Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three ...lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.
Algorithms increasingly make managerial decisions that people used to make. Perceptions of algorithms, regardless of the algorithms' actual performance, can significantly influence their adoption, ...yet we do not fully understand how people perceive decisions made by algorithms as compared with decisions made by humans. To explore perceptions of algorithmic management, we conducted an online experiment using four managerial decisions that required either mechanical or human skills. We manipulated the decision-maker (algorithmic or human), and measured perceived fairness, trust, and emotional response. With the mechanical tasks, algorithmic and human-made decisions were perceived as equally fair and trustworthy and evoked similar emotions; however, human managers' fairness and trustworthiness were attributed to the manager's authority, whereas algorithms' fairness and trustworthiness were attributed to their perceived efficiency and objectivity. Human decisions evoked some positive emotion due to the possibility of social recognition, whereas algorithmic decisions generated a more mixed response – algorithms were seen as helpful tools but also possible tracking mechanisms. With the human tasks, algorithmic decisions were perceived as less fair and trustworthy and evoked more negative emotion than human decisions. Algorithms' perceived lack of intuition and subjective judgment capabilities contributed to the lower fairness and trustworthiness judgments. Positive emotion from human decisions was attributed to social recognition, while negative emotion from algorithmic decisions was attributed to the dehumanizing experience of being evaluated by machines. This work reveals people's lay concepts of algorithmic versus human decisions in a management context and suggests that task characteristics matter in understanding people's experiences with algorithmic technologies.
A circuit for balancing Li-ion battery cells is proposed. This circuit requires one small transformer and N + 3 bilateral switches to equalize the charging states of N serially connected battery ...cells. The transformer works as an energy carrier, and the switches select two unbalanced cells that require an energy transfer from one to the other cell. The circuit was tested for a 12-cell Li-ion battery under static, cyclic, and dynamic charging/discharging conditions. Under static condition, the power-transfer efficiency was measured as 80.4% at a balancing power of 0.78 W; two 4400-mA·h battery cells at a state of charge (SOC) = 70 and 80% were equalized after 78 min. The results of cyclic and dynamic charging/discharging conditions show that the circuit is appropriate for balancing the Li-ion battery cells for vehicles and energy storage systems.
A modularized design of an active charge equalizer and a charge equalization algorithm for a Li-ion battery pack are proposed in this paper. The equalizer consists of one module-balancing circuit and ...M cell-balancing circuits, where M is the number of modules in the battery pack. Each balancing circuit uses an inductor that is placed in a bridge of four bidirectional switches and works as an energy carrier, and uses a cell/module access network that enables energy transfer from one cell/module to another cell or module. The charge equalization between modules can be performed simultaneously with that between cells, so the proposed circuit can significantly reduce the time required to equalize the charges of all cells in the battery pack. The proposed circuit was tested under various charging/discharging conditions for a battery pack composed of four serially connected modules, with four serially connected cells per module. Experimental results show that the proposed circuit and algorithm comprise a good solution to balance a Li-ion battery pack.
Although tetraarsenic hexoxide is known to exert an anti-tumor effect by inducing apoptosis in various cancer cells, its effect on other forms of regulated cell death remains unclear. Here, we show ...that tetraarsenic hexoxide induces the pyroptotic cell death through activation of mitochondrial reactive oxygen species (ROS)-mediated caspase-3/gasdermin E (GSDME) pathway, thereby suppressing tumor growth and metastasis of triple-negative breast cancer (TNBC) cells. Interestingly, tetraarsenic hexoxide-treated TNBC cells exhibited specific pyroptotic characteristics, including cell swelling, balloon-like bubbling, and LDH releases through pore formation in the plasma membrane, eventually suppressing tumor formation and lung metastasis of TNBC cells. Mechanistically, tetraarsenic hexoxide markedly enhanced the production of mitochondrial ROS by inhibiting phosphorylation of mitochondrial STAT3, subsequently inducing caspase-3-dependent cleavage of GSDME, which consequently promoted pyroptotic cell death in TNBC cells. Collectively, our findings highlight tetraarsenic hexoxide-induced pyroptosis as a new therapeutic strategy that may inhibit cancer progression of TNBC cells.
Dental measurements have been commonly taken from plaster dental models obtained from alginate impressions can. Through the use of an intraoral scanner, digital impressions now acquire the ...information directly from the mouth. The purpose of this study was to determine the validity of the intraoral scans compared to plaster models.
Two types of dental models (intraoral scan and plaster model) of 20 subjects were included in this study. The subjects had impressions taken of their teeth and made as plaster model. In addition, their mouths were scanned with the intraoral scanner and the scans were converted into digital models. Eight transverse and 16 anteroposterior measurements, 24 tooth heights and widths were recorded on the plaster models with a digital caliper and on the intraoral scan with 3D reverse engineering software. For 3D surface analysis, the two models were superimposed by using best-fit algorithm. The average differences between the two models at all points on the surfaces were computed. Paired t-test and Bland-Altman plot were used to determine the validity of measurements from the intraoral scan compared to those from the plaster model.
There were no significant differences between the plaster models and intraoral scans, except for one measurement of lower intermolar width. The Bland-Altman plots of all measurements showed that differences between the two models were within the limits of agreement. The average surface difference between the two models was within 0.10 mm.
The results of the present study indicate that the intraoral scans are clinically acceptable for diagnosis and treatment planning in dentistry and can be used in place of plaster models.
Hybrid organic–inorganic perovskite semiconductors have shown potential to develop into a new generation of light‐emitting diode (LED) technology. Herein, an important design principle for perovskite ...LEDs is elucidated regarding optimal perovskite thickness. Adopting a thin perovskite layer in the range of 35–40 nm is shown to be critical for both device efficiency and stability improvements. Maximum external quantum efficiencies (EQEs) of 17.6% for Cs0.2FA0.8PbI2.8Br0.2, 14.3% for CH3NH3PbI3 (MAPbI3), 10.1% for formamidinium lead iodide (FAPbI3), and 11.3% for formamidinium lead bromide (FAPbBr3)‐based LEDs are demonstrated with optimized perovskite layer thickness. Optical simulations show that the improved EQEs source from improved light outcoupling. Furthermore, elevated device temperature caused by Joule heating is shown as an important factor contributing to device degradation, and that thin perovskite emitting layers maintain lower junction temperature during operation and thus demonstrate increased stability.
An important design principle for perovskite light‐emitting diodes is discovered regarding optimal perovskite thickness. Adopting a thinner perovskite layer is beneficial for both device efficiency and stability, with external quantum efficiency (EQE) as high as 17.6% being achieved. The improved EQE is primarily due to better light outcoupling, and the improved stability is correlated with reduced Joule heating.
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