Altered white matter integrity in temporal lobe epilepsy: association with cognitive and clinical profiles.

PURPOSE: Diffusion tensor imaging (DTI) studies have reported substantial white matter abnormalities in patients with temporal lobe epilepsy (TLE). However, limited data exist regarding the extent of white matter tract abnormalities, cognitive effects of these abnormalities, and relationship to clinical factors. The current study examined these issues in subjects with chronic TLE. METHODS: DTI data were obtained in 12 TLE subjects and 10 age-matched healthy controls. Voxel-wise statistical analysis of fractional anisotropy (FA) was carried out using tract-based spatial statistics (TBSS). White matter integrity was correlated with cognitive performance and epilepsy-related clinical parameters. RESULTS: Subjects with TLE, as compared to healthy controls, demonstrated four clusters of reduced FA, in anterior temporal lobe, mesial temporal lobe, and cerebellum ipsilateral, as well as frontoparietal lobe contralateral to the side of seizure onset. Mean FA was positively correlated with delayed memory, in anterior temporal lobe; and immediate memory, in mesial temporal lobe. Lower FA values in the posterior region of corpus callosum were related to earlier age of seizure onset. CONCLUSION: TLE is associated with widespread disturbances in white matter tracts and these changes have important cognitive and clinical consequences.

Generalized gene adjacencies, graph bandwidth, and clusters in yeast evolution.

We present a parameterized definition of gene clusters that allows us to control the emphasis placed on conserved order within a cluster. Though motivated by biological rather than mathematical considerations, this parameter turns out to be closely related to the bandwidth parameter of a graph. Our focus will be on how this parameter affects the characteristics of clusters: how numerous they are, how large they are, how rearranged they are, and to what extent they are preserved from ancestor to descendant in a phylogenetic tree. We infer the latter property by dynamic programming optimization of the presence of individual edges at the ancestral nodes of the phylogeny. We apply our analysis to a set of genomes drawn from the Yeast Gene Order Browser.

On updating torsion angles of molecular conformations.

A conformation of a molecule is defined by the relative positions of atoms and by the chirality of asymmetric atoms in the molecule. The three main representations for conformations of molecules are Cartesian coordinates, a distance geometry descriptor (which consists of a distance matrix and the signs of the volumes of quadruples of atoms), and internal coordinates. In biochemistry, conformational changes of a molecule are usually described in terms of internal coordinates. However, for many applications, such as molecular docking, the Cartesian coordinates of atoms are needed for computation. Although, for each conformational change, the Cartesian coordinates of atoms can be updated in linear time (which is optimal asymptotically), the constant factor becomes significant if a large number of updates are needed. Zhang and Kavraki (J. Chem. Inf. Comput. Sci. 2002, 42, 64-70) examined three methods: the simple rotations, the Denavit-Hartenberg local frames, and the atom-group local frames. On the basis of their implementations, they showed that the atom-group local frames are more efficient than the other two. In this paper, by expressing the torsion-angle change as a composition of translations and rotations, we observe that the simple rotations can be implemented in an efficient way by taking advantage of consecutive operations. Both quantitative and experimental comparisons show that the improved simple rotations, in which rotations are expressed in unit quaternions, are as efficient as the atom-group local frames and, thus, have the advantage of avoiding the need of precomputations of a set of local frames and transformations between them.

Yucca: an efficient algorithm for small-molecule docking.

In this paper, we present a new algorithm, which is based on an efficient heuristic for local search, for rigid protein-small-molecule docking. We tested our algorithm, called Yucca, on the recent 100-complex benchmark, using the conformer generator OMEGA to generate a set of low-energy conformers. The results showed that Yucca is competitive both in terms of algorithm efficiency and docking accuracy.

Barnacle: an assembly algorithm for clone-based sequences of whole genomes.

We propose an assembly algorithm Barnacle for sequences generated by the clone-based approach. We illustrate our approach by assembling the human genome. Our novel method abandons the original physical-mapping-first framework. As we show, Barnacle more effectively resolves conflicts due to repeated sequences which is the main difficulty of the sequence assembly problem. In addition, we are able to detect inconsistencies in the underlying data. We present and compare our results on the December 2001 freeze of the public working draft of the human genome with NCBI's assembly (Build 28). The assembly of December 2001 freeze of the public working draft generated by Barnacle and the source code of Barnacle are available at (http://www.cs.rutgers.edu/~vchoi).