In this article, the authors obtain some theoretical results for 2_(IV)^(m-p) designs to have the maximum number of clear two-factor interactions by considering the number of two-factor interactions that are not clear...In this article, the authors obtain some theoretical results for 2_(IV)^(m-p) designs to have the maximum number of clear two-factor interactions by considering the number of two-factor interactions that are not clear. Several 2_(IV)^(m-p) designs with the maximum number of clear two-factor interactions, judged using these results, are provided for illustration.展开更多
It is useful to know the maximum number of clear two-factor interactions in a 2Ⅲ^[m-（m-k）] design. This paper provides a method to construct a 2Ⅲ^[m-（m-k）] design with the maximum number of clear two-factor inte...It is useful to know the maximum number of clear two-factor interactions in a 2Ⅲ^[m-（m-k）] design. This paper provides a method to construct a 2Ⅲ^[m-（m-k）] design with the maximum number of clear two-factor interactions. And it is proved that the resulting designs have more dear two-factor interactions than those constructed by Tang et al. Moreover, the designs constructed are shown to have concise grid representations.展开更多
This article obtains some theoretical results on the number of clear two-factor interaction components and weak minimum aberration in an sm-pIVdesign, by considering the number of not clear two-factor interaction comp...This article obtains some theoretical results on the number of clear two-factor interaction components and weak minimum aberration in an sm-pIVdesign, by considering the number of not clear two-factor interaction components of the design.展开更多
目的:构建基于上皮间质相互作用蛋白1(epithelial-stromal interaction protein 1,EPSTI1)预后列线图预测肾透明细胞癌的预后。方法:回顾性分析2012年1月至2015年12月于福建医科大学附属第一医院221例接受手术治疗的肾透明细胞癌患者和T...目的:构建基于上皮间质相互作用蛋白1(epithelial-stromal interaction protein 1,EPSTI1)预后列线图预测肾透明细胞癌的预后。方法:回顾性分析2012年1月至2015年12月于福建医科大学附属第一医院221例接受手术治疗的肾透明细胞癌患者和TCGA数据库中533例肾透明细胞癌患者数据,对癌旁正常组织和癌组织标本进行免疫组织化学(immunohistochemistry,IHC)染色,分析EPSTI1的表达差异及与临床病理特征的相关性。对EPSTI1高表达与低表达患者的总生存期(overall survival,OS)和无病生存期(disease-free survival,DFS)进行Kaplan-Meier生存分析,采用单因素和多因素Cox比例风险模型分析OS的预后因素,进一步构建列线图模型并验证。结果:与癌旁正常肾组织比较,肾透明细胞癌组织中EPSTI1的IHC评分和m RNA表达水平均显著高于正常组织(均P<0.001),且在高T分期的癌组织中表达更高(P=0.036,P=0.006);EPSTI1蛋白表达与肿瘤最大径、TNM分期相关(P=0.002,P=0.032);EPSTI1低表达组OS、DFS均优于高表达组(P=0.046,P=0.003,P=0.001);单因素和多因素Cox回归分析结果显示,EPSTI1蛋白高表达、WHO/ISUP分级、AJCC/TNM分期是影响肾透明细胞癌患者预后不良的独立危险因素(P=0.009,P=0.039,P<0.001);基于上述变量构建的预后列线图模型对患者5年OS预测能力优于AJCC/TNM分期,校准曲线显示模型预测值与实际值间具有良好的一致性。结论:基于EPSTI1、AJCC/TNM分期和WHO/ISUP分级建立的列线图模型对肾透明细胞癌预后具有较强的预测能力。展开更多
Clear effects criterion is one of the important rules for selecting optimal fractional factorial designs,and it has become an active research issue in recent years.Tang et al.derived upper and lower bounds on the maxi...Clear effects criterion is one of the important rules for selecting optimal fractional factorial designs,and it has become an active research issue in recent years.Tang et al.derived upper and lower bounds on the maximum number of clear two-factor interactions(2fi's) in 2n-(n-k) fractional factorial designs of resolutions III and IV by constructing a 2n-(n-k) design for given k,which are only restricted for the symmetrical case.This paper proposes and studies the clear effects problem for the asymmetrical case.It improves the construction method of Tang et al.for 2n-(n-k) designs with resolution III and derives the upper and lower bounds on the maximum number of clear two-factor interaction components(2fic's) in 4m2n designs with resolutions III and IV.The lower bounds are achieved by constructing specific designs.Comparisons show that the number of clear 2fic's in the resulting design attains its maximum number in many cases,which reveals that the construction methods are satisfactory when they are used to construct 4m2n designs under the clear effects criterion.展开更多
The E3 ligase adaptor SPOP,overexpressed in the nucleus but frequently dislocated into the cytoplasm in all clear cell Renal Cell Carcinomas(ccRCC),serves as a regulatory hub to promote kidney cancer through the ubiqu...The E3 ligase adaptor SPOP,overexpressed in the nucleus but frequently dislocated into the cytoplasm in all clear cell Renal Cell Carcinomas(ccRCC),serves as a regulatory hub to promote kidney cancer through the ubiquitination and degradation of multiple downstream cancer proteins.Recently,our identification of a selective small-molecule inhibitor of the SPOP-phosphatase and tensin homolog(PTEN)interaction has demonstrated that the oncogenic SPOP-protein interaction would be a druggable target specific to ccRCC therapy.To our knowledge,this is the first time such a small-molecule inhibitor has been developed.Herein,we have identified a peptide binder for the SPOP-MATH domain that disrupts the oncogenic SPOP-protein interactions in kidney cancer cells.Computational design and biophysical characterization yielded peptide Pep38 that binds to the MATH domain of SPOP and competes on PTEN-binding to SPOP in vitro.The X-ray complex structure reveals that the peptide binder features the following combination:one,a mimic of the native peptide binder and two,an additionalβ-strand motif in sequence,which could contribute to increased binding affinity.In order to improve cellular permeability,we fused Pep38 with the delivery peptide TAT to prepare peptide TAT38,which inhibits the endogenous substrate binding to SPOP and suppresses the proliferation of the ccRCC cells.Our identification of the peptide inhibitors for SPOP-protein interactions provides further validation that the oncogenic SPOP-signaling pathway in ccRCC could be a druggable target specifically applicable to the therapy of kidney cancers.展开更多
基金Research supported by the NNSF of China (10301015: 10571093)the SRFDP of China (20050055038)the China Portdoctoral Science Foundation (20060390169)Liu and Zhang's research was also supported by the Visiting Scholar Program at Chern Institute of Mathematics.
文摘In this article, the authors obtain some theoretical results for 2_(IV)^(m-p) designs to have the maximum number of clear two-factor interactions by considering the number of two-factor interactions that are not clear. Several 2_(IV)^(m-p) designs with the maximum number of clear two-factor interactions, judged using these results, are provided for illustration.
基金Supported by the National Natural Science Foundation of China(No.10301015)
文摘It is useful to know the maximum number of clear two-factor interactions in a 2Ⅲ^[m-（m-k）] design. This paper provides a method to construct a 2Ⅲ^[m-（m-k）] design with the maximum number of clear two-factor interactions. And it is proved that the resulting designs have more dear two-factor interactions than those constructed by Tang et al. Moreover, the designs constructed are shown to have concise grid representations.
基金supported by the China Postdoctoral Science Foundation (20060390169)the Philosophy and Social Science Foundation of China (07CTJ002)+1 种基金the National Natural Science Foundation of China (10671099)Program for New Century Excellent Talents in University(NCET-08-0909)
文摘This article obtains some theoretical results on the number of clear two-factor interaction components and weak minimum aberration in an sm-pIVdesign, by considering the number of not clear two-factor interaction components of the design.
基金supported by the National Natural Science Foundation of China (Grant Nos. 10571093,10671099and 10771123)the Research Foundation for Doctor Programme (Grant No. 20050055038)+1 种基金the NaturalScience Foundation of Shandong Province of China (Grant No. Q2007A05)Zhang’s research was also supportedby the Visiting Scholar Program at Chern Institute of Mathematics
文摘Clear effects criterion is one of the important rules for selecting optimal fractional factorial designs,and it has become an active research issue in recent years.Tang et al.derived upper and lower bounds on the maximum number of clear two-factor interactions(2fi's) in 2n-(n-k) fractional factorial designs of resolutions III and IV by constructing a 2n-(n-k) design for given k,which are only restricted for the symmetrical case.This paper proposes and studies the clear effects problem for the asymmetrical case.It improves the construction method of Tang et al.for 2n-(n-k) designs with resolution III and derives the upper and lower bounds on the maximum number of clear two-factor interaction components(2fic's) in 4m2n designs with resolutions III and IV.The lower bounds are achieved by constructing specific designs.Comparisons show that the number of clear 2fic's in the resulting design attains its maximum number in many cases,which reveals that the construction methods are satisfactory when they are used to construct 4m2n designs under the clear effects criterion.
基金This work was supported by the National Natural Science Foundation of China(No.21725801 to C.-G.Y,Nos.81625022 and 81430084 to C,L,and No.21807103 to 2.D.)the National Key New Urug Lreation and Manufacturing Program,Ministry of Science and Technology(No.20182X09711002 to Z.D.)+1 种基金the Science and Technology Commis-sion of Shanghal munltlpallty(NB.18YF1428500 to Y.H.alu Nu..18431907100 to H.J.Jthe China Postdoctoral Science Foun-dation(No.2018M640434 to Y.H.,No.2017M621570 to Z.D.,and Nu.2018M032187 lwT.L).
文摘The E3 ligase adaptor SPOP,overexpressed in the nucleus but frequently dislocated into the cytoplasm in all clear cell Renal Cell Carcinomas(ccRCC),serves as a regulatory hub to promote kidney cancer through the ubiquitination and degradation of multiple downstream cancer proteins.Recently,our identification of a selective small-molecule inhibitor of the SPOP-phosphatase and tensin homolog(PTEN)interaction has demonstrated that the oncogenic SPOP-protein interaction would be a druggable target specific to ccRCC therapy.To our knowledge,this is the first time such a small-molecule inhibitor has been developed.Herein,we have identified a peptide binder for the SPOP-MATH domain that disrupts the oncogenic SPOP-protein interactions in kidney cancer cells.Computational design and biophysical characterization yielded peptide Pep38 that binds to the MATH domain of SPOP and competes on PTEN-binding to SPOP in vitro.The X-ray complex structure reveals that the peptide binder features the following combination:one,a mimic of the native peptide binder and two,an additionalβ-strand motif in sequence,which could contribute to increased binding affinity.In order to improve cellular permeability,we fused Pep38 with the delivery peptide TAT to prepare peptide TAT38,which inhibits the endogenous substrate binding to SPOP and suppresses the proliferation of the ccRCC cells.Our identification of the peptide inhibitors for SPOP-protein interactions provides further validation that the oncogenic SPOP-signaling pathway in ccRCC could be a druggable target specifically applicable to the therapy of kidney cancers.
