Conservation implications of the reproductive biology of the endangered vine Ipomoea microdactyla Griseb. (Convolvulaceae)

A plant's reproductive biology exerts a significant influence on both population persistence within changing environments and successful establishment of new populations. However, the interaction between extrinsic (i.e. ecological) and intrinsic (i.e. genetic) factors also is an important driver of demographic performance for plant populations. It is light of this that I performed a multidisciplinary investigation of the breeding system, seed and seedling establishment dynamics, and population genetic structure of the endangered Caribbean vine Ipomoea microdactyla Griseb. (Convolvulaceae). The results from the breeding system study show individuals from Florida, USA and Andros Island, Bahamas to be self-incompatible. Plants from the two regions are cross-compatible but there is evidence for outbreeding depression in their progeny. Significant regional differences were found in floral traits and progeny traits that suggests incipient speciation for the Florida populations. The results from the seed and seedling establishment dynamics experiment demonstrate that the restoration of small populations in Florida via seed and seedling augmentation is a successful strategy. The demographic performance of the outplanted individuals was driven significantly by ecological factors (e.g. herbivory) rather than by genetic factors which emphasizes that the ecological context is very important for successful restoration attempts. The results from the population genetic study using an analysis of molecular variation (AMOVA) reveal significant differences in genetic variation among individuals from Florida, Andros, and Cuba. A Bayesian analysis of population genetic structuring coincided with the previous AMOVA results among the three regions. The Mantel test indicated significant 'isolation by distance' for these regional populations implying restricted gene flow over relatively short distances. Overall, the Florida populations had the lowest measures of genetic diversity which is most likely due to the effects of both colonization founder events and habitat fragmentation. The results of my study highlight the value of performing multidisciplinary studies in relation to species conservation as knowledge of both extrinsic and intrinsic factors can best guide decisions for species preservation.

Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors.

Three Essays on a Longitudinal Analysis of Business Start-ups using the Kauffman Firm Survey

This dissertation focused on the longitudinal analysis of business start-ups using three waves of data from the Kauffman Firm Survey. The first essay used the data from years 2004-2008, and examined the simultaneous relationship between a firm’s capital structure, human resource policies, and its impact on the level of innovation. The firm leverage was calculated as, debt divided by total financial resources. Index of employee well-being was determined by a set of nine dichotomous questions asked in the survey. A negative binomial fixed effects model was used to analyze the effect of employee well-being and leverage on the count data of patents and copyrights, which were used as a proxy for innovation. The paper demonstrated that employee well-being positively affects the firm's innovation, while a higher leverage ratio had a negative impact on the innovation. No significant relation was found between leverage and employee well-being. The second essay used the data from years 2004-2009, and inquired whether a higher entrepreneurial speed of learning is desirable, and whether there is a linkage between the speed of learning and growth rate of the firm. The change in the speed of learning was measured using a pooled OLS estimator in repeated cross-sections. There was evidence of a declining speed of learning over time, and it was concluded that a higher speed of learning is not necessarily a good thing, because speed of learning is contingent on the entrepreneur's initial knowledge, and the precision of the signals he receives from the market. Also, there was no reason to expect speed of learning to be related to the growth of the firm in one direction over another. The third essay used the data from years 2004-2010, and determined the timing of diversification activities by the business start-ups. It captured when a start-up diversified for the first time, and explored the association between an early diversification strategy adopted by a firm, and its survival rate. A semi-parametric Cox proportional hazard model was used to examine the survival pattern. The results demonstrated that firms diversifying at an early stage in their lives show a higher survival rate; however, this effect fades over time.