DESIGN AND IMPLEMENTATION OF THE INSTRUCTION SET ARCHITECTURE FOR DATA LARS

The ideal memory system assumed by most programmers is one which has high capacity, yet allows any word to be accessed instantaneously. To make the hardware approximate this performance, an increasingly complex memory hierarchy, using caches and techniques like automatic prefetch, has evolved. However, as the gap between processor and memory speeds continues to widen, these programmer-visible mechanisms are becoming inadequate. Part of the recent increase in processor performance has been due to the introduction of programmer/compiler-visible SWAR (SIMD Within A Register) parallel processing on increasingly wide DATA LARs (Line Associative Registers) as a way to both improve data access speed and increase efficiency of SWAR processing. Although the base concept of DATA LARs predates this thesis, this thesis presents the first instruction set architecture specification complete enough to allow construction of a detailed prototype hardware design. This design was implemented and tested using a hardware simulator

A Plausible Role for the Presence of Internal Shine-Dalgarno Sites

The presence of nucleotide hybridization between the 3′ end of 16S rRNA and mRNA sequence upstream of the start codon is well known in bacteria. In this paper, we detect the presence of such hybridization sites inside the coding regions of E. coli genes, and analyze their proximity to clusters of slow-translating codons. We study this phenomenon in genes of high and low expression separately. Based on our findings, we propose an explanation for the presence of RNA hybridization within the translated regions of bacterial genes

Analysis of Free Energy Signals Arising from Nucleotide Hybridization Between rRNA and mRNA Sequences during Translation in Eubacteria

A decoding algorithm is tested that mechanistically models the progressive alignments that arise as the mRNA moves past the rRNA tail during translation elongation. Each of these alignments provides an opportunity for hybridization between the single-stranded, 3′-terminal nucleotides of the 16S rRNA and the spatially accessible window of mRNA sequence, from which a free energy value can be calculated. Using this algorithm we show that a periodic, energetic pattern of frequency 1/3 is revealed. This periodic signal exists in the majority of coding regions of eubacterial genes, but not in the non-coding regions encoding the 16S and 23S rRNAs. Signal analysis reveals that the population of coding regions of each bacterial species has a mean phase that is correlated in a statistically significant way with species (G + C) content. These results suggest that the periodic signal could function as a synchronization signal for the maintenance of reading frame and that codon usage provides a mechanism for manipulation of signal phase

Multipattern Consensus Regions in Multiple Aligned Protein Sequences and Their Segmentation

<p/> <p>Decomposing a biological sequence into its functional regions is an important prerequisite to understand the molecule. Using the multiple alignments of the sequences, we evaluate a segmentation based on the type of statistical variation pattern from each of the aligned sites. To describe such a more general pattern, we introduce multipattern consensus regions as segmented regions based on conserved as well as interdependent patterns. Thus the proposed consensus region considers patterns that are statistically significant and extends a local neighborhood. To show its relevance in protein sequence analysis, a cancer suppressor gene called p53 is examined. The results show significant associations between the detected regions and tendency of mutations, location on the 3D structure, and cancer hereditable factors that can be inferred from human twin studies.</p

Analysis of Ultra Low Genome Conservation in Clostridium difficile

Microarray-based comparative genome hybridisations (CGH) and genome sequencing of Clostridium difficile isolates have shown that the genomes of this species are highly variable. To further characterize their genome variation, we employed integration of data from CGH, genome sequencing and putative cellular pathways. Transcontinental strain comparison using CGH data confirmed the emergence of a human-specific hypervirulent cluster. However, there was no correlation between total toxin production and hypervirulent phenotype, indicating the possibility of involvement of additional factors towards hypervirulence. Calculation of C. difficile core and pan genome size using CGH and sequence data estimated that the core genome is composed of 947 to 1,033 genes and a pan genome comprised of 9,640 genes. The reconstruction, annotation and analysis of cellular pathways revealed highly conserved pathways despite large genome variation. However, few pathways such as tetrahydrofolate biosynthesis were found to be variable and could be contributing to adaptation towards virulence such as antibiotic resistance

Cytotoxicity of aporphines in human colon cancer cell lines HCT-116 and Caco-2: An SAR study

A series of synthetic aporphine derivatives structurally related to domesticine and nantenine (ring A, N6 and ring C truncated analogs), was evaluated in MTS cytotoxicity assays against the human colon cancer cell lines, HCT-116 and Caco-2. In general, the C1 position of ring A is tolerant of alkoxy substituents as well as a benzoyl ester functionality. Other modifications evaluated resulted in a decrease in cytotoxic activity. The most potent compounds identified had IC50 values in the range 23–38 μM, comparable to the known cytotoxic agent, etoposide

Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for 89Zr4+; however, accumulation of 89Zr in the bones of mice suggests that 89Zr4+ is released from DFO in vivo. An improved chelator for 89Zr4+ could eliminate the release of osteophilic 89Zr4+ and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of 89Zr-HOPO matched or surpassed that of 89Zr-DFO in every experiment. In healthy mice, 89Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents