James Gigrich is a PhD candidate at George Washington University. He has an MS in Operation Research from Georgia Institute of Technology and a BS in Electrical Engineering from West Point. He currently is the Senior Director of Government Relations and National Security Programs for Keysight Technologies, the legacy Hewlett-Packard Company and a world leader in measurement technologies.
Systems engineering recognizes that each system is an integrated whole, even though composed of diverse specialized structures and sub-functions. Hepatocytes are complex cells with numerous subsystems, and the interactions among hepatocytes are complex and not completely understood. Systems engineering looks at systems of all types and emphasizes the relationships and interactions between components. Systems engineering can analyze living systems in terms of design, information processing, optimization, and other explicit concepts, by using various quantitative System Engineering tools that include data analysis, modeling and simulation, signaling processing and graph theory. The application of these tools provides new insight into the intricate workings of hepatocytes. Hepatocytes are complex and yet exceedingly connected systems that make it tremendously challenging to understand the underlying signaling pathways and interpreting numerous and varied high dimensional measurement data. Currently, there is a paradigm shift from apical endpoints in animal testing to perturbation of toxicity pathways in human hepatocyte cells. Gene expression data of PPARα binding measured over multiple concentrations and times of GW7647 doses along with downstream phenotypes were examined using multivariate data analysis. Associated phenotype changes to hepatocytes showed a correlation with high-dimensional multivariate genomic data – gene expression profiling data. The use of multivariate techniques like principal components analysis, factor analysis, and cluster analysis to analyze gene expression and phenotype data allows for more informed decision-making in toxicity testing.
Background: 2-Oxoglutarate and ferrous iron dependent oxygenases are involved in a variety of biological processes in aerobic organisms ranging from humans to bacteria. Synthetic N-oxalylglycine has been identified as a broad-spectrum 2OG oxygenase inhibitor. We report the identification of NOG as a natural product present in spinach leaves. Method: To investigate whether NOG and related derivatives naturally occur in spinach leaves, we first developed an analytical method using reversed-phase liquid chromatography mass spectrometry (RP-LC/MS) and an NOG standard. The detection of NOG provided a linear response with concentration in the range 10–1000 µM with a correlation coefficient R²>0.998. The detection limits for NOG were 5 μM and the limit of quantification was13 μM. Results: The LC-MS, LC-MS/MS, NMR, and ESI accurate mass analyses provide positive evidence for the presence of NOG in spinach leaves. The amount of NOG at natural abundance in the spinach leaves sample was calculated to be 0.1681 mg per 3g dry weight of spinach leaves. Conclusions: The results presented here demonstrate that NOG is present as natural products in plant tissues known to contain high levels of oxalic acid, i.e. spinach. We did not detect NOG in E. coli, or human tissue culture cells. Thus, whilst we cannot rule out the possibility that NOG is present in animal cells, there is no evidence for its presence at currently detectable levels. Whether or not the amount of NOG present in spinach leaves is bioavailable in sufficient quantity to elicit a physiological effect upon ingestion remains to be investigated.