The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformat...The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.展开更多
This paper proposes a single-ended fault detection scheme for long transmission lines using support vector machine(SVM)for multi-terminal direct current systems based on modular multilevel converter(MMC-MTDC).The sche...This paper proposes a single-ended fault detection scheme for long transmission lines using support vector machine(SVM)for multi-terminal direct current systems based on modular multilevel converter(MMC-MTDC).The scheme overcomes existing detection difficulties in the protection of long transmission lines resulting from high grounding resistance and attenuation,and also avoids the sophisticated process of threshold value selection.The high-frequency components in the measured voltage extracted by a wavelet transform and the amplitude of the zero-mode set of the positive-sequence voltage are the inputs to a trained SVM.The output of the SVM determines the fault type.A model of a four-terminal DC power grid with overhead transmission lines is built in PSCAD/EMTDC.Simulation results of EMTDC confirm that the proposed scheme achieves 100%accuracy in detecting short-circuit faults with high resistance on long transmission lines.The proposed scheme eliminates mal-operation of DC circuit breakers when faced with power order changes or AC-side faults.Its robustness and time delay are also assessed and shown to have no perceptible effect on the speed and accuracy of the detection scheme,thus ensuring its reliability and stability.展开更多
文摘The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.
文摘This paper proposes a single-ended fault detection scheme for long transmission lines using support vector machine(SVM)for multi-terminal direct current systems based on modular multilevel converter(MMC-MTDC).The scheme overcomes existing detection difficulties in the protection of long transmission lines resulting from high grounding resistance and attenuation,and also avoids the sophisticated process of threshold value selection.The high-frequency components in the measured voltage extracted by a wavelet transform and the amplitude of the zero-mode set of the positive-sequence voltage are the inputs to a trained SVM.The output of the SVM determines the fault type.A model of a four-terminal DC power grid with overhead transmission lines is built in PSCAD/EMTDC.Simulation results of EMTDC confirm that the proposed scheme achieves 100%accuracy in detecting short-circuit faults with high resistance on long transmission lines.The proposed scheme eliminates mal-operation of DC circuit breakers when faced with power order changes or AC-side faults.Its robustness and time delay are also assessed and shown to have no perceptible effect on the speed and accuracy of the detection scheme,thus ensuring its reliability and stability.
