交流潮流约束下的机组组合问题（AC power flow constrained unit commitment,ACUC）是一个非凸的混合整数非线性规划问题,包含大规模的离散变量,极难求解。该文建立了ACUC的分离式模型,引入部分代理割方法,提出了一种新的求解UC问题的...交流潮流约束下的机组组合问题（AC power flow constrained unit commitment,ACUC）是一个非凸的混合整数非线性规划问题,包含大规模的离散变量,极难求解。该文建立了ACUC的分离式模型,引入部分代理割方法,提出了一种新的求解UC问题的分解式算法。并在原始部分代理割（partial surrogate cuts,PSC）法的基础上,为避免在问题规模扩大时过早陷入局部最优解,结合电力系统特征,提出了引入直流潮流相关约束的改进PSC算法,改善解的质量。通过对6节点、IEEE 39节点和118节点系统的仿真计算验证了方法的有效性和适用性,在与其他算法的对比中突显了速度和精度上的优势。展开更多
In this paper,we are interested in HSS preconditioners for saddle point lin- ear systems with a nonzero(2,2)-th block.We study an approximation of the spectra of HSS preconditioned matrices and use these results to il...In this paper,we are interested in HSS preconditioners for saddle point lin- ear systems with a nonzero(2,2)-th block.We study an approximation of the spectra of HSS preconditioned matrices and use these results to illustrate and explain the spectra obtained from numerical examples,where the previous spectral analysis of HSS precon- ditioned matrices does not cover.展开更多
The human body consists of several physiological barriers that express a number of membrane transporters. For an orally absorbed drug the intestinal, hepatic, renal and blood-brain barriers are of the greatest importa...The human body consists of several physiological barriers that express a number of membrane transporters. For an orally absorbed drug the intestinal, hepatic, renal and blood-brain barriers are of the greatest importance. The ATP-binding cassette(ABC) transporters that mediate cellular efflux and the solute carrier transporters that mostly mediate cellular uptake are the two superfamilies responsible for membrane transport of vast majority of drugs and drug metabolites. The total number of human transporters in the two superfamilies exceeds 400, and about 40-50 transporters have been characterized for drug transport. The latest Food and Drug Administration guidance focuses on P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide 1B1(OATP1B1), OATP1B3, organic cation transporter 2(OCT2), and organic anion transporters 1(OAT1) and OAT3. The European Medicines Agency's shortlist additionally contains the bile salt export pump, OCT1, and the multidrug and toxin extrusion transporters, multidrug and toxin ex-trusion protein 1(MATE1) and MATE2/MATE2 K. A variety of transporter assays are available to test drugtransporter interactions, transporter-mediated drugdrug interactions, and transporter-mediated toxicity. The drug binding site of ABC transporters is accessible from the cytoplasm or the inner leaflet of the plasma membrane. Therefore, vesicular transport assays utilizing inside-out vesicles are commonly used assays, where the directionality of transport results in drugs being transported into the vesicle. Monolayer assays utilizing polarized cells expressing efflux transporters are the test systems suggested by regulatory agencies. However, in some monolayers, uptake transporters must be coexpressed with efflux transporters to assure detectable transport of low passive permeability drugs. For uptake transporters mediating cellular drug uptake, utilization of stable transfectants have been suggested. In vivo animal models complete the testing battery. Some issues, such as in vivo relevance, gender difference, age and ontogeny issues can only be addressed using in vivo models. Transporter specificity is provided by using knock-out or mutant models. Alternatively, chemical knock-outs can be employed. Compensatory changes are less likely when using chemical knockouts. On the other hand, specific inhibitors for some uptake transporters are not available, limiting the options to genetic knock-outs.展开更多
This paper collects and synthesizes the technical requirements, implementation, and validation methods for quasi-steady agent-based simulations of interconnectionscale models with particular attention to the integrati...This paper collects and synthesizes the technical requirements, implementation, and validation methods for quasi-steady agent-based simulations of interconnectionscale models with particular attention to the integration of renewable generation and controllable loads. Approaches for modeling aggregated controllable loads are presented and placed in the same control and economic modeling framework as generation resources for interconnection planning studies. Model performance is examined with system parameters that are typical for an interconnection approximately the size of the Western Electricity Coordinating Council(WECC) and a control area about 1/100 the size of the system. These results are used to demonstrate and validate the methods presented.展开更多
The contribution of the genetic make-up to an individual’s capacity has long been recognized in modern pharmacology as a crucial factor leading to therapy ineffciency and toxicity, negatively impacting the economic b...The contribution of the genetic make-up to an individual’s capacity has long been recognized in modern pharmacology as a crucial factor leading to therapy ineffciency and toxicity, negatively impacting the economic burden of healthcare and restricting the monitoring of diseases. In practical terms, and in order for drug prescription to be improved toward meeting the personalized medicine concept in drug delivery, the maximum clinical outcome for most, if not all, patients must be achieved, i.e. , pharmacotyping. Such a direction although promising and of high expectation from the society, it is however hardly to be afforded for healthcare worldwide. To overcome any existed hurdles, this means that practical clinical utility of personalized medicine decisions have to be documented and validated in the clinical setting. The latter implies for drug delivery the effcient implementation of previously gained in vivo pharmacology experience with pharmacogenomics knowledge. As an approach to work faster and in a more productive way, the elaboration of advanced physiologically based phar-macokinetics models is discussed. And in better clarifying this topic, the example of tamoxifen is thoroughly presented. Overall, pharmacotyping represents a major challenge in modern therapeutics for which pharmacologists need to work in successfully fulflling this task.展开更多
文摘交流潮流约束下的机组组合问题（AC power flow constrained unit commitment,ACUC）是一个非凸的混合整数非线性规划问题,包含大规模的离散变量,极难求解。该文建立了ACUC的分离式模型,引入部分代理割方法,提出了一种新的求解UC问题的分解式算法。并在原始部分代理割（partial surrogate cuts,PSC）法的基础上,为避免在问题规模扩大时过早陷入局部最优解,结合电力系统特征,提出了引入直流潮流相关约束的改进PSC算法,改善解的质量。通过对6节点、IEEE 39节点和118节点系统的仿真计算验证了方法的有效性和适用性,在与其他算法的对比中突显了速度和精度上的优势。
文摘In this paper,we are interested in HSS preconditioners for saddle point lin- ear systems with a nonzero(2,2)-th block.We study an approximation of the spectra of HSS preconditioned matrices and use these results to illustrate and explain the spectra obtained from numerical examples,where the previous spectral analysis of HSS precon- ditioned matrices does not cover.
基金Supported by FP7 IMI MIP-DILI:Mechanism-based integrated systems for the prediction of drug-induced liver injuryFP7 Eustroke,Health-F2-2008-202213:European Stroke Research Network+1 种基金TUDAS-1-2006-0029,OMFB-00505/2007:Development of HTS kit for analyzing transporter-drug interactions using cholesterol treated insect-cells expressing human MXR transporterGOP-1.1.1-11-2011-0017:Integrated preclinical tools for the determination and the enhancement of drug absorption
文摘The human body consists of several physiological barriers that express a number of membrane transporters. For an orally absorbed drug the intestinal, hepatic, renal and blood-brain barriers are of the greatest importance. The ATP-binding cassette(ABC) transporters that mediate cellular efflux and the solute carrier transporters that mostly mediate cellular uptake are the two superfamilies responsible for membrane transport of vast majority of drugs and drug metabolites. The total number of human transporters in the two superfamilies exceeds 400, and about 40-50 transporters have been characterized for drug transport. The latest Food and Drug Administration guidance focuses on P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide 1B1(OATP1B1), OATP1B3, organic cation transporter 2(OCT2), and organic anion transporters 1(OAT1) and OAT3. The European Medicines Agency's shortlist additionally contains the bile salt export pump, OCT1, and the multidrug and toxin extrusion transporters, multidrug and toxin ex-trusion protein 1(MATE1) and MATE2/MATE2 K. A variety of transporter assays are available to test drugtransporter interactions, transporter-mediated drugdrug interactions, and transporter-mediated toxicity. The drug binding site of ABC transporters is accessible from the cytoplasm or the inner leaflet of the plasma membrane. Therefore, vesicular transport assays utilizing inside-out vesicles are commonly used assays, where the directionality of transport results in drugs being transported into the vesicle. Monolayer assays utilizing polarized cells expressing efflux transporters are the test systems suggested by regulatory agencies. However, in some monolayers, uptake transporters must be coexpressed with efflux transporters to assure detectable transport of low passive permeability drugs. For uptake transporters mediating cellular drug uptake, utilization of stable transfectants have been suggested. In vivo animal models complete the testing battery. Some issues, such as in vivo relevance, gender difference, age and ontogeny issues can only be addressed using in vivo models. Transporter specificity is provided by using knock-out or mutant models. Alternatively, chemical knock-outs can be employed. Compensatory changes are less likely when using chemical knockouts. On the other hand, specific inhibitors for some uptake transporters are not available, limiting the options to genetic knock-outs.
文摘This paper collects and synthesizes the technical requirements, implementation, and validation methods for quasi-steady agent-based simulations of interconnectionscale models with particular attention to the integration of renewable generation and controllable loads. Approaches for modeling aggregated controllable loads are presented and placed in the same control and economic modeling framework as generation resources for interconnection planning studies. Model performance is examined with system parameters that are typical for an interconnection approximately the size of the Western Electricity Coordinating Council(WECC) and a control area about 1/100 the size of the system. These results are used to demonstrate and validate the methods presented.
文摘The contribution of the genetic make-up to an individual’s capacity has long been recognized in modern pharmacology as a crucial factor leading to therapy ineffciency and toxicity, negatively impacting the economic burden of healthcare and restricting the monitoring of diseases. In practical terms, and in order for drug prescription to be improved toward meeting the personalized medicine concept in drug delivery, the maximum clinical outcome for most, if not all, patients must be achieved, i.e. , pharmacotyping. Such a direction although promising and of high expectation from the society, it is however hardly to be afforded for healthcare worldwide. To overcome any existed hurdles, this means that practical clinical utility of personalized medicine decisions have to be documented and validated in the clinical setting. The latter implies for drug delivery the effcient implementation of previously gained in vivo pharmacology experience with pharmacogenomics knowledge. As an approach to work faster and in a more productive way, the elaboration of advanced physiologically based phar-macokinetics models is discussed. And in better clarifying this topic, the example of tamoxifen is thoroughly presented. Overall, pharmacotyping represents a major challenge in modern therapeutics for which pharmacologists need to work in successfully fulflling this task.
