2 research outputs found
Some Problems and Solutions in the Experimental Science of Technology: The Proper Use and Reporting of Statistics in Computational Intelligence, with an Experimental Design from Computational Ethnomusicology
Statistics is the meta-science that lends validity and credibility to The Scientific Method. However, as a complex and advanced Science in itself, Statistics is often misunderstood and misused by scientists, engineers, medical and legal professionals and others. In the area of Computational Intelligence (CI), there have been numerous misuses of statistical techniques leading to the publishing of insupportable results, which, in addition to being a problem in itself, has also contributed to a degree of rift between the Statistics/Statistical Learning community and the Machine Learning/Computational Intelligence community. This talk surveys a number of misuses of statistical inference in CI settings, including well-known and more rarely discussed examples. These are followed by an overview of concepts and techniques that are central to model evaluation. Finally, an experimental design is presented for a statistically valid comparison of multiple hypotheses for a particular real-world problem combining Information Theory, Neural Networks, Statistics, and Computational Ethnomusicology.https://pdxscholar.library.pdx.edu/systems_science_seminar_series/1060/thumbnail.jp
Development and Validation of the First Assay Method Coupling Liquid Chromatography with Chemiluminescence for the Simultaneous Determination of Menadione and Its Thioether Conjugates in Rat Plasma
Menadione
(2-methyl-1,4-naphthoquinone, MQ), a component of multivitamin
drugs with antihemorrhagic, antineoplastic, and antimalarial activity,
is frequently used to investigate quinone-induced cytotoxicity. The
formation of MQ conjugates with glutathione (GSH) by Michael addition
and subsequent biotransformation to yield <i>N</i>-acetyl-l-cysteine conjugates is believed to be an important detoxification
process. However, the resulting conjugates, 2-methyl-3-(glutathione-<i>S</i>-yl)-1,4-naphthoquinone (MQ-GS) and 2-methyl-3-(<i>N</i>-acetyl-l-cysteine-<i>S</i>-yl)-1,4-naphthoquinone
(MQ-NAC), retain the ability to redox cycle and to arylate cellular
nucleophiles. Although the nephrotoxicity and hepatotoxicity of MQ-thiol
conjugates have been reported <i>in vitro</i>, methods for
their determination <i>in vivo</i> have yet to be published.
Herein, a highly sensitive, simple, and selective HPLC-chemiluminescence
(HPLC-CL) coupled method is reported, allowing for the first time
the simultaneous determination of MQ, MQ-GS, and MQ-NAC in rat plasma
after MQ administration. Our method exploits the unique redox characteristics
of MQ, MQ-GS, and MQ-NAC to react with dithiothreitol (DTT) to liberate
reactive oxygen species (ROS) which are detected by a CL assay using
luminol as a CL probe. To verify the proposed mechanism, MQ-GS and
MQ-NAC were synthetically prepared. Specimen preparation involved
solid-phase extraction on an Oasis HLB cartridge followed by isocratic
elution on an ODS column. No interference from endogenous substances
was detected. Linearity was observed in the range of 5–120
nM for MQ-GS and MQ-NAC and 10–240 nM for MQ, with detection
limits (S/N of 3) of 1.4, 0.8, and 128 fmol for MQ-GS, MQ-NAC, and
MQ, respectively. The application of our method reported here is the
first to extensively study the stability and reversibility of thiol-quinones