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Gene expression profiles are an increasingly common data source that can yield insights into the functions of cells at a system-wide level. The present work considers the limitations in information content of gene expression data for reverse engineering regulatory networks. An in silico genetic regulatory network was constructed for this purpose. Using the(More)
We have developed a bioinformatics tool named PAINT that automates the promoter analysis of a given set of genes for the presence of transcription factor binding sites. Based on coincidence of regulatory sites, this tool produces an interaction matrix that represents a candidate transcriptional regulatory network. This tool currently consists of (1) a(More)
A model genetic regulatory network for the evaluation of genetic regulatory network identification methods is described in the present work. This model is novel because of its mechanistic basis and its relatively large (10 gene) scale. The model is used to evaluate several simple techniques from the literature for identifying genetic regulatory networks(More)
The broad conceptual postulate that systems engineering techniques developed for complex chemical processes may be applicable to complex cell biological processes is very compelling. However, a naïve, "direct" application of systems engineering techniques to biological problems of practical significance may be rendered virtually ineffective by fundamental(More)
Although the myelin membrane contains only a small set of major proteins, more sensitive assays indicate the presence of a plethora of uncharacterized proteins. We have used an antibody perturbation approach to reversibly block the differentiation of prooligodendroblasts into myelinating cells, and, in combination with a differential screening procedure,(More)
Most partition-based cluster analysis methods (e.g., k-means) will partition any dataset D into k subsets, regardless of the inherent appropriateness of such a partitioning. This paper presents a family of permutation-based procedures to determine both the number of clusters k best supported by the available data and the weight of evidence in support of(More)
Chronic alcohol use changes the brain’s inflammatory state. However, there is little work examining the progression of the cytokine response during alcohol withdrawal, a period of profound autonomic and emotional upset. This study examines the inflammatory response in the central nucleus of the amygdala (CeA) and dorsal vagal complex (DVC), brain regions(More)
Parkinson's disease and its characteristic symptoms are thought to arise from the progressive degeneration of specific midbrain dopamine (DA) neurons. In humans, DA neurons of the substantia nigra (SN) and their projections to the striatum show selective vulnerability, while neighboring DA neurons of the ventral tegmental area (VTA) are relatively spared(More)
Several late stages of the oligodendrocyte (OL) developmental lineage can be identified immunologically in the newborn rat brain. However, OL lineage-specific markers are not available for the detection of the less mature, yet determined, OL precursors. We have developed a retrospective bioassay, combining limiting dilution analysis with a novel culture(More)
One objective of systems biology is to create predictive, quantitative models of the transcriptional regulation networks that govern numerous cellular processes. Gene expression measurements, as provided by microarrays, are commonly used in studies that attempt to infer the regulation underlying these processes. At present, most gene expression models that(More)