Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery an...Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.展开更多
A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminat...A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminate signal from background events.Signal detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of two.With the addition of the Phase II dataset taken with an upgraded detector,the median 90%confidence level half-life sensitivity of 2νββdecay to the 0+1 state of 136Ba is 2.9×10^(24)yr using a total^(136)Xe exposure of 234.1 kg yr.No statistically significant evidence for 2νββdecay to the 0^(+)_(1)state is observed,leading to a lower limit of T2ν1/2(0^(+)→0^(+)_(1))>1.4×10^(24)yr at 90%confidence level,improved by 70%relative to the current world's best constraint.展开更多
1 Results In persuit of better safety controls of lithium batteries,much efforts has been focused on the development of the internal and self-actuating overcharge protection additives.We report a novel electropolymeri...1 Results In persuit of better safety controls of lithium batteries,much efforts has been focused on the development of the internal and self-actuating overcharge protection additives.We report a novel electropolymerizable electrolyte additive for overcharge protection of lithium batteries. Electrochemical properties and overcharge behavior of NPM as a new polymerizable electrolyte additive for overcharge protection of lithium ion batteries are studied by cyclic voltammetry,charge-discharge measurements...展开更多
1 Results In order to overcome the inherent incompatibility of PC with graphite in the lithium ion battery system, improve their electrochemical performance at low temperature,phenyl tris-2-methoxydiethoxy silane (PTM...1 Results In order to overcome the inherent incompatibility of PC with graphite in the lithium ion battery system, improve their electrochemical performance at low temperature,phenyl tris-2-methoxydiethoxy silane (PTMS) has been studied as an additive to the PC-based electrolyte of lithium ion batteries with graphite anode. From the cyclic voltammogram for the graphite anode in the PC-based electrolyte,we find that in the case of the electrolyte without the additive,there is a large irreversible peak ne...展开更多
基金supported in part by grants from the National Institutes of Health (CA023074,CA092596,ES004940,ES006694,and ES020867,USA)。
文摘Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.
文摘A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminate signal from background events.Signal detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of two.With the addition of the Phase II dataset taken with an upgraded detector,the median 90%confidence level half-life sensitivity of 2νββdecay to the 0+1 state of 136Ba is 2.9×10^(24)yr using a total^(136)Xe exposure of 234.1 kg yr.No statistically significant evidence for 2νββdecay to the 0^(+)_(1)state is observed,leading to a lower limit of T2ν1/2(0^(+)→0^(+)_(1))>1.4×10^(24)yr at 90%confidence level,improved by 70%relative to the current world's best constraint.
文摘1 Results In persuit of better safety controls of lithium batteries,much efforts has been focused on the development of the internal and self-actuating overcharge protection additives.We report a novel electropolymerizable electrolyte additive for overcharge protection of lithium batteries. Electrochemical properties and overcharge behavior of NPM as a new polymerizable electrolyte additive for overcharge protection of lithium ion batteries are studied by cyclic voltammetry,charge-discharge measurements...
文摘1 Results In order to overcome the inherent incompatibility of PC with graphite in the lithium ion battery system, improve their electrochemical performance at low temperature,phenyl tris-2-methoxydiethoxy silane (PTMS) has been studied as an additive to the PC-based electrolyte of lithium ion batteries with graphite anode. From the cyclic voltammogram for the graphite anode in the PC-based electrolyte,we find that in the case of the electrolyte without the additive,there is a large irreversible peak ne...
