Hypoxia and aberrant activation of epidermal growth factor receptor(EGFR)are considered important features of various malignancies.However,whether hypoxia can directly trigger EGFR activation and its clinical implicat...Hypoxia and aberrant activation of epidermal growth factor receptor(EGFR)are considered important features of various malignancies.However,whether hypoxia can directly trigger EGFR activation and its clinical implications remain unclear.In this study,we demonstrated that in oral cancer,a typical hypoxic tumor,hypoxia can induce chronic but constitutive phosphorylation of wild-type EGFR in the absence of ligands.Oral cancer cell lines exhibit different EGFR phosphorylation responses to hypoxia.In hypoxic HN4 and HN6 cells,ubiquitination-mediated endocytosis,lysosomal sorting,and degradation lead to low levels of EGFR phosphorylation.However,in CAL-27 and HN30 cells,a novel HIF-1α-induced long noncoding RNA(lnc RNA),EUDAL,can compete with the E3 ligase/adaptor complex c-Cbl/Grb2 for binding to EGFR,stabilizing phosphorylated EGFR(p EGFR)and resulting in sustained activation of EGFR and its downstream STAT3/BNIP3 signaling.STAT3/BNIP3-mediated autophagy leads to antitumor drug resistance.A high EUDAL/EGFR/STAT3/autophagy pathway activation predicts poor response to chemotherapy in oral cancer patients.Collectively,hypoxia can induce noncanonical ligand-independent EGFR phosphorylation.High EUDAL expression facilitates sustained EGFR phosphorylation in hypoxic tumor cells and leads to autophagy-related drug resistance.展开更多
For better controllability in actuations,it is desirable to create Functionally Graded Shape Memory Alloys（FG-SMAs）in the actuation direction.It can be achieved by applying different heat treatment processes to crea...For better controllability in actuations,it is desirable to create Functionally Graded Shape Memory Alloys（FG-SMAs）in the actuation direction.It can be achieved by applying different heat treatment processes to create the gradient along the radius of a SMA cylinder.Analytical solutions are derived to predict the macroscopic behaviors of such a functionally graded SMA cylinder.The Tresca yield criterion and linear hardening are used to describe the different phase transformations with different gradient parameters.The numerical results for an example of the model exhibit different pseudo-elastic behaviors from the non-gradient case,as well as a variational hysteresis loop for the transformation,providing a mechanism for easy actuation control.When the gradient disappears,the model can degenerate to the non-gradient case.展开更多
A shape hardening function is developed that improves the predictive capabilities of the generalized bounding surface model for cohesive soils, especially when applied to overconsolidated specimens. This improvement i...A shape hardening function is developed that improves the predictive capabilities of the generalized bounding surface model for cohesive soils, especially when applied to overconsolidated specimens. This improvement is realized without any changes to the simple elliptical shape of the bounding surface, and actually reduces the number of parameters associated with the model by one.展开更多
基金supported by the National Natural Science Foundation of China(82273095,82203614)the Shanghai Sailing Program(22YF1421600)。
文摘Hypoxia and aberrant activation of epidermal growth factor receptor(EGFR)are considered important features of various malignancies.However,whether hypoxia can directly trigger EGFR activation and its clinical implications remain unclear.In this study,we demonstrated that in oral cancer,a typical hypoxic tumor,hypoxia can induce chronic but constitutive phosphorylation of wild-type EGFR in the absence of ligands.Oral cancer cell lines exhibit different EGFR phosphorylation responses to hypoxia.In hypoxic HN4 and HN6 cells,ubiquitination-mediated endocytosis,lysosomal sorting,and degradation lead to low levels of EGFR phosphorylation.However,in CAL-27 and HN30 cells,a novel HIF-1α-induced long noncoding RNA(lnc RNA),EUDAL,can compete with the E3 ligase/adaptor complex c-Cbl/Grb2 for binding to EGFR,stabilizing phosphorylated EGFR(p EGFR)and resulting in sustained activation of EGFR and its downstream STAT3/BNIP3 signaling.STAT3/BNIP3-mediated autophagy leads to antitumor drug resistance.A high EUDAL/EGFR/STAT3/autophagy pathway activation predicts poor response to chemotherapy in oral cancer patients.Collectively,hypoxia can induce noncanonical ligand-independent EGFR phosphorylation.High EUDAL expression facilitates sustained EGFR phosphorylation in hypoxic tumor cells and leads to autophagy-related drug resistance.
基金the financial support of National Natural Science Foundation of China (no.11502284, 51505483, 11772041)the Fundamental Research Funds for the Central Universities (3122016C006) of China
文摘For better controllability in actuations,it is desirable to create Functionally Graded Shape Memory Alloys（FG-SMAs）in the actuation direction.It can be achieved by applying different heat treatment processes to create the gradient along the radius of a SMA cylinder.Analytical solutions are derived to predict the macroscopic behaviors of such a functionally graded SMA cylinder.The Tresca yield criterion and linear hardening are used to describe the different phase transformations with different gradient parameters.The numerical results for an example of the model exhibit different pseudo-elastic behaviors from the non-gradient case,as well as a variational hysteresis loop for the transformation,providing a mechanism for easy actuation control.When the gradient disappears,the model can degenerate to the non-gradient case.
基金supported by the Fulbright Colombia-Colciencias Scholarship and Universidad Militar Nueva Granada
文摘A shape hardening function is developed that improves the predictive capabilities of the generalized bounding surface model for cohesive soils, especially when applied to overconsolidated specimens. This improvement is realized without any changes to the simple elliptical shape of the bounding surface, and actually reduces the number of parameters associated with the model by one.
