Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydrolyzed metabolites of prilocaine (o-toluidine) and lidocaine (2,6-xylidine) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized. In the present study, we aimed to identify the human enzym...

Gene-environment interaction (GEI) analysis can potentially enhance gene discovery for common complex traits. However, genome-wide interaction analysis is computationally intensive. Moreover, analysis of longitudinal data in families is much more challenging due to the two sources of correlations arising from longitudinal measurements and family relationships. GWIS of longitudinal family data c...

The development of model-based methods for incomplete data has been a seminal contribution to statistical practice. Under the assumption of ignorable missingness, one estimates the joint distribution of the complete data for thetainTheta from the incomplete or observed data y(obs). Many interesting models involve one-to-one transformations of theta. For example, with y(i) approximately N(mu, Si...

A fundamental challenge to understanding patterns in ecological systems lies in employing methods that can analyse, test and draw inference from measured associations between variables across scales. Hierarchical linear models (HLM) use advanced estimation algorithms to measure regression relationships and variance-covariance parameters in hierarchically structured data. Although hierarchical m...

The ability of a drug to cause clinically significant drug-drug interactions due to direct or metabolism-dependent inhibition of cytochrome P450 (CYP) can generally be predicted from in vitro studies with human liver microsomes (HLM) or recombinant CYP enzymes, as recommended by the FDA and other regulatory agencies. This review highlights some examples of system-dependent inhibition of CYP and...

The aim of this study is to investigate the metabolic (cytochrome P450-dependent) behaviour of pyrazolo[3,4-d]pyrimidines 1-10 dual Abl/Src kinase inhibitors. All the compounds demonstrate good metabolic stability both in human liver (HLM) and in rat liver (RLM) microsomes. Moreover, all the tested molecules undergo the same metabolic CYP-dependent reactions, namely oxidative dechlorination and...

Focusing on the problem of low computation efficiency in the process of tracking human 3D motion, an algorithm for Estimating 3D arm motion with Hierarchy Limb Model (HLM) is proposed. In our algorithm, the Hierarchy Limb Model (HLM) is proposed based on the human 3D skeleton model. Facilitated by graph decomposition, the arm motion state space, modeled by Hierarchy Limb Model (HLM), can be dis...

The metabolism of the carcinogenic mycotoxin aflatoxin B1 (AFB1) was examined in microsomes derived from human lymphoblastoid cell lines expressing transfected CYP1A2 or CYP3A4 complementary DNAs and in microsomes prepared from human liver donors (n = 4). Lymphoblast microsomes expressing only CYP1A2 activated AFB1 to AFB1-8,9-epoxide (AFB1-8,9-epoxide trapped as the glutathione, conjugate) at ...