Biomedical subjects

Michael R Webb

Publications and source records attributed to Michael R Webb.

5 recordsLinked to original sources

PubMed2006

Improved monochromatic imaging spectrometer.

Distortion inherent to a previously described system for acquisition of two-dimensional monochromatic spatial images is described. A solution is offered in the form of an improved instrument. The system uses a Czerny-Turner monochromator for spectral discrimination and a charge-coupled device (CCD) as the detector. A second Czerny-Turner monochromator, with identical dimensions, is added to correct the distortion, albeit with a slight loss in spatial resolution. With the earlier uncorrected arrangement, spatial resolution was on the order of 0.1 mm vertically and 0.3 mm horizontally, with a magnification of 0.52. With the same magnification, the new, corrected system offers spatial resolution of 0.1 mm vertically and 0.4 mm horizontally.

Color↗

PubMed2005

Modeling individual differences in cognition.

Many evaluations of cognitive models rely on data that have been averaged or aggregated across all experimental subjects, and so fail to consider the possibility of important individual differences between subjects. Other evaluations are done at the single-subject level, and so fail to benefit from the reduction of noise that data averaging or aggregation potentially provides. To overcome these weaknesses, we have developed a general approach to modeling individual differences using families of cognitive models in which different groups of subjects are identified as having different psychological behavior. Separate models with separate parameterizations are applied to each group of subjects, and Bayesian model selection is used to determine the appropriate number of groups. We evaluate this individual differences approach in a simulation study and show that it is superior in terms of the key modeling goals of prediction and understanding. We also provide two practical demonstrations of the approach, one using the ALCOVE model of category learning with data from four previously analyzed category learning experiments, the other using multidimensional scaling representational models with previously analyzed similarity data for colors. In both demonstrations, meaningful individual differences are found and the psychological models are able to account for this variation through interpretable differences in parameterization. The results highlight the potential of extending cognitive models to consider individual differences.

Cognition↗

PubMed2004

Comparative analysis of topoisomerase IB inhibition and DNA intercalation by flavonoids and similar compounds: structural determinates of activity.

Flavonoids and other polyphenolic compounds have been shown to inhibit human topoisomerase IB (topo I) through both inhibition of relaxation activity and through stabilization of the cleavable complex (poisoning). Some flavonoids have also been shown to intercalate DNA, and an association of topoisomerase inhibition with intercalation has been noted. We surveyed 34 polyphenolic compounds, primarily flavonoid glycones and aglycones, for their ability to inhibit topo I and to intercalate DNA using an in vitro gel electrophoresis method. We show that the most potent topo I poisons are the flavones and flavonols, and that these generally, but not always, are found to be DNA intercalators. There was no clear correlation, however, of topo-I-poisoning activity with the degree of DNA unwinding. Surprisingly, both DNA intercalation and topo I poisoning were shown to occur with some flavone glycones, including the C-glycosylflavone orientin. Inhibition of relaxation activity by flavonoids was found to be difficult to quantify and was most likely to be due to non-specific inhibition through flavonoid aggregation. As part of a structure-activity analysis, we also investigated the acid-base chemistry of flavonoids and determined that many flavonoids show acid-base activity with a pK(a) in the physiological pH region. For this reason, subtle pH changes can have significant effects on solution activity of flavonoids and their concomitant biological activity. In addition, these effects may be complicated by pH-dependent aggregation and oxidative degradation. Finally, we develop a simple model for the intercalation of flavonoids into DNA and discuss possible consequences of intercalation and topoisomerase inhibition on a number of cellular processes.

Animals↗

PubMed2003

A gel electrophoresis assay for the simultaneous determination of topoisomerase I inhibition and DNA intercalation.

The DNA maintenance enzyme, topoisomerase I, is thought to play crucial roles in all living cells and for this reason inhibitors of this enzyme have been much studied. In this paper we describe a gel electrophoresis method capable of characterizing and quantifying inhibition of topoisomerase I by selected compounds. Inhibitors of topoisomerase I are often associated with intercalative binding to DNA and the method can simultaneously determine intercalative binding (as DNA unwinding) except in the cases where inhibition is prohibitively strong. The method uses closed circular (plasmid) DNA and can separate single-strand nicked, linearized (double-strand nicked), fully relaxed, partially relaxed (topoisomers), and supercoiled forms of the plasmid so that topoisomerase-dependent DNA cleavage (poisoning) can also be determined. By quantifying poisoning, inhibition, and intercalation simultaneously and separately in relation to reference compounds it is possible to make quantitative determinations of these phenomena for comparative purposes. Data for the topoisomerase I inhibitor, luteolin, are presented.

Camptothecin↗

PubMed2002

Dietary catechin delays tumor onset in a transgenic mouse model.

BACKGROUND: Evidence exists that red wine, which contains a large array of polyphenols, is protective against cardiovascular disease and possibly cancer. OBJECTIVE: We tested the hypothesis that catechin, the major monomeric polyphenol in red wine, can delay tumor onset in transgenic mice that spontaneously develop tumors. DESIGN: Mice were fed a nutritionally complete amino acid-based diet supplemented with (+)-catechin (0-8 mmol/kg diet) or alcohol-free solids from red wine. Mice were examined daily; the age at which a first tumor appeared was recorded as the age at tumor onset. Plasma catechin and metabolite concentrations were quantified at the end of the study. RESULTS: Dietary catechin significantly delayed tumor onset; a positive, linear relation was observed between the age at tumor onset and either the amount of dietary catechin (r(2) = 0.761, P < 0.001) or plasma catechin and metabolite concentrations (r(2) = 0.408, P = 0.003). No significant effects on tumor onset were observed when mice consumed a diet supplemented with wine solids containing <0.22 mmol catechin/kg diet, whereas a previous study showed that wine solids with a similar total polyphenol concentration but containing approximately 4 times more catechin significantly delayed tumor onset by approximately 30 d compared with a control diet. The catechin composition of the wines is directly related to processing conditions during vinification. CONCLUSIONS: Physiologic intakes of specific dietary polyphenols, such as catechin, may play an important role in cancer chemoprevention. Wines have different polyphenol concentrations and compositions; therefore, the overall health benefits of individual wines differ.

Aging↗