Critical evaluation of diameter increment modelling in the Great Lakes region

Simulations of forest stand dynamics in a modelling framework including Forest Vegetation Simulator (FVS) are diameter driven, thus the diameter or basal area increment model needs a special attention. This dissertation critically evaluates diameter or basal area increment models and modelling approaches in the context of the Great Lakes region of the United States and Canada. A set of related studies are presented that critically evaluate the sub-model for change in individual tree basal diameter used in the Forest Vegetation Simulator (FVS), a dominant forestry model in the Great Lakes region. Various historical implementations of the STEMS (Stand and Tree Evaluation and Modeling System) family of diameter increment models, including the current public release of the Lake States variant of FVS (LS-FVS), were tested for the 30 most common tree species using data from the Michigan Forest Inventory and Analysis (FIA) program. The results showed that current public release of the LS-FVS diameter increment model over-predicts 10-year diameter increment by 17% on average. Also the study affirms that a simple adjustment factor as a function of a single predictor, dbh (diameter at breast height) used in the past versions, provides an inadequate correction of model prediction bias. In order to re-engineer the basal diameter increment model, the historical, conceptual and philosophical differences among the individual tree increment model families and their modelling approaches were analyzed and discussed. Two underlying conceptual approaches toward diameter or basal area increment modelling have been often used: the potential-modifier (POTMOD) and composite (COMP) approaches, which are exemplified by the STEMS/TWIGS and Prognosis models, respectively. It is argued that both approaches essentially use a similar base function and neither is conceptually different from a biological perspective, even though they look different in their model forms. No matter what modelling approach is used, the base function is the foundation of an increment model. Two base functions – gamma and Box-Lucas – were identified as candidate base functions for forestry applications. The results of a comparative analysis of empirical fits showed that quality of fit is essentially similar, and both are sufficiently detailed and flexible for forestry applications. The choice of either base function in order to model diameter or basal area increment is dependent upon personal preference; however, the gamma base function may be preferred over the Box-Lucas, as it fits the periodic increment data in both a linear and nonlinear composite model form. Finally, the utility of site index as a predictor variable has been criticized, as it has been widely used in models for complex, mixed species forest stands though not well suited for this purpose. An alternative to site index in an increment model was explored, using site index and a combination of climate variables and Forest Ecosystem Classification (FEC) ecosites and data from the Province of Ontario, Canada. The results showed that a combination of climate and FEC ecosites variables can replace site index in the diameter increment model.

DESIGN AND SYNTHESIS OF MULTIFUNCTIONAL POLYMERIC MICELLES FOR GENE-DIRECTED ENZYME PRODRUG THERAPY

Gene-directed enzyme prodrug therapy is a form of cancer therapy in which delivery of a gene that encodes an enzyme is able to convert a prodrug, a pharmacologically inactive molecule, into a potent cytotoxin. Currently delivery of gene and prodrug is a two-step process. Here, we propose a one-step method using polymer nanocarriers to deliver prodrug, gene and cytotoxic drug simultaneously to malignant cells. Prodrugs acyclovir, ganciclovir and 5-doxifluridine were used to directly to initiate ring-opening polymerization of epsilon-caprolactone, forming a hydrophobic prodrug-tagged poly(epsilon-caprolactone) which was further grafted with hydrophilic polymers (methoxy poly(ethylene glycol), chitosan or polyethylenemine) to form amphiphilic copolymers for micelle formation. Successful synthesis of copolymers and micelle formation was confirmed by standard analytical means. Conversion of prodrugs to their cytotoxic forms was analyzed by both two-step and one-step means i.e. by first delivering gene plasmid into cell line HT29 and then challenging the cells with the prodrug-tagged micelle carriers and secondly by complexing gene plasmid onto micelle nanocarriers and delivery gene and prodrug simultaneously to parental HT29 cells. Anticancer effectiveness of prodrug-tagged micelles was further enhanced by encapsulating chemotherapy drugs doxorubicin or SN-38. Viability of colon cancer cell line HT29 was significantly reduced. Furthermore, in an effort to develop a stealth and targeted carrier, CD47-streptavidin fusion protein was attached onto the micelle surface utilizing biotin-streptavidin affinity. CD47, a marker of self on the red blood cell surface, was used for its antiphagocytic efficacy, results showed that micelles bound with CD47 showed antiphagocytic efficacy when exposed to J774A.1 macrophages. Since CD47 is not only an antiphagocytic ligand but also an integrin associated protein, it was used to target integrin alpha(v)beta(3), which is overexpressed on tumor-activated neovascular endothelial cells. Results showed that CD47-tagged micelles had enhanced uptake when treated to PC3 cells which have high expression of alpha(v)beta(3). The synthesized multifunctional polymeric micelle carriers developed could offer a new platform for an innovative cancer therapy regime.