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Biomedical subjects

Glen Nuckolls

Publications and source records attributed to Glen Nuckolls.

2 recordsLinked to original sources

On optimizing distance-based similarity search for biological databases.

Similarity search leveraging distance-based index structures is increasingly being used for both multimedia and biological database applications. We consider distance-based indexing for three important biological data types, protein k-mers with the metric PAM model, DNA k-mers with Hamming distance and peptide fragmentation spectra with a pseudo-metric derived from cosine distance. To date, the primary driver of this research has been multimedia applications, where similarity functions are often Euclidean norms on high dimensional feature vectors. We develop results showing that the character of these biological workloads is different from multimedia workloads. In particular, they are not intrinsically very high dimensional, and deserving different optimization heuristics. Based on MVP-trees, we develop a pivot selection heuristic seeking centers and show it outperforms the most widely used corner seeking heuristic. Similarly, we develop a data partitioning approach sensitive to the actual data distribution in lieu of median splits.

Algorithms↗

The life cycle of chondrocytes in the developing skeleton.

Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation, differentiation and apoptosis. Transduction of these signals within the developing mesenchymal cells and chondrocytes results in changes in gene expression mediated by transcription factors including Smads, Msx2, Sox9, signal transducer and activator of transcription (STAT), and core-binding factor alpha 1. Further investigation of the interactions of these signaling pathways will contribute to an understanding of cartilage growth and development, and will allow for the development of strategies for the early detection, prevention and treatment of diseases and disorders affecting the skeleton.

Bone Development↗