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  1. Free, publicly-accessible full text available May 19, 2024
  2. Cell–cell interactions are critical for transmitting signals among cells and maintaining their normal functions from the single-cell level to tissues. In cancer studies, interactions between drug-resistant and drug-sensitive cells play an important role in the development of chemotherapy resistance of tumors. As metabolites directly reflect the cell status, metabolomics studies provide insight into cell–cell communication. Mass spectrometry (MS) is a powerful tool for metabolomics studies, and single cell MS (SCMS) analysis can provide unique information for understanding interactions among heterogeneous cells. In the current study, we utilized a direct co-culture system (with cell–cell contact) to study metabolomics of single cells affected by cell–cell interactions in their living status. A fluorescence microscope was utilized to distinguish these two types of cells for SCMS metabolomics studies using the Single-probe SCMS technique under ambient conditions. Our results show that through interactions with drug-resistant cells, drug-sensitive cancer cells acquired significantly increased drug resistance and exhibited drastically altered metabolites. Further investigation found that the increased drug resistance was associated with multiple metabolism regulations in drug-sensitive cells through co-culture such as the upregulation of sphingomyelins lipids and lactic acid and the downregulation of TCA cycle intermediates. The method allows for direct MS metabolomics studies of individual cells labeled with fluorescent proteins or dyes among heterogeneous populations. 
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  3. Human efficiency in finding a target in an image has attracted the attention of machine learning researchers, but what about when no target is there? Knowing how people search in the absence of a target, and when they stop, is important for Human-computer-interaction systems attempting to predict human gaze behavior in the wild. Here we report a rigorous evaluation of target-absent search behavior using the COCO-Search18 dataset to train stateof- the-art models. We focus on two specific aims. First, we characterize the presence of a target guidance signal in target-absent search behavior by comparing it to targetpresent guidance and free viewing. We do this by comparing how well a model trained on one type of fixation behavior (target-present, target-absent, free viewing) can predict behavior in either the same or different task. To compare target-absent search to free viewing behavior we created COCO-FreeView, a dataset of free-viewing fixations for the same images used in COCO-Search18. These comparisons revealed the existence of a target guidance signal in targetabsent search, albeit one much less dominant compared to when a target actually appeared in an image, and that the target-absent guidance signal was similar to free viewing in that saliency and center bias were both weighted more than guidance from target features. Our second aim focused on the stopping criteria, a question intrinsic to target-absent search. Here we propose to train a foveated target detector whose target detection representation is sensitive to the relationship between distance from the fovea. Then combining the predicted target detection representation with other information such as fixation history and subject ID, our model outperforms the baselines in predicting when a person stops moving his attention during target-absent search. 
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