In this article, we investigate the existence of periodic solutions for a class of nonautonomous second-order differential systems with p(t)-Laplacian. Some multiplicity results are obtained by using critical point th...In this article, we investigate the existence of periodic solutions for a class of nonautonomous second-order differential systems with p(t)-Laplacian. Some multiplicity results are obtained by using critical point theory, which extend some known results.展开更多
The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At...The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.展开更多
We study a nonlinear periodic problem driven by the p（t）-Laplacian and having a nonsmooth potential （hemivariational inequalities）. Using a variational method based on nonsmooth critical point theory for locally L...We study a nonlinear periodic problem driven by the p（t）-Laplacian and having a nonsmooth potential （hemivariational inequalities）. Using a variational method based on nonsmooth critical point theory for locally Lipschitz functions, we first prove the existence of at least two nontrivial solutions under the generalized subquadratic and then establish the existence of at least one nontrivial solution under the generalized superquadratic.展开更多
基金Supported by the Natural Science Foundation of Anhui Province（1408085MA02, 1208085 MA13, 1308085MA01, 1308085QA15） Supported by the Key Foundation of Anhui Education Bureau （KJ2012A019, KJ2013A028）+2 种基金 Supported by the National Natural Science Foundation of China（11271371, 11301 004） Supported by the Research Fund for the Doctoral Program of Higher Education（20113401110001） Supported by 211 Project of Anhui University（02303129, 02303303-33030011, 02303902-39020011, KYXL2012004 XJYJXKC04, yfcl00012）
文摘In this article, we investigate the existence of periodic solutions for a class of nonautonomous second-order differential systems with p(t)-Laplacian. Some multiplicity results are obtained by using critical point theory, which extend some known results.
基金funded by the Ministry of Science and Higher Education of the Russian Federation(Grant No.075-15-2020-795 of 29.09.2020,unique project ID:RF-190220X0027).
文摘The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.
基金supported by the National Science Foundation of China (11001063, 10971043)the Fundamental Research Funds for the Central Universities (HEUCF 20111134)+2 种基金China Postdoctoral Science Foundation Funded Project (20110491032)Heilongjiang Provincial Science Foundation for Distinguished Young Scholars (JC200810)Program of Excellent Team in Harbin Institute of Technology and the Natural Science Foundation of Heilongjiang Province (A200803)
文摘We study a nonlinear periodic problem driven by the p（t）-Laplacian and having a nonsmooth potential （hemivariational inequalities）. Using a variational method based on nonsmooth critical point theory for locally Lipschitz functions, we first prove the existence of at least two nontrivial solutions under the generalized subquadratic and then establish the existence of at least one nontrivial solution under the generalized superquadratic.
基金Supported by the National Natural Science Foundation of China (11761038)Science and Technology Project of Department of Education of Jiangxi Province (GJJ180583)。
