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The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level) and prime-target expressions (word level). Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences), target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time-and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.
Here we describe a novel conditional mouse lung tumor model for investigation of the pathogenesis of human lung cancer. On the basis of the frequent involvement of the Ras-RAF-MEK-ERK signaling pathway in human non-small cell lung carcinoma (NSCLC), we have explored the target cell availability, reversibility, and cell type specificity of transformation by oncogenic C-RAF. Targeting expression to alveolar type II cells or to Clara cells, the two likely precursors of human NSCLC, revealed differential tumorigenicity between these cells. Whereas expression of oncogenic C-RAF in alveolar type II cells readily induced multifocal macroscopic lung tumors independent of the developmental state, few tumors with type II pneumocytes features and incomplete penetrance were found when targeted to Clara cells. Induced tumors did not progress and were strictly dependent on the initiating oncogene. Deinduction of mice resulted in tumor regression due to autophagy rather than apoptosis. Induction of autophagic cell death in regressing lung tumors suggests the use of autophagy enhancers as a treatment choice for patients with NSCLC.
In an experimental analog of verbal examinations, the call-up situation, the effects of two dosages of a tranquillizing agent (lopirazepam) are compared to placebo treatment. 72 male and female, healthy, young volunteers have been randomly assigned to 12 groups of 6 subjects each. Pulse frequency and performance were registered. The results indicated differential drug effects which were interpreted according to the hypotheses of "differential effects of social stressors". If a situation was highly challenging for a subject, the application of a tranquillizer in an adequately high dosage enabled him to perform well in spite of or because of strong increases in pulse frequency.