AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by compu...AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.展开更多
p63, known to play a role in development, has more recently also been implicated in cancer progression. Mutations in p63 have been shown to be responsible for several human developmental diseases. Differential splicin...p63, known to play a role in development, has more recently also been implicated in cancer progression. Mutations in p63 have been shown to be responsible for several human developmental diseases. Differential splicing of the p63 gene gives rise to p63 isoforms, which can act either as tumor suppressors or as oncogene. In this report, we studied the effects of naturally occurring TAp637 mutants on the regulation of p53/p63 and p63 specific target genes. We observed significant differences among p63 mutants to regulate the p53/p63 and p63 specific target genes. Additionally, we observed a differential effect of p63 mutants on wildtype-p63-mediated induction ofp53/p63 and p63 specific target genes. We also demonstrated that these mutants differentially regulate the binding of wildtype p63 to the promoter of target genes. Furthermore, the effects of these mutants on cell death and survival were consistent with their ability to regulate the downstream targets when compared to wildtype TAp63T. In summary, our data demonstrate that p63 mutants exhibit differential effects on p63 and p53/p63 specific target genes and on the induction of apoptosis, and provide further insight into the function of p63.展开更多
The flavor-changing neutral current (FCNC) problem at tree-level is a very critical defect of the two Higgs doublet extension of standard model (SM). In this article, a two-Higgs-doublet model (2HDM) in which such def...The flavor-changing neutral current (FCNC) problem at tree-level is a very critical defect of the two Higgs doublet extension of standard model (SM). In this article, a two-Higgs-doublet model (2HDM) in which such defects do not exist at all is to be demonstrated. The general pattern of matrix pairs which can be diagonalized simul-taneously by a same unitary transformation is proposed without extra constraints like symmetries or zeros in M matrices. Only an assumption of the hermiticity of mass matrices is employed in the derivation. With this assumption, number of parameters in the mass matrix of a specific fermion type is reduced from eighteen down to five. Eigenvalues and eigenvectors are analytically derived and it is surprising that unitary transformation matrix thus derived depends on only two parameters. It is a very general and elegant way to solve the tree-level FCNC problem radically and it includes previous similar models as special cases with specific parameter values.展开更多
In this work we present an analysis of a search for charged Higgs boson in the context of Two Doublet Higgs Model (2HDM) which is an extension of the Standard Model of particles physics where the 2HDM predicts by exis...In this work we present an analysis of a search for charged Higgs boson in the context of Two Doublet Higgs Model (2HDM) which is an extension of the Standard Model of particles physics where the 2HDM predicts by existence scalar sector with new five Higgs bosons;two of them are electrically charged and the other three Higgs bosons are neutral charged. Our analysis based on the Monte Carlo data produced from the simulation of 2HDM with proton antiproton collisions at the Tevatron = 1.96 TeV (Fermi Lab) and proton proton collisions at the LHC = 14 TeV (CERN) with final state includes electron, muon, multiple jets and missing transverse energy via the production and decay of the new Higgs in the hard process where the dominant background (electrons and muons) for this process comes from the Standard Model processes via the production and decay of top quark pair. We assumed that the branching ratio of charged Higgs boson to tau lepton and neutrino is 100%. We used the Artificial Neural Networks (ANNs) which are an efficient technique to discriminate the signal of charged Higgs boson from the SM background for charged Higgs boson masses between 80 GeV and 160 GeV. Also we calculated the production cross section at different energies, decay width, branching ration and different kinematics distribution for charged Higgs boson and for the final state particles.展开更多
The Dirac neutrino masses could be simply generated by a neutrinophilic scalar doublet with a vacuum being dramatically different from the electroweak one.While the case with an eV-scale vacuum has been widely explore...The Dirac neutrino masses could be simply generated by a neutrinophilic scalar doublet with a vacuum being dramatically different from the electroweak one.While the case with an eV-scale vacuum has been widely explored previously,we exploit in this work the desert where the scalar vacuum is of O(keV)scale.In this regime,there would be rare hope to probe the keV-vacuum neutrinophilic scalar model via the lepton-flavor-violating processes,which makes it distinguishable from the widely considered eV-scale vacuum.Although such a keV-vacuum scenario is inert in the low-energy flavor physics,we show that the baryogenesis realized via the lightest Dirac neutrino can be a natural candidate in explaining the baryon asymmetry of the Universe.Furthermore,the Dirac neutrinos with a keV-vacuum scalar can generate a shift of the effective neutrino number within the range 0.097≤ΔN_(eff)≤0.112,which can be probed by the future Simons Observatory experiments.In particular,the model with a minimal valueΔN_(eff)=0.097 can already be falsified by the future CMB Stage-Ⅳand Large Scale Structure surveys,providing consequently striking exploratory avenues in the cosmological regime for such a keV-vacuum scenario.展开更多
In this paper, charged Higgs pair production through l^＋l^- → H^＋ H^-, where l = e or μ, is studied within the framework of a general Two Higgs Doublet Model （2HDM）. The analysis is relevant to a future e^＋e^- ...In this paper, charged Higgs pair production through l^＋l^- → H^＋ H^-, where l = e or μ, is studied within the framework of a general Two Higgs Doublet Model （2HDM）. The analysis is relevant to a future e^＋e^- or μ^＋ μ^- collider operating at center of mass energy of √s = 500 GeV. Two different scenarios of small and large a values are studied. Here a is the parameter, which diagonMizes the neutral CP-even Higgs boson mass matrix. Within the Minimal Supersymmetric Standard Model （MSSM）, cross section of this process is almost the same at e＋ e- and #＋#- colliders. It is shown that at e^＋e^- eolliders within a general 2HDM, cross section is not sensitive to the mass of neutral Higgs bosons, however, it can acquire large values up to several picobarn at μ^＋μ^- colliders with the presence of heavy neutral Higgs bosons. A scan over Higgs boson mass parameter space is performed to analyze the effect of large masses of neutral Higgs bosons involved in the s-channel propagator and thus in the total cross section of this process.展开更多
In a previous paper by several of the authors a number of predictions were made in a study pertaining to the anomalous production of multiple leptons at the Large Hadron Collider(LHC). Discrepancies in multi-lepton fi...In a previous paper by several of the authors a number of predictions were made in a study pertaining to the anomalous production of multiple leptons at the Large Hadron Collider(LHC). Discrepancies in multi-lepton final states have become statistically compelling with the available Run 2 data. These could be connected with a heavy boson, H, which predominantly decays into a standard model Higgs boson, h, and a singlet scalar, S, where mH≈270 GeV and mS≈150 GeV. These can then be embedded into a scenario where a two-Higgs-doublet is considered with an additional singlet scalar, 2HDM+S. The long-standing discrepancy in the muon anomalous magnetic moment,△aμ, is interpreted in the context of the 2HDM+S type-II and type-X, along with additional fermionic degrees of freedom. The 2 HDM+S model alone, with constraints from the LHC data, does not seem to explain the △aμ anomaly.However, adding fermions with mass of order O(100) GeV can explain the discrepancy for sufficiently low values of fermion-scalar couplings.展开更多
Using the form factors calculated both in lattice QCD and HQET, we analyze the branching ratio, doublelepton polarization asymmetries and averaged double-lepton polarization asymmetries of Λ_b →Λμ^+μ^- decay in t...Using the form factors calculated both in lattice QCD and HQET, we analyze the branching ratio, doublelepton polarization asymmetries and averaged double-lepton polarization asymmetries of Λ_b →Λμ^+μ^- decay in the2 HDM Ⅲ, respectively. Combining the experimental constrains on the 2HDM Ⅲ parameters, we take two set of representative parameter spaces in our calculations. For the branching ratio of Λ+b →Λμμ-decay, considering the uncertainties of the form factors and input parameters, we find the results of both SM and 2HDM Ⅲ can satisfy the current experimental data in the framework of lattice QCD, but not in HQET. Then we calculate the double-lepton polarization asymmetries Pij and their averaged values Pij, we find the double-lepton polarization asymmetries PLT,PNN, and PTT are sensitive to the 2HDM Ⅲ. However, PLN, PNL, PNT, and PTN show the opposite results. The contribution of the 2HDM Ⅲ to their averaged values have similar results.展开更多
基金Supported by the China Key Program on Basic Research,G1998051102 and G1998051021 National Science Foundation of China, 39870862
文摘AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.
文摘p63, known to play a role in development, has more recently also been implicated in cancer progression. Mutations in p63 have been shown to be responsible for several human developmental diseases. Differential splicing of the p63 gene gives rise to p63 isoforms, which can act either as tumor suppressors or as oncogene. In this report, we studied the effects of naturally occurring TAp637 mutants on the regulation of p53/p63 and p63 specific target genes. We observed significant differences among p63 mutants to regulate the p53/p63 and p63 specific target genes. Additionally, we observed a differential effect of p63 mutants on wildtype-p63-mediated induction ofp53/p63 and p63 specific target genes. We also demonstrated that these mutants differentially regulate the binding of wildtype p63 to the promoter of target genes. Furthermore, the effects of these mutants on cell death and survival were consistent with their ability to regulate the downstream targets when compared to wildtype TAp63T. In summary, our data demonstrate that p63 mutants exhibit differential effects on p63 and p53/p63 specific target genes and on the induction of apoptosis, and provide further insight into the function of p63.
文摘The flavor-changing neutral current (FCNC) problem at tree-level is a very critical defect of the two Higgs doublet extension of standard model (SM). In this article, a two-Higgs-doublet model (2HDM) in which such defects do not exist at all is to be demonstrated. The general pattern of matrix pairs which can be diagonalized simul-taneously by a same unitary transformation is proposed without extra constraints like symmetries or zeros in M matrices. Only an assumption of the hermiticity of mass matrices is employed in the derivation. With this assumption, number of parameters in the mass matrix of a specific fermion type is reduced from eighteen down to five. Eigenvalues and eigenvectors are analytically derived and it is surprising that unitary transformation matrix thus derived depends on only two parameters. It is a very general and elegant way to solve the tree-level FCNC problem radically and it includes previous similar models as special cases with specific parameter values.
文摘In this work we present an analysis of a search for charged Higgs boson in the context of Two Doublet Higgs Model (2HDM) which is an extension of the Standard Model of particles physics where the 2HDM predicts by existence scalar sector with new five Higgs bosons;two of them are electrically charged and the other three Higgs bosons are neutral charged. Our analysis based on the Monte Carlo data produced from the simulation of 2HDM with proton antiproton collisions at the Tevatron = 1.96 TeV (Fermi Lab) and proton proton collisions at the LHC = 14 TeV (CERN) with final state includes electron, muon, multiple jets and missing transverse energy via the production and decay of the new Higgs in the hard process where the dominant background (electrons and muons) for this process comes from the Standard Model processes via the production and decay of top quark pair. We assumed that the branching ratio of charged Higgs boson to tau lepton and neutrino is 100%. We used the Artificial Neural Networks (ANNs) which are an efficient technique to discriminate the signal of charged Higgs boson from the SM background for charged Higgs boson masses between 80 GeV and 160 GeV. Also we calculated the production cross section at different energies, decay width, branching ration and different kinematics distribution for charged Higgs boson and for the final state particles.
基金Supported by the National Natural Science Foundation of China(12135006,12075097,12047527,11775092)by the Fundamental Research Funds for the Central Universities(CCNU20TS007,CCNU19TD012,CCNU22LJ004)。
文摘The Dirac neutrino masses could be simply generated by a neutrinophilic scalar doublet with a vacuum being dramatically different from the electroweak one.While the case with an eV-scale vacuum has been widely explored previously,we exploit in this work the desert where the scalar vacuum is of O(keV)scale.In this regime,there would be rare hope to probe the keV-vacuum neutrinophilic scalar model via the lepton-flavor-violating processes,which makes it distinguishable from the widely considered eV-scale vacuum.Although such a keV-vacuum scenario is inert in the low-energy flavor physics,we show that the baryogenesis realized via the lightest Dirac neutrino can be a natural candidate in explaining the baryon asymmetry of the Universe.Furthermore,the Dirac neutrinos with a keV-vacuum scalar can generate a shift of the effective neutrino number within the range 0.097≤ΔN_(eff)≤0.112,which can be probed by the future Simons Observatory experiments.In particular,the model with a minimal valueΔN_(eff)=0.097 can already be falsified by the future CMB Stage-Ⅳand Large Scale Structure surveys,providing consequently striking exploratory avenues in the cosmological regime for such a keV-vacuum scenario.
文摘In this paper, charged Higgs pair production through l^＋l^- → H^＋ H^-, where l = e or μ, is studied within the framework of a general Two Higgs Doublet Model （2HDM）. The analysis is relevant to a future e^＋e^- or μ^＋ μ^- collider operating at center of mass energy of √s = 500 GeV. Two different scenarios of small and large a values are studied. Here a is the parameter, which diagonMizes the neutral CP-even Higgs boson mass matrix. Within the Minimal Supersymmetric Standard Model （MSSM）, cross section of this process is almost the same at e＋ e- and #＋#- colliders. It is shown that at e^＋e^- eolliders within a general 2HDM, cross section is not sensitive to the mass of neutral Higgs bosons, however, it can acquire large values up to several picobarn at μ^＋μ^- colliders with the presence of heavy neutral Higgs bosons. A scan over Higgs boson mass parameter space is performed to analyze the effect of large masses of neutral Higgs bosons involved in the s-channel propagator and thus in the total cross section of this process.
基金the support from the South African Department of Science and Innovation through the SA-CERN programthe National Research Foundation for various forms of support
文摘In a previous paper by several of the authors a number of predictions were made in a study pertaining to the anomalous production of multiple leptons at the Large Hadron Collider(LHC). Discrepancies in multi-lepton final states have become statistically compelling with the available Run 2 data. These could be connected with a heavy boson, H, which predominantly decays into a standard model Higgs boson, h, and a singlet scalar, S, where mH≈270 GeV and mS≈150 GeV. These can then be embedded into a scenario where a two-Higgs-doublet is considered with an additional singlet scalar, 2HDM+S. The long-standing discrepancy in the muon anomalous magnetic moment,△aμ, is interpreted in the context of the 2HDM+S type-II and type-X, along with additional fermionic degrees of freedom. The 2 HDM+S model alone, with constraints from the LHC data, does not seem to explain the △aμ anomaly.However, adding fermions with mass of order O(100) GeV can explain the discrepancy for sufficiently low values of fermion-scalar couplings.
基金Supported by the National Natural Science Foundation of China under Grant Nos.11345005Key Scientific Research projects of Henan Educational Committee(13A140814)the National Science Foundation under Grant No.U1332103
文摘Using the form factors calculated both in lattice QCD and HQET, we analyze the branching ratio, doublelepton polarization asymmetries and averaged double-lepton polarization asymmetries of Λ_b →Λμ^+μ^- decay in the2 HDM Ⅲ, respectively. Combining the experimental constrains on the 2HDM Ⅲ parameters, we take two set of representative parameter spaces in our calculations. For the branching ratio of Λ+b →Λμμ-decay, considering the uncertainties of the form factors and input parameters, we find the results of both SM and 2HDM Ⅲ can satisfy the current experimental data in the framework of lattice QCD, but not in HQET. Then we calculate the double-lepton polarization asymmetries Pij and their averaged values Pij, we find the double-lepton polarization asymmetries PLT,PNN, and PTT are sensitive to the 2HDM Ⅲ. However, PLN, PNL, PNT, and PTN show the opposite results. The contribution of the 2HDM Ⅲ to their averaged values have similar results.
