Neural-network-based classification of cognitively normal, demented, Alzheimer disease and vascular dementia from single photon emission with computed tomography image data from brain.

Single photon emission with computed tomography (SPECT) hexamethylphenylethyleneamineoxime technetium-99 images were analyzed by an optimal interpolative neural network (OINN) algorithm to determine whether the network could discriminate among clinically diagnosed groups of elderly normal, Alzheimer disease (AD), and vascular dementia (VD) subjects. After initial image preprocessing and registration, image features were obtained that were representative of the mean regional tissue uptake. These features were extracted from a given image by averaging the intensities over various regions defined by suitable masks. After training, the network classified independent trials of patients whose clinical diagnoses conformed to published criteria for probable AD or probable/possible VD. For the SPECT data used in the current tests, the OINN agreement was 80 and 86% for probable AD and probable/possible VD, respectively. These results suggest that artificial neural network methods offer potential in diagnoses from brain images and possibly in other areas of scientific research where complex patterns of data may have scientifically meaningful groupings that are not easily identifiable by the researcher.

Maintenance of Epstein–Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1

EBV-encoded nuclear antigen-1 (EBNA-1) binding to a cis-acting viral DNA element, oriP, enables plasmids to persist in dividing human cells as multicopy episomes that attach to chromosomes during mitosis. In investigating the significance of EBNA-1 binding to mitotic chromosomes, we identified the basic domains of EBNA-1 within amino acids 1–89 and 323–386 as critical for chromosome binding. In contrast, the EBNA-1 C terminus (amino acids 379–641), which includes the nuclear localization signal and DNA-binding domain, does not associate with mitotic chromosomes or retain oriP plasmid DNA in dividing cell nuclei, but does enable the accumulation of replicated oriP-containing plasmid DNA in transient replication assays. The importance of chromosome association in episome maintenance was evaluated by replacing EBNA-1 amino acids 1–378 with cell proteins that have similar chromosome binding characteristics. High-mobility group-I amino acids 1–90 or histone H1–2 could substitute for EBNA-1 amino acids 1–378 in mediating more efficient accumulation of replicated oriP plasmid, association with mitotic chromosomes, nuclear retention, and long-term episome persistence. These data strongly support the hypothesis that mitotic chromosome association is a critical factor for episome maintenance. The replacement of 60% of EBNA-1 with cell protein is a significant step toward eliminating the need for noncellular protein sequences in the maintenance of episomal DNA in human cells.