PSMD14, a subunit of the 19S regulatory particles of the 26S proteasome, was recently identified as a potential prognostic marker and therapeutic target in diverse human cancers. Here, we show that the silencing and pharmacological blockade of PSMD14 in MDA-MB 435S breast cancer cells induce paraptosis, a non-apoptotic cell death mode characterized by extensive vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. The PSMD14 inhibitor, capzimin (CZM), inhibits proteasome activity but differs from the 20S proteasome subunit-inhibiting bortezomib (Bz) in that it does not induce aggresome formation or Nrf1 upregulation, which underlie Bz resistance in cancer cells. In addition to proteasome inhibition, the release of Ca2+ from the ER into the cytosol critically contributes to CZM-induced paraptosis. Induction of paraptosis by targeting PSMD14 may provide an attractive therapeutic strategy against cancer cells resistant to proteasome inhibitors or pro-apoptotic drugs.
As the Internet of Things (IoT) has become widespread, the demand for storing and querying data generated by things (e.g., moving sensors) is growing to obtain more useful information. One of the emerging queries on such IoT data is the spatio-temporal join, which joins data generated by different things but generated at (almost) the same time and location. In this paper, we propose an efficient method for processing spatio-temporal joins on IoT data. The proposed method divides the 3D spatio-temporal space into small, equal-sized spaces, called cells. As data is generated by things, the proposed method maintains the information about which thing's data are in which cells. When a spatio-temporal join between specified things is requested, the proposed method first identifies cells, each of which has data of all the specified things within or near it. The proposed method then retrieves only the data within or near the identified cells and performs the join only between the retrieved data. Consequently, compared with previous methods where the processing cost increases rapidly as the size of data or the number of things being joined increases, the processing cost is greatly reduced. The experimental results on a real IoT dataset show that the proposed method significantly reduces the execution time compared with the existing methods. INDEX TERMS Spatio-temporal join, spatio-temporal index, Internet of Things, IoT data
IL-18 production may enhance immune system defense against KG-1 cells ; NB4 cells, which are associated with good prognosis, do not produce IL-18. In this study, we treated KG-1 cells with IL-18 and used microarray technology to assess subsequent effects on gene expression. In UniGene-array of 7488 human genes, expression of 57 genes, including stress related genes, increased at least 2-fold, whereas expression of 48 genes decreased at least 2-fold.
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