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ELIZABETH A. ROY MARK HOLLINS 《Somatosensory & motor research》2013,30(2):134-145
Subjective impressions of pitch for 80 different sinusoidal vibrotactile stimuli delivered to the index finger were measured by free magnitude estimation in four subjects. In three of the subjects, pitch at a given frequency decreased as stimulus amplitude increased. The data of these subjects were well described by a model of pitch based on the relative levels of activation of the three major tactile channels. The main element in this model was a ratio of P channel activity to the sum of the activity levels of the P, NPI, and NPIII channels. Activity levels of the channels were estimated on the basis of the psychophysical literature, including a study of vibrotactile loudness using the same subjects and stimuli as those employed here. A fourth subject, whose pattern of loudness judgments had previously been shown to differ from those of the other subjects, did not conform to this pitch model: her data revealed significant increases in pitch with increases in amplitude, and appear to reflect an inability to combine signals across vibrotactile channels. Pitch changes resulting from vibrotactile adaptation were directionally consistent with our ratio model: pitch was slightly increased by adaptation to a 25 Hz stimulus, and slightly decreased by 200 Hz adaptation. 相似文献
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ROSS A. MARKLEIN MATTHEW W. KLINKER KATHERINE A. DRAKE HANNAH G. POLIKOWSKY ELIZABETH C. LESSEY-MORILLON STEVEN R. BAUER 《Cytotherapy》2019,21(1):17-31
Background
Although a preponderance of pre-clinical data demonstrates the immunosuppressive potential of mesenchymal stromal cells (MSCs), significant heterogeneity and lack of critical quality attributes (CQAs) based on immunosuppressive capacity likely have contributed to inconsistent clinical outcomes. This heterogeneity exists not only between MSC lots derived from different donors, tissues and manufacturing conditions, but also within a given MSC lot in the form of functional subpopulations. We therefore explored the potential of functionally relevant morphological profiling (FRMP) to identify morphological subpopulations predictive of the immunosuppressive capacity of MSCs derived from multiple donors, manufacturers and passages.Methods
We profiled the single-cell morphological response of MSCs from different donors and passages to the functionally relevant inflammatory cytokine interferon (IFN)-γ. We used the machine learning approach visual stochastic neighbor embedding (viSNE) to identify distinct morphological subpopulations that could predict suppression of activated CD4+ and CD8+ T cells in a multiplexed quantitative assay.Results
Multiple IFN-γ–stimulated subpopulations significantly correlated with the ability of MSCs to inhibit CD4+ and CD8+ T-cell activation and served as effective CQAs to predict the immunosuppressive capacity of additional manufactured MSC lots. We further characterized the emergence of morphological heterogeneity following IFN-γ stimulation, which provides a strategy for identifying functional subpopulations for future single-cell characterization and enrichment techniques.Discussion
This work provides a generalizable analytical platform for assessing functional heterogeneity based on single-cell morphological responses that could be used to identify novel CQAs and inform cell manufacturing decisions. 相似文献47.
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