Objective: To provide a kinetic model(s) and reveal the mechanism of thymoquinone and Poloxin blocking an emerging anti-cancer target, human Polo-like kinase 1 (hPlkl) Polo-box domain (PBD). Methods: The bindi...Objective: To provide a kinetic model(s) and reveal the mechanism of thymoquinone and Poloxin blocking an emerging anti-cancer target, human Polo-like kinase 1 (hPlkl) Polo-box domain (PBD). Methods: The binding kinetics was determined by using a fluorescence polarization based assay. The putative mechanism was examined with a competition test. Results: Thymoquinone follows a one-step binding with an association rate constant (k1) of 6.635× 10^3 L.mol^-1 min^-1.Poloxin fit a two-step binding with a dissociation constant (Ki) of 118 μmol/L for the intermediate complex and its isomerization rate (k4) of 0.131 5 minJ to form an irreversible adduct. No significant dissociation was observed for either ligand up to 13 h. The inhibitors responded insignificantly to the presence of Michael donors as hPIkl-PBD competitors. Conclusion: Thymoquinone and Poloxin are slow-tight ligands to the hPlkl-PBD with kinetic models distinct from each other. Michael addition as the mechanism is excluded.展开更多
A generic numerical model of a long-wavelength Avalanche Photodiode (APD) based on narrow bandgap semiconductor InAsSb on InAs substrate is reported for the first time. This model has been applied for theoretical ch...A generic numerical model of a long-wavelength Avalanche Photodiode (APD) based on narrow bandgap semiconductor InAsSb on InAs substrate is reported for the first time. This model has been applied for theoretical characterization of a proposed N^+ InAS/P-InAsSb avalanche photodiode structure for possible application in 2-5 μm wavelength region. The parameters such as gain, excess noise factor and their trade-off with variation of doping concentration and bias voltage have been estimated for the APD taking into account history-dependent theory of avalanche multiplication process, The LWIR APD is expected to fred application in optical gas sensor and in future generation of optical communication system.展开更多
基金a co-sponsored graduate research project by China Pharmaceutical University and Shanghai Medicilon Inc
文摘Objective: To provide a kinetic model(s) and reveal the mechanism of thymoquinone and Poloxin blocking an emerging anti-cancer target, human Polo-like kinase 1 (hPlkl) Polo-box domain (PBD). Methods: The binding kinetics was determined by using a fluorescence polarization based assay. The putative mechanism was examined with a competition test. Results: Thymoquinone follows a one-step binding with an association rate constant (k1) of 6.635× 10^3 L.mol^-1 min^-1.Poloxin fit a two-step binding with a dissociation constant (Ki) of 118 μmol/L for the intermediate complex and its isomerization rate (k4) of 0.131 5 minJ to form an irreversible adduct. No significant dissociation was observed for either ligand up to 13 h. The inhibitors responded insignificantly to the presence of Michael donors as hPIkl-PBD competitors. Conclusion: Thymoquinone and Poloxin are slow-tight ligands to the hPlkl-PBD with kinetic models distinct from each other. Michael addition as the mechanism is excluded.
文摘A generic numerical model of a long-wavelength Avalanche Photodiode (APD) based on narrow bandgap semiconductor InAsSb on InAs substrate is reported for the first time. This model has been applied for theoretical characterization of a proposed N^+ InAS/P-InAsSb avalanche photodiode structure for possible application in 2-5 μm wavelength region. The parameters such as gain, excess noise factor and their trade-off with variation of doping concentration and bias voltage have been estimated for the APD taking into account history-dependent theory of avalanche multiplication process, The LWIR APD is expected to fred application in optical gas sensor and in future generation of optical communication system.