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The trichothecene mycotoxins are secondary metabolites produced by a variety of fungal genera including Fusarium, Myrothecium, Trichothecium, and Stachybotyris, that are toxic to humans and animals that ingest them by consumption of contaminated grain. This work details the characterization of a novel regulatory gene from Fusarium sporotrichioides, Tri10, which is located in the trichothecene gene cluster. Northern analysis of Tri10 deletion strains, Tri10 overexpressing strains, and a Tri6 deletion strain indicated that Tri10 is required for wild-type trichothecene gene expression and for wild-type expression of a primary metabolic gene, Fpps. Analysis of these mutants also provided evidence for a regulatory feedback loop where Tri10 is required for the expression of Tri6 and Tri6 negatively regulates Tri10. Furthermore, under certain growth conditions the sensitivity of ΔTri10 and ΔTri6 strains to T-2 toxin was increased. Analysis of mutants altered in the expression and genomic position of Tri10 revealed that placing Tri10 under the control of an exogenous promoter resulted in the overexpression of Tri10 and the other Tri genes whether this construct was located inside or outside of the Tri gene cluster. Work outside of this study has shown that in addition to Fpps, three other primary metabolic genes from the isoprenoid pathway feeding into trichothecene biosynthesis (Acat, Mk, Hmgs) are also influenced by the expression of Tri10 and Tri6. In the present study, targeted cDNA microarrays were used in conjunction with multiple mutants to reveal a large group of genes, containing both trichothecene and primary metabolic genes, which were positively influenced by Tri10 expression. At the same time, a small group of genes negatively influenced by Tri10 expression was observed. These results were in agreement with observations made outside of this study and validated the use of targeted cDNA microarrays for further studies. Additional analysis of the regulatory network linking trichothecene secondary metabolism and isoprenoid primary metabolism revealed that in a mutant blocked in the first step of the pathway, and therefore in the absence of trichothecene production, this regulatory link is mediated by Tri10 and Tri6.

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Identification and characterization of regions influencing the precise spatial and temporal expression of genes is critical to our understanding of gene regulatory networks. Connecting transcription factors to the cis-regulatory elements that they bind and regulate remains a challenging problem in computational biology. The rapid accumulation of whole genome sequences and genome-wide expression data, and advances in alignment algorithms and motif-finding methods, provide opportunities to tackle the important task of dissecting how genes are regulated. Genes exhibiting similar expression profiles are often regulated by common transcription factors. We developed a method for identifying statistically over-represented regulatory motifs in the promoters of co-expressed genes using weight matrix models representing the specificity of known factors. Application of our methods to yeast fermenting in grape must revealed elements that play important roles in utilizing carbon sources. Extension of the method to metazoan genomes via incorporation of comparative sequence analysis facilitated identification of functionally relevant binding sites for sets of tissue-specific genes, and for genes showing similar expression in large-scale expression profiling studies. Further extensions address alternative promoters for human genes and coordinated binding of multiple transcription factors to cis-regulatory modules. Sequence conservation reveals segments of genes of potential interest, but the degree of sequence divergence among human genes and their orthologous sequences varies widely. Genes with a small number of well-distinguished, highly conserved non-coding elements proximal to the transcription start site may be well-suited for targeted laboratory promoter characterization studies. We developed a “regulatory resolution” score to prioritize lists of genes for laboratory gene regulation studies based on the conservation profile of their promoters. Additionally, genome-wide comparisons of vertebrate genomes have revealed surprisingly large numbers of highly conserved non-coding elements (HCNEs) that cluster nearby to genes associated with transcription and development. To further our understanding of the genomic organization of regulatory regions, we developed methods to identify HCNEs in insects. We find that HCNEs in insects have similar function and organization as their vertebrate counterparts. Our data suggests that microsynteny in insects has been retained to keep large arrays of HCNEs intact, forming genomic regulatory blocks that surround the key developmental genes they regulate.

This thesis models rational criminals and regulators with flawed incentives. In it we develop a rational model of crime and regulation that we use to show the SEC's current incentive structure is ineffective at preventing fraud. Under our model, criminals balance the monetary rewards of larger frauds against an increased chance of being apprehended; and regulators design regulations to minimize either the damage caused by fraud or some other metric. We show that under this model, the SEC's focus on 'stats' and 'quick hits' leads to large frauds and a large social loss. We argue that regulators need to focus not just on successful prosecutions, but also on harm reduction and deterrence.

This thesis examines the best system for health professions regulation in Ethiopia with a view to sketch the roles of state and non-state actors in that system. It argues for statist regulation as self-regulation is worrisome for its tendency to promote private interest instead over public protection. A statist regulation is an efficient system that is more capable of establishing accountable and procedurally fair processes and strengthening public trust than a system of self-regulation. But the state lacks capacity, expertise, and legitimacy, and risks capture and corruption. These could be resolved through an enforcement strategy rooted in responsive regulation theory. That strategy should emphasize soft regulatory instruments, which requires utilization of the capacity and motivation of non-state actors, particularly health professional associations. A statist regulatory framework that harnesses the contribution of non-state actors in implementing soft regulatory strategies would effectively protect patients and improve the quality of health care services in Ethiopia.

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Scholars and midwives agree that women’s autonomy over decisions related to birth is not being respected in a country where there is mainly one birth setting and one type of provider, in particular, when this setting and provider are often link to the use of unnecessary and excessive medical interventions. This is the case of Puerto Rico. I argue that midwifery could be an answer to this problem. Midwifery in Puerto Rico is not yet regulated, but I claim that in order to promote Puerto Rican women’s autonomy, midwifery regulation has to be well thought. This thesis includes an analysis of a bill proposed in Puerto Rico that pretended to regulate midwifery. Submissions presented to the legislature are also analyzed and criticized in this thesis. Some recommendations are provided on how Puerto Rico can enact a sensible scheme of midwifery regulation that would enhance midwives autonomy and therefore women’s autonomy.