On the Relation between the General Affective Meaning and the Basic Sublexical, Lexical, and Inter-lexical Features of Poetic Texts - A Case Study Using 57 Poems of H. M. Enzensberger

The literary genre of poetry is inherently related to the expression and elicitation of emotion via both content and form. To explore the nature of this affective impact at an extremely basic textual level, we collected ratings on eight different general affective meaning scales—valence, arousal, friendliness, sadness, spitefulness, poeticity, onomatopoeia, and liking—for 57 German poems (“die verteidigung der wölfe”) which the contemporary author H. M. Enzensberger had labeled as either “friendly,” “sad,” or “spiteful.” Following Jakobson's (1960) view on the vivid interplay of hierarchical text levels, we used multiple regression analyses to explore the specific influences of affective features from three different text levels (sublexical, lexical, and inter-lexical) on the perceived general affective meaning of the poems using three types of predictors: (1) Lexical predictor variables capturing the mean valence and arousal potential of words; (2) Inter-lexical predictors quantifying peaks, ranges, and dynamic changes within the lexical affective content; (3) Sublexical measures of basic affective tone according to sound-meaning correspondences at the sublexical level (see Aryani et al., 2016). We find the lexical predictors to account for a major amount of up to 50% of the variance in affective ratings. Moreover, inter-lexical and sublexical predictors account for a large portion of additional variance in the perceived general affective meaning. Together, the affective properties of all used textual features account for 43–70% of the variance in the affective ratings and still for 23–48% of the variance in the more abstract aesthetic ratings. In sum, our approach represents a novel method that successfully relates a prominent part of variance in perceived general affective meaning in this corpus of German poems to quantitative estimates of affective properties of textual components at the sublexical, lexical, and inter-lexical level

Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations

Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. This method can be used to estimate DILI risk if the maximal blood concentration (Cmax) of the test compound is known. Moreover, an ADI can be estimated even for compounds without information on blood concentrations. To systematically optimize the in vitro system, two novel test performance metrics were introduced, the toxicity separation index (TSI) which quantifies how well a test differentiates between hepatotoxic and non-hepatotoxic compounds, and the toxicity estimation index (TEI) which measures how well hepatotoxic blood concentrations in vivo can be estimated. In vitro test performance was optimized for a training set of 28 compounds, based on TSI and TEI, demonstrating that (1) concentrations where cytotoxicity first becomes evident in vitro (EC10) yielded better metrics than higher toxicity thresholds (EC50); (2) compound incubation for 48 h was better than 24 h, with no further improvement of TSI after 7 days incubation; (3) metrics were moderately improved by adding gene expression to the test battery; (4) evaluation of pharmacokinetic parameters demonstrated that total blood compound concentrations and the 95%-population-based percentile of Cmax were best suited to estimate human toxicity. With a support vector machine-based classifier, using EC10 and Cmax as variables, the cross-validated sensitivity, specificity and accuracy for hepatotoxicity prediction were 100, 88 and 93%, respectively. Concentrations in the culture medium allowed extrapolation to blood concentrations in vivo that are associated with a specific probability of hepatotoxicity and the corresponding oral doses were obtained by reverse modeling. Application of this in vitro/in silico method to the rat hepatotoxicant pulegone resulted in an ADI that was similar to values previously established based on animal experiments. In conclusion, the proposed method links oral doses and blood concentrations of test compounds to the probability of hepatotoxicity

The Affective Nature of Phonological Iconicity

Alternativtitel: Klang ist von Bedeutun

Dairy-Based Emulsions: Viscosity Affects Fat Difference Thresholds and Sweetness Perception

In complex emulsions, viscosity or viscosity-associated sensory attributes such as creaminess are important for quality assessment and product differentiation. Two sets of emulsions with fat or locust bean gum content being varied at seven levels were developed; the two emulsions at each level had similar apparent viscosity. Additionally, sugar concentration was kept constant either with respect to total emulsion, or with respect to the aqueous phase. Series of two-alternative forced choice tests were performed with one constant stimulus, and just noticeable differences were calculated using probability regression. The results show that, when viscosity was not compensated, it was easy for the subjects to (a) distinguish emulsions with different fat content when the fat content was addressed in the question, and to (b) distinguish emulsions with different fat or locust bean gum content when creaminess was addressed. For the latter descriptor, it is of minor importance whether viscosity is altered by fat content or a thickener. Weber fractions that were calculated for viscosity were approximately 0.20. The quantitative effects of viscosity on sweetness, however, depend on how product rheology was modified

ERPs reveal an iconic relation between sublexical phonology and affective meaning

Stimulus materials, data, and analysis script for this ERP experimen

Phonological Iconicity electrifies: An ERP study on affective sound-to-meaning correspondences in German

While linguistic theory posits an arbitrary relation between signifiers and the signified (de Saussure, 1916), our analysis of a large-scale German database containing affective ratings of words revealed that certain phoneme clusters occur more often in words denoting concepts with negative and arousing meaning. Here, we investigate how such phoneme clusters that potentially serve as sublexical markers of affect can influence language processing. We registered the EEG signal during a lexical decision task with a novel manipulation of the words’ putative sublexical affective potential: the means of valence and arousal values for single phoneme clusters, each computed as a function of respective values of words from the database these phoneme clusters occur in. Our experimental manipulations also investigate potential contributions of formal salience to the sublexical affective potential: Typically, negative high-arousing phonological segments—based on our calculations—tend to be less frequent and more structurally complex than neutral ones. We thus constructed two experimental sets, one involving this natural confound, while controlling for it in the other. A negative high-arousing sublexical affective potential in the strictly controlled stimulus set yielded an early posterior negativity (EPN), in similar ways as an independent manipulation of lexical affective content. When other potentially salient formal features at the sublexical level were not controlled for, the effect of the sublexical affective potential was strengthened and prolonged (250-650 ms), presumably because formal salience helps making specific phoneme clusters efficient sublexical markers of negative high-arousing affective meaning. These neurophysiological data support the assumption that the organization of a language´s vocabulary involves systematic sound-to-meaning correspondences at the phonemic level that influence the way we process language

Phonological Iconicity Electrifies:An ERP Study on Affective Sound-to-Meaning Correspondences in German

While linguistic theory posits an arbitrary relation between signifiers and the signified (de Saussure, 1916), our analysis of a large-scale German database containing affective ratings of words revealed that certain phoneme clusters occur more often in words denoting concepts with negative and arousing meaning. Here, we investigate how such phoneme clusters that potentially serve as sublexical markers of affect can influence language processing. We registered the EEG signal during a lexical decision task with a novel manipulation of the words' putative sublexical affective potential: the means of valence and arousal values for single phoneme clusters, each computed as a function of respective values of words from the database these phoneme clusters occur in. Our experimental manipulations also investigate potential contributions of formal salience to the sublexical affective potential: Typically, negative high-arousing phonological segments—based on our calculations—tend to be less frequent and more structurally complex than neutral ones. We thus constructed two experimental sets, one involving this natural confound, while controlling for it in the other. A negative high-arousing sublexical affective potential in the strictly controlled stimulus set yielded an early posterior negativity (EPN), in similar ways as an independent manipulation of lexical affective content did. When other potentially salient formal features at the sublexical level were not controlled for, the effect of the sublexical affective potential was strengthened and prolonged (250–650 ms), presumably because formal salience helps making specific phoneme clusters efficient sublexical markers of negative high-arousing affective meaning. These neurophysiological data support the assumption that the organization of a language's vocabulary involves systematic sound-to-meaning correspondences at the phonemic level that influence the way we process language

Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release

Abstract Myotonic dystrophy type 2 (DM2) is a tetranucleotide CCTG repeat expansion disease associated with an increased prevalence of autoimmunity. Here, we identified an elevated type I interferon (IFN) signature in peripheral blood mononuclear cells and primary fibroblasts of DM2 patients as a trigger of chronic immune stimulation. Although RNA-repeat accumulation was prevalent in the cytosol of DM2-patient fibroblasts, type-I IFN release did not depend on innate RNA immune sensors but rather the DNA sensor cGAS and the prevalence of mitochondrial DNA (mtDNA) in the cytoplasm. Sublethal mtDNA release was promoted by a chronic activation of the ATF6 branch of the unfolded protein response (UPR) in reaction to RNA-repeat accumulation and non-AUG translated tetrapeptide expansion proteins. ATF6-dependent mtDNA release and resulting cGAS/STING activation could also be recapitulated in human THP-1 monocytes exposed to chronic endoplasmic reticulum (ER) stress. Altogether, our study demonstrates a novel mechanism by which large repeat expansions cause chronic endoplasmic reticulum stress and associated mtDNA leakage. This mtDNA is, in turn, sensed by the cGAS/STING pathway and induces a type-I IFN response predisposing to autoimmunity. Elucidating this pathway reveals new potential therapeutic targets for autoimmune disorders associated with repeat expansion diseases

CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies

The neurofibromatoses (NF) are autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect more people worldwide than Duchenne muscular dystrophy and Huntington's disease combined. NF1 and NF2 are caused by mutations of known tumor suppressor genes (NF1 and NF2, respectively). For schwannomatosis, although mutations in SMARCB1 were identified in a subpopulation of schwannomatosis patients, additional causative gene mutations are still to be discovered. Individuals with NF1 may demonstrate manifestations in multiple organ systems, including tumors of the nervous system, learning disabilities, and physical disfigurement. NF2 ultimately can cause deafness, cranial nerve deficits, and additional severe morbidities caused by tumors of the nervous system. Unmanageable pain is a key finding in patients with schwannomatosis. Although today there is no marketed treatment for NF-related tumors, a significant number of clinical trials have become available. In addition, significant preclinical efforts have led to a more rational selection of potential drug candidates for NF trials. An important element in fueling this progress is the sharing of knowledge. For over 20 years the Children's Tumor Foundation has convened an annual NF Conference, bringing together NF professionals to share novel findings, ideas, and build collaborations. The 2012 NF Conference held in New Orleans hosted over 350 NF researchers and clinicians. This article provides a synthesis of the highlights presented at the conference and as such, is a "state-of-the-field" for NF research in 2012. © 2014 Wiley Periodicals, Inc.status: publishe