Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in whole blood is critical to unravelling the complex and dynamic properties of these potential clinical markers. This task is challenging because these cells are present at parts per billion levels among normal blood cells. Here we report a new nanoparticle-enabled method for CTC characterization, called magnetic ranking cytometry, which profiles CTCs on the basis of their surface expression phenotype. We achieve this using a microfluidic chip that successfully processes whole blood samples. The approach classifies CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers, which is read out using magnetic nanoparticles. We deploy this new technique to reveal the dynamic phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth and aggressiveness. We also test magnetic ranking cytometry using blood samples collected from cancer patients.
AbstractThe classic view of narrative since the time of Aristotle is that plot structure is prioritized over characters in defining the nature of stories. According to this view, plot is an abstract structure external to the protagonist, and the protagonist’s actions are determined by the thematic goals of the plot. The current analysis calls for a reversal in the prioritization of these elements in creating a story. We present an Embodied Plot model in which character not only drives plot, but embodies plot as well. According to this model, the dramatic arc of plots is attributable to psychological processes occurring in the protagonist’s mind. Plot structure is thus isomorphic with the psychological and problem-solving experience of the protagonist inside the storyworld. We apply this model to a number of fairy tales to demonstrate how the dramatic arc of these stories can be explained in each case by the protagonist’s experientiality.
Plots have been described as having shapes based on the changes in tension that occur across a story. We present here a model of plot shape that is predicated on the alternating rises and falls in the protagonist’s emotional state. The basic tenet of the model is that, once the emotional valence of the beginning and ending of a story has been specified, then the internal phases of the story are constrained to connect these endpoints by oscillating between emotional rises and falls in a wavelike manner. This makes plot structure akin to a musical resonator – such as a flute – which can only conduct sound waves of certain discrete shapes depending on the structure of the tube’s endpoints. Using this metaphor, we describe four fundamental plot-shapes based on a 2 x 2 crossing of the emotional valence of a story’s beginning (happy beginning vs. sad beginning) and ending (happy ending vs. sad ending).
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