Design principles of semantic binary database management systems

The Semantic Binary Data Model (SBM) is a viable alternative to the now-dominant relational data model. SBM would be especially advantageous for applications dealing with complex interrelated networks of objects provided that a robust efficient implementation can be achieved. This dissertation presents an implementation design method for SBM, algorithms, and their analytical and empirical evaluation. Our method allows building a robust and flexible database engine with a wider applicability range and improved performance. ^ Extensions to SBM are introduced and an implementation of these extensions is proposed that allows the database engine to efficiently support applications with a predefined set of queries. A New Record data structure is proposed. Trade-offs of employing Fact, Record and Bitmap Data structures for storing information in a semantic database are analyzed. ^ A clustering ID distribution algorithm and an efficient algorithm for object ID encoding are proposed. Mapping to an XML data model is analyzed and a new XML-based XSDL language facilitating interoperability of the system is defined. Solutions to issues associated with making the database engine multi-platform are presented. An improvement to the atomic update algorithm suitable for certain scenarios of database recovery is proposed. ^ Specific guidelines are devised for implementing a robust and well-performing database engine based on the extended Semantic Data Model. ^

Sustaining culture through architecture : how can local, vernacular architectural principles be adapted to contemporary design in a village in Guyana

This thesis explores how architecture can adapt local vernacular design principles to contemporary building design in a rural setting. Vernacular buildings in Guyana present a unique and coherent set of design principles developed in response to climatic and cultural conditions. The concept of “habitus” proposed by philosopher Pierre Bourdieu describing the evolving nature of social culture was used to interpret Guyanese local buildings. These principles were then applied to the design of a Women’s Center in the village of Port Mourant on the east coast of Guyana. The design specifically interpreted the “bottom-house” of local Guyanese architecture, an inherently flexible transitional outdoor space beneath raised buildings. The design of the Women’s Center demonstrates how contemporary architectural design can respond to climatic requirements, local preferences and societal needs to support the local culture.

Design and Synthesis of 4-N-Alkanoyl and 4-N-Alkyl Gemcitabine Analogues Suitable for Positron Emission Tomography

Gemcitabine is a highly potent chemotherapeutic nucleoside agent used in the treatment of several cancers and solid tumors. However, it is therapeutically limitated because of toxicity to normal cells and its rapid intracellular deamination by cytidine deaminase into the inactive uracil derivative. Modification at the 4-(N) position of gemcitabine's exocyclic amine to an -amide functionality is a well reported prodrug strategy which has been that confers a resistance to intracellular deamination while also altering pharmacokinetics of the parent drug. Coupling of gemcitabine to carboxylic acids with varying terminal moieties afforded the 4-N-alkanoylgemcitabines whereas reaction of 4-N-tosylgemcitabine with the corresponding alkyl amines gave the 4-N-alkylgemcitabines. The 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues with a terminal hydroxyl group on the 4-N-alkanoyl or 4-N-alkyl chain were efficiently fluorinated either with diethylaminosulfur trifluoride or under conditions that are compatible with the synthetic protocols for 18F labeling, such as displacement of the corresponding mesylate with KF/Kryptofix 2.2.2. The 4-N-alkanoylgemcitabine analogues displayed potent cytostatic activities against murine and human tumor cell lines with 50% inhibitory concentration (IC50) values in the range of low nM, whereas cytotoxicity of the 4-N-alkylgemcitabine derivatives were in the low to modest µM range. The cytostatic activity of the 4-N-alkanoylgemcitabines was reduced by several orders of magnitude in the 2'-deoxycytidine kinase (dCK)-deficient CEM/dCK- cell line while the 4-N-alkylgemcitabines were only lowered by 2-5 times. None of the 4-N-modified gemcitabines were found to be substrates for cytosolic dCK, however all were found to inhibit DNA synthesis. As such, the 4-N-alkanoyl gemcitabine derivatives likely need to be converted to gemcitabine prior to achieving their significant cytostatic potential, whereas the 4-N-alkylgemcitabines reach their modest activity without "measurable" conversion to gemcitabine. Thus, the 4-N-alkylgemcitabines provide valuable insight on the metabolism of 4-N-modified gemcitabine prodrugs.