To adequately and permanently restore organ function after grafting, human tissue-engineered skin substitutes (TESs) must ultimately contain and preserve functional epithelial stem cells (SCs). It is therefore essential that a maximum of SCs be preserved during each in vitro step leading to the production of TESs such as the culture process and the elaboration of a skin cell bank by cryopreservation. To investigate the presence and functionality of epithelial SCs within the human TESs made by the self-assembly approach, slow-cycling cells were identified using 5'-bromo-2'-deoxyuridine (BrdU) in the three-dimensional construct. A subset of basal epithelial cells retained the BrdU label and was positive for the SC-associated marker keratin 19 within TESs after a chase of 21 days in culture post-BrdU labeling. Moreover, keratinocytes harvested from TESs gave rise to SC-like colonies in secondary monolayer subcultures, indicating that SCs were preserved within TESs. To evaluate the effect of cryopreservation with dimethyl sulfoxide and storage in liquid nitrogen on SCs, human epithelial cells were extracted from skin samples, amplified in culture, and used to produce TESs, before cryopreservation as well as after thawing. We found that the proportion and the growth potential of epithelial SCs in monolayer culture and in TESs remained constant before and after cryopreservation. Further, the functionality of these substitutes was demonstrated by successfully grafting human TESs on athymic mice for 6 months. We conclude that human epithelial skin SCs are adequately preserved upon human tissue reconstruction. Thus, these TESs produced by the self-assembly approach are suitable for clinical applications.
Society. His research interests cover computational, psychological and neuroscientific aspects of music cognition, with a particular focus on dynamic, predictive processing of melodic, rhythmic and harmonic structure, and its impact on emotional and aesthetic experience. He is the author of the IDyOM model of auditory expectation based on statistical learning and probabilistic prediction. EXPECTANCY AND MUSICAL EMOTION3 Abstract Pitch and timing information work hand in hand to create a coherent piece of music; but what happens when this information goes against the norm? Relationships between musical expectancy and emotional responses were investigated in a study conducted with 40 participants: 20 musicians and 20 non-musicians. Participants took part in one of two behavioural paradigms measuring continuous expectancy or emotional responses (arousal and valence) while listening to folk melodies that exhibited either high or low pitch predictability and high or low onset predictability. The causal influence of pitch predictability was investigated in an additional condition where pitch was artificially manipulated and a comparison conducted between original and manipulated forms; the dynamic correlative influence of pitch and timing information and its perception on emotional change during listening was evaluated using cross-sectional time series analysis. The results indicate that pitch and onset predictability are consistent predictors of perceived expectancy and emotional response, with onset carrying more weight than pitch. In addition, musicians and non-musicians do not differ in their responses, possibly due to shared cultural background and knowledge. The results demonstrate in a controlled lab-based setting a precise, quantitative relationship between the predictability of musical structure, expectation and emotional response.
What makes a piece of music appear complex to a listener? This research extends previous work by Eerola (2016), examining information content generated by a computational model of auditory expectation (IDyOM) based on statistical learning and probabilistic prediction as an empirical definition of perceived musical complexity. We systematically manipulated the melody, rhythm, and harmony of short polyphonic musical excerpts using the model to ensure that these manipulations systematically varied information content in the intended direction. Complexity ratings collected from 28 participants were found to positively correlate most strongly with melodic and harmonic information content, which corresponded to descriptive musical features such as the proportion of out-of-key notes and tonal ambiguity. When individual differences were considered, these explained more variance than the manipulated predictors. Musical background was not a significant predictor of complexity ratings. The results support information content, as implemented by IDyOM, as an information-theoretic measure of complexity as well as extending IDyOM's range of applications to perceived complexity.
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