Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulator...Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulatory transcriptional loop.The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes.Our in silico analysis of HNF1A,HNF4A.and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrich-ment of these transcription factors specifically in the liver.Our previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma glycoproteins.Here,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype.We used the state-of-the-art clus-tered regularly interspaced short palindromic repeats/dead Cas9(CRISPR/dCas9)molecular tool for the downregulation of the HNF1A,HNF4A,and FOXA2 genes in HepG2 cells-a human liver cancer cell line.The results show that the downregulation of all three genes individually and in pairs affects the transcrip-tional activity of many glyco-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures.The effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantennary glycans.We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure.We also propose a model showing feedback loops with the mutual activation of HNF1A-FOXA2 and HNF4A-FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.展开更多
Existence and regularity of solutions to model for liquid mixture of 3He-4He is considered in this paper. First, it is proved that this system possesses a unique global weak solution in H^1 （Ω, C ×R） by using ...Existence and regularity of solutions to model for liquid mixture of 3He-4He is considered in this paper. First, it is proved that this system possesses a unique global weak solution in H^1 （Ω, C ×R） by using Galerkin method. Secondly, by using an iteration procedure, regularity estimates for the linear semigroups, it is proved that the model for liquid mixture of 3He-4He has a unique solution in H^k（Ω, C × R） for all k ≥ 1.展开更多
In this article the rooted planar near-4-regular Eulerian trails are enum erated and an explicit form ula for such m aps is presented. Further, the rooted near-4-regular Eulerian m aps on the torus are counted in an...In this article the rooted planar near-4-regular Eulerian trails are enum erated and an explicit form ula for such m aps is presented. Further, the rooted near-4-regular Eulerian m aps on the torus are counted in an exact w ay.展开更多
In this paper we present and test a numerical method for computing eigenvalues of 4th order Sturm-Liouville (SL) differential operators on finite intervals with regular boundary conditions. This method is a 4th order ...In this paper we present and test a numerical method for computing eigenvalues of 4th order Sturm-Liouville (SL) differential operators on finite intervals with regular boundary conditions. This method is a 4th order shooting method based on Magnus expansions (MG4) which use MG4 shooting as the integrator. This method is similar to the SLEUTH (Sturm-Liouville Eigenvalues Using Theta Matrices) method of Greenberg and Marletta which uses the 2nd order Pruess method (also known as the MG2 shooting method) for the integrator. This method often achieves near machine precision accuracies, and some comparisons of its performance against the well-known SLEUTH software package are presented.展开更多
Previous mining excavation in upper sublevels left several mined-out areas in Haigou gold mine. To ensure safety of the main and auxiliary shafts and mining production in deeper sublevels, systematical studies on regu...Previous mining excavation in upper sublevels left several mined-out areas in Haigou gold mine. To ensure safety of the main and auxiliary shafts and mining production in deeper sublevels, systematical studies on regularity, prediction, and control of ground pressure in the mine were carried out. Through 3D-numerical modeling and in-situ monitoring of acoustic emission, pressure and displacement, the ground pressure activity and the stability status of surrounding rock masses and the two shafts were assessed. Based on in-situ monitoring practice in Haigou mine,4 modes to judge rock stability according to the monitoring information of acoustic emission,pressure,and displacement were presented.展开更多
基金the European Structural and Investment Funded Grant"Cardio Metabolic"(#KK.01.2.1.02.0321)the Croatian National Centre of Research Excellence in Personalized Healthcare Grant(#KK.01.1.1.01.0010)+2 种基金the European Regional Development Fund Grant,project"CRISPR/Cas9-CasMouse"(#KK.01.1.1.04.0085)the European Structural and Investment Funded Project of Centre of Competence in Molecular Diagnostics(#KK.01.2.2.03.0006)the Croatian National Centre of Research Excellence in Personalized Healthcare Grant(#KK.01.1.1.01.0010).
文摘Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulatory transcriptional loop.The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes.Our in silico analysis of HNF1A,HNF4A.and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrich-ment of these transcription factors specifically in the liver.Our previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma glycoproteins.Here,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype.We used the state-of-the-art clus-tered regularly interspaced short palindromic repeats/dead Cas9(CRISPR/dCas9)molecular tool for the downregulation of the HNF1A,HNF4A,and FOXA2 genes in HepG2 cells-a human liver cancer cell line.The results show that the downregulation of all three genes individually and in pairs affects the transcrip-tional activity of many glyco-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures.The effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantennary glycans.We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure.We also propose a model showing feedback loops with the mutual activation of HNF1A-FOXA2 and HNF4A-FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.
基金Sponsored by the National Natural Science Foundation of China(11071177)NSF of Sichuan Science and Technology Department of China(2010JY0057)the NSF of Sichuan Education Department of China(11ZA102)
文摘Existence and regularity of solutions to model for liquid mixture of 3He-4He is considered in this paper. First, it is proved that this system possesses a unique global weak solution in H^1 （Ω, C ×R） by using Galerkin method. Secondly, by using an iteration procedure, regularity estimates for the linear semigroups, it is proved that the model for liquid mixture of 3He-4He has a unique solution in H^k（Ω, C × R） for all k ≥ 1.
文摘In this article the rooted planar near-4-regular Eulerian trails are enum erated and an explicit form ula for such m aps is presented. Further, the rooted near-4-regular Eulerian m aps on the torus are counted in an exact w ay.
文摘In this paper we present and test a numerical method for computing eigenvalues of 4th order Sturm-Liouville (SL) differential operators on finite intervals with regular boundary conditions. This method is a 4th order shooting method based on Magnus expansions (MG4) which use MG4 shooting as the integrator. This method is similar to the SLEUTH (Sturm-Liouville Eigenvalues Using Theta Matrices) method of Greenberg and Marletta which uses the 2nd order Pruess method (also known as the MG2 shooting method) for the integrator. This method often achieves near machine precision accuracies, and some comparisons of its performance against the well-known SLEUTH software package are presented.
基金the National Key Technologies R&D Program of China (No. 2006BAK04B02)
文摘Previous mining excavation in upper sublevels left several mined-out areas in Haigou gold mine. To ensure safety of the main and auxiliary shafts and mining production in deeper sublevels, systematical studies on regularity, prediction, and control of ground pressure in the mine were carried out. Through 3D-numerical modeling and in-situ monitoring of acoustic emission, pressure and displacement, the ground pressure activity and the stability status of surrounding rock masses and the two shafts were assessed. Based on in-situ monitoring practice in Haigou mine,4 modes to judge rock stability according to the monitoring information of acoustic emission,pressure,and displacement were presented.
