene, display multiple phenotypical features associated with glutamatergic dysfunction. While the phenotype of adult GluA1 deficient (Gria1-/- ) mice has been studied comprehensively, there are relevant gaps in knowledge about the course and the onset of behavioral alterations in the Gria1 knockout mouse model during post-weaning development. Based on former investigations in young wild-type mice, we exposed female and male adolescent Gria1-/- mice to a behavioral home-cage based testing battery designed for the purpose of severity assessment. Data obtained from mice with a constitutive loss of GluA1 were compared with those from wild-type littermates. We identified several genotype-dependent behavioral alterations in young Gria1-/- mice. While the preference for sweetness was not affected by genotype during adolescence, Gria1-/- mice displayed limited burrowing performance, and reached lower nest complexity scores. Analysis of home-cage based voluntary wheel running performance failed to confirm genotype-dependent differences. In contrast, when exposed to the open field test, Gria1-/- mice showed pronounced hyperlocomotion in early and late adolescence, and female Gria1 -/- mice exhibited thigmotaxis when prepubescent. We found increased corticosterone metabolite levels in fecal samples of adolescent Gria1-/- mice with females exhibiting increased adrenocortical activity already in prepubescence. Considering the course of behavioral modifications in early and late adolescence, the results do not support a persistent level of distress associated with GluA1 deficiency in the line. In contrast, the laboratory-specific readouts indicate transient, mild impairments of behavioral patterns relevant to animal welfare, and suggest a mild overall burden of the line

Polytraumaversorgung als Bereich der hochspezialisierten Medizin

Schwerverletzte Patientinnen und Patienten werden in der Schweiz im Rahmen der interkantonalen Vereinbarung der hochspezialisierten Medizin (IVHSM) behandelt. Das Swiss Trauma Board und die dort vereinten zwölf Schweizer Traumazentren arbeiten unter anderem mit dem deutschen Traumaregister zusammen, um eine bestmögliche Behandlung der Verletzten zu gewährleisten

Widely tunable 23 μm III-V-on-silicon Vernier lasers for broadband spectroscopic sensing

Heterogeneously integrating III-V materials on silicon photonic integrated circuits has emerged as a promising approach to make advanced laser sources for optical communication and sensing applications. Tunable semiconductor lasers operating in the 2-2.5 mu m range are of great interest for industrial and medical applications since many gases (e.g., CO2, CO, CH4) and biomolecules (such as blood glucose) have strong absorption features in this wavelength region. The development of integrated tunable laser sources in this wavelength range enables low-cost and miniature spectroscopic sensors. Here we report heterogeneously integrated widely tunable III-V-on-silicon Vernier lasers using two silicon microring resonators as the wavelength tuning components. The laser has a wavelength tuning range of more than 40 nm near 2.35 mu m. By combining two lasers with different distributed Bragg reflectors, a tuning range of more than 70 nm is achieved. Over the whole tuning range, the side-mode suppression ratio is higher than 35 dB. As a proof-of-principle, this III-V-on-silicon Vernier laser is used to measure the absorption lines of CO. The measurement results match very well with the high-resolution transmission molecular absorption (HITRAN) database and indicate that this laser is suitable for broadband spectroscopy. (C) 2018 Chinese Laser Pres

Deep learning-based denoising streamed from mobile phones improves speech-in-noise understanding for hearing aid users

The hearing loss of almost half a billion people is commonly treated with hearing aids. However, current hearing aids often do not work well in real-world noisy environments. We present a deep learning based denoising system that runs in real time on iPhone 7 and Samsung Galaxy S10 (25ms algorithmic latency). The denoised audio is streamed to the hearing aid, resulting in a total delay of around 75ms. In tests with hearing aid users having moderate to severe hearing loss, our denoising system improves audio across three tests: 1) listening for subjective audio ratings, 2) listening for objective speech intelligibility, and 3) live conversations in a noisy environment for subjective ratings. Subjective ratings increase by more than 40%, for both the listening test and the live conversation compared to a fitted hearing aid as a baseline. Speech reception thresholds, measuring speech understanding in noise, improve by 1.6 dB SRT. Ours is the first denoising system that is implemented on a mobile device, streamed directly to users' hearing aids using only a single channel as audio input while improving user satisfaction on all tested aspects, including speech intelligibility. This includes overall preference of the denoised and streamed signal over the hearing aid, thereby accepting the higher latency for the significant improvement in speech understanding

Inherited and de novo SHANK2 variants associated with autism spectrum disorder impair neuronal morphogenesis and physiology

Mutations in the postsynaptic scaffolding gene SHANK2 have recently been identified in individuals with autism spectrum disorder (ASD) and intellectual disability. However, the cellular and physiological consequences of these mutations in neurons remain unknown. We have analyzed the functional impact caused by two inherited and one de novo SHANK2 mutations from ASD individuals (L1008_P1009dup, T1127M, R462X). Although all three variants affect spine volume and have smaller SHANK2 cluster sizes, T1127M additionally fails to rescue spine volume in Shank2 knock-down neurons. R462X is not able to rescue spine volume and dendritic branching and lacks postsynaptic clustering, indicating the most severe dysfunction. To demonstrate that R462X when expressed in mouse can be linked to physiological effects, we analyzed synaptic transmission and behavior. Principal neurons of mice expressing rAAV-transduced SHANK2-R462X present a specific, long-lasting reduction in miniature postsynaptic AMPA receptor currents. This dominant negative effect translates into dose-dependent altered cognitive behavior of SHANK2-R462X-expressing mice, with an impact on the penetrance of ASD

Silencing and Un-silencing of Tetracycline-Controlled Genes in Neurons

To identify the underlying reason for the controversial performance of tetracycline (Tet)-controlled regulated gene expression in mammalian neurons, we investigated each of the three components that comprise the Tet inducible systems, namely tetracyclines as inducers, tetracycline-transactivator (tTA) and reverse tTA (rtTA), and tTA-responsive promoters (Ptets). We have discovered that stably integrated Ptet becomes functionally silenced in the majority of neurons when it is inactive during development. Ptet silencing can be avoided when it is either not integrated in the genome or stably-integrated with basal activity. Moreover, long-term, high transactivator levels in neurons can often overcome integration-induced Ptet gene silencing, possibly by inducing promoter accessibility

Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice:relevance to neuropsychiatric disorders

Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity, including the Gria1 gene which codes for the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Gria1−/− mice exhibit a phenotype relevant for neuropsychiatric disorders, including reduced synaptic plasticity and, at the behavioural level, attentional deficits leading to aberrant salience. In this study we report a striking reduction of EEG power density including the spindle-frequency range (10–15 Hz) during sleep in Gria1−/− mice. The reduction of spindle-activity in Gria1−/− mice was accompanied by longer REM sleep episodes, increased EEG slow-wave activity in the occipital derivation during baseline sleep, and a reduced rate of decline of EEG slow wave activity (0.5–4 Hz) during NREM sleep after sleep deprivation. These data provide a novel link between glutamatergic dysfunction and sleep abnormalities in a schizophrenia-relevant mouse model