We develop a new spectroscopic method to quickly and intuitively characterize the coupling of two microwave-photon-coupled semiconductor qubits via a high-impedance resonator.Highly distinctive and unique geometric pa...We develop a new spectroscopic method to quickly and intuitively characterize the coupling of two microwave-photon-coupled semiconductor qubits via a high-impedance resonator.Highly distinctive and unique geometric patterns are revealed as we tune the qubit tunnel couplings relative to the frequency of the mediating photons.These patterns are in excellent agreement with a simulation using the Tavis-Cummings model,and allow us to readily identify different parameter regimes for both qubits in the detuning space.This method could potentially be an important component in the overall spectroscopic toolbox for quickly characterizing certain collective properties of multiple cavity quantum electrodynamics(QED)coupled qubits.展开更多
Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be esti...Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be estimated based on limited clinical data,leading to instability of the final model.In the present study,we analyzed the predictive ability and applicability of a simplified quasi-steady state (QSS)model with the assumption that the total target concentration was a constant parameter during treatment with monoelonal antibody in clinical data modeling.Based on the parameters of a published TMDD model of denosumab,simulations were performed at population and individual levels.Then,a simplified TMDD model,QSS model, was used to examine the effects of hypotheses,in which the total receptor concentration was constant or variable on model fit and stability of parameter estimation.Both simulations at the population level and model fit results of simulated individual data showed that at the therapeutic doses,the total receptor concentration had little influence on changes in drug concentration,and the model with constant total receptor concentration had the same predictive power.The validated hypothesis could be applied to clinical trial design and selection of the optimal PK model in the development of monoclonal antibodies.展开更多
The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in v...The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in vivo functions of protein-polymer conjugates has not been well elucidated. Herein we report the effect of molecular weight of poly（oligo（ethylene glycol） methyl ether methacrylate） （POEGMA） on the in vitro and in vivo properties of C-termi- nal interferon-alpha （IFN）-POEGMA conjugates. Increasing the molecular weight of POEGMA decreased the in vitro activity of IFN-ct but increased its thermal stability and in vivo pharmacokinetics. Intriguingly, the in vivo antitumor efficacy of IFN-a was increased by increasing the POEGMA molecular weight from ca. 20 to 60 kDa, but was not further increased by increasing the molecular weight of POEGMA from ca. 60 to 100 kDa due to the neutralization of the improved pharmacokinetics and the reduced in vitro activity. This finding offers a new viewpoint on the molecular size rationale for designing next-generation protein-polymer conjugates, which may benefit patients by reducing admin- istration frequency and adverse reactions, and improving therapeutic efficacy.展开更多
基金supported by the National Key Research and Development Program of China(2016YFA0301700)the National Natural Science Foundation of China(61922074,11674300,61674132,11625419 and 11804327)+2 种基金the Strategic Priority Research Program of the CAS(XDB24030601)the Anhui Initiative in Quantum Information Technologies(AHY080000)financial support by U.S.ARO through Grant No.W911NF1410346 and No.W911NF1710257。
文摘We develop a new spectroscopic method to quickly and intuitively characterize the coupling of two microwave-photon-coupled semiconductor qubits via a high-impedance resonator.Highly distinctive and unique geometric patterns are revealed as we tune the qubit tunnel couplings relative to the frequency of the mediating photons.These patterns are in excellent agreement with a simulation using the Tavis-Cummings model,and allow us to readily identify different parameter regimes for both qubits in the detuning space.This method could potentially be an important component in the overall spectroscopic toolbox for quickly characterizing certain collective properties of multiple cavity quantum electrodynamics(QED)coupled qubits.
文摘Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal antibodies.However,there are too many parameters in full TMDD model to be estimated based on limited clinical data,leading to instability of the final model.In the present study,we analyzed the predictive ability and applicability of a simplified quasi-steady state (QSS)model with the assumption that the total target concentration was a constant parameter during treatment with monoelonal antibody in clinical data modeling.Based on the parameters of a published TMDD model of denosumab,simulations were performed at population and individual levels.Then,a simplified TMDD model,QSS model, was used to examine the effects of hypotheses,in which the total receptor concentration was constant or variable on model fit and stability of parameter estimation.Both simulations at the population level and model fit results of simulated individual data showed that at the therapeutic doses,the total receptor concentration had little influence on changes in drug concentration,and the model with constant total receptor concentration had the same predictive power.The validated hypothesis could be applied to clinical trial design and selection of the optimal PK model in the development of monoclonal antibodies.
基金financially supported by Grants from the National Natural Science Foundation of China (21274043 and 21534006).
文摘The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in vivo functions of protein-polymer conjugates has not been well elucidated. Herein we report the effect of molecular weight of poly（oligo（ethylene glycol） methyl ether methacrylate） （POEGMA） on the in vitro and in vivo properties of C-termi- nal interferon-alpha （IFN）-POEGMA conjugates. Increasing the molecular weight of POEGMA decreased the in vitro activity of IFN-ct but increased its thermal stability and in vivo pharmacokinetics. Intriguingly, the in vivo antitumor efficacy of IFN-a was increased by increasing the POEGMA molecular weight from ca. 20 to 60 kDa, but was not further increased by increasing the molecular weight of POEGMA from ca. 60 to 100 kDa due to the neutralization of the improved pharmacokinetics and the reduced in vitro activity. This finding offers a new viewpoint on the molecular size rationale for designing next-generation protein-polymer conjugates, which may benefit patients by reducing admin- istration frequency and adverse reactions, and improving therapeutic efficacy.
