In this thesis I argue that the management of Muslim pilgrims and the Haj traffic in Bombay was the result of the localization of an international regime of regulation aimed at controlling Hajis as mobile threats to public health and imperial security. International scientists, doctors, and politicians problematized Hajis as diseased, dangerous and disorderly through discourse produced in print material and at international conferences taking place across the globe. Local, elite concerns over their own power, Bombay’s urban spatial order, and the city’s international trade shaped the way these larger global and imperial projects were implemented in Bombay. These findings point to the importance of local, place-based social, political and economic structures in the day-to-day governance of empire.

One-carbon metabolism is an essential process that is conserved from yeast to humans. Glycine stimulates the expression of genes in one-carbon metabolism, whereas its withdrawal causes repression of these genes. The transcription factor Bas1p and the metabolic enzyme Shm2p have been implicated in this regulation. I have shown that Bas1p physically interacts with Shm2p through co-immunoprecipitation. Using chromatin immunoprecipitation (ChIP), I have also shown that the interaction between Bas1p and Shm2p occurs at the promoter of two genes in the one-carbon metabolism regulon and that the binding of Shm2p requires Bas1p. Using a yeast-two hybrid system, I have systematically truncated Bas1p from the C-terminal end to find a region responsible for the interaction with Shm2p. My data suggest that Shm2p is directly bound to Bas1p at the promoters of glycine regulated genes where it regulates the transcriptional activity of Bas1p in response to changes in glycine levels.

This paper will consider how regulatory arbitrage contributed to the 2007-2009 financial crisis (the “financial crisis”). In particular, the paper will establish how the avoidance of regulatory capital requirements by large and complex financial institutions (“LC financial institutions”) severely worsened the financial crisis, necessitating a massive rent extraction from U.S. taxpayers. In doing to, the paper will examine the regulatory arbitrage perpetrated by American International Group and the subsequent U.S. taxpayer bailout of that firm. Because of the enormous amount of sovereign credit that had to be substituted for private capital during the financial crisis the paper assumes that the net negative nature of regulatory avoidance by LC financial institutions is axiomatic. Therefore, the paper advances several possible reform measures that could eventually be implemented into a new legal framework to confront the problems that are posed by the avoidance of financial services regulations.

The Alternative Investment Fund Managers Directive ("AIFMD"), adopted by the European Union on 11 November 2010, has introduced a harmonized set of rules for alternative investment funds (“AIFs”) in Europe. This thesis discusses potential financial risks for the AIFs industry arising from the European regulatory reform, which started before the current financial crisis, and compares relevant European, Canadian and US rules governing AIFs. This comparative analysis is based on four main criteria: i) registration and authorization requirements, ii) general financial transparency requirements, iii) capital requirements, and iv) remuneration restrictions. The analysis of AIFs regulatory reform in Europe leads to three main conclusions. First, the AIFMD requirements are much stricter than analogue regimes in Canada and the United States. Second, as a consequence of this regulation, European AIFs may be in disadvantage. Third, the complexity of the present European institutional framework is not able to fully implement the European regulatory reform.

In this thesis I argue that the management of Muslim pilgrims and the Haj traffic in Bombay was the result of the localization of an international regime of regulation aimed at controlling Hajis as mobile threats to public health and imperial security. International scientists, doctors, and politicians problematized Hajis as diseased, dangerous and disorderly through discourse produced in print material and at international conferences taking place across the globe. Local, elite concerns over their own power, Bombay’s urban spatial order, and the city’s international trade shaped the way these larger global and imperial projects were implemented in Bombay. These findings point to the importance of local, place-based social, political and economic structures in the day-to-day governance of empire.

The chapters of this dissertation explore related aspects of the procurement of conservation services from private landowners. In the first chapter, heuristic laboratory experiments reveal the impact of potential government regulation on strategic forces and efficiency properties in conservation procurement auctions. In the second chapter, data from past procurement auctions are analyzed to discover the existence and magnitude of premiums received by auction participants. The first Chapter, “Procurement Auctions Under Regulatory Threat,” examines how strategic forces and efficiency properties are impacted in auctions for the procurement of environmental services when a threat of regulation is levied. Laboratory experiments examining different regulatory environments demonstrate that a threat of regulation will reduce the amount of public funds necessary to purchase a given level of environmental services. However, adverse selection costs and equity are negatively impacted by threat implementation. The second Chapter, “Estimating Bid Inflation in Procurement of Environmental Services,” studies the size of premiums received by program participants in conservation programs. Predictions informed by economic literature and theory elicit the underlying value distribution for a unique dataset of procurement auctions. Average premiums for auction participants range from almost 50 percent to less than 1 percent across auction periods and institutions. The results demonstrate that both repetition and rule variation may improve the efficiency of procurement auctions. The auctions studied here are shown to yield efficiency improvements of more than 32 percent over standard fixed-payment schemes for service procurement.

In addition to previously identified roles for RNA, several new ways in which RNA serves as a regulator of gene expression have recently been described. RNA molecules are involved in both transcriptional and post-transcriptional forms of regulation, sometimes heritably affecting gene activity. Whereas most previously characterized regulatory roles of RNA involve downregulation, I describe a role for maternal transcripts of a gene in promoting zygotic activity of that gene, which I term the licensing of genetic activity. This regulation occurs in the germ line, a tissue notable for its abundance of genetic surveillance mechanisms. The maternal-effect regulation described here was identified using alleles of a sex-determining gene in Caenorhabditis elegans called fem-1. Females homozygous for fem-1 deletions produce heterozygous offspring that exhibit germ-line feminization and have reduced fem-1 activity and transcript accumulation. This phenotype can be rescued by injecting fem-1 RNA into the maternal germ line. The reduction in activity of the zygotic fem-1 locus is heritable, suggesting that the gene is becoming epigenetically silenced. Thus the maternal fem-1 RNA licenses the activity of the zygotic locus by preventing its silencing. By restricting germ-line activity to genes that were expressed in the germ line of the previous generation, this process may contribute to protecting the identity and integrity of the germ line. I performed an RNAi screen of candidate genes to ask whether they are required for maternal-effect silencing or licensing. Several enhancers and suppressors of germ-line feminization in the descendants of fem-1 deficiency homozygotes were identified. Chromatin regulation may be involved, and small-RNA pathways are important for both the silencing and licensing components of fem-1 regulation. Based on my characterization of this phenomenon, I proposed models of how maternal-effect regulation of fem-1 may be mediated. To test predictions of certain models, I examined whether specific characteristics of fem-1 make it susceptible to this silencing. Results of these experiments limit the possible models of maternal-effect regulation and suggest directions for future investigation.

The shikimate pathway is a primary metabolic pathway involved in the synthesis of aromatic compounds in plants, fungi, apicomplexan parasites and microbes. The absence of this pathway in animals makes it ideal for the synthesis of antimicrobial compounds and herbicides. Additionally, its branching into indole hormone synthesis and phenylpropanoid secondary metabolism makes this pathway attractive for metabolic engineering. Here, the focus is on the first step of the shikimate pathway catalyzed by DAHP synthase. This step consists of the condensation of phosphoenol pyruvate and erythrose-4-phosphate to make DAHP, which undergoes another six catalytic steps to synthesize chorismate, the precursor of the aromatic amino acids. Arabidopsis thaliana contains three DAHP synthase isozymes, which are known to indirectly regulate downstream pathways in response to wounding and pathogen stress. The model presented here proposes that DAHP synthase isozymes are regulated by the end products tyrosine, tryptophan and phenylalanine.

p53 functions as an important tumour suppressor through its ability to regulate a number of important cellular processes such as cell cycle arrest, apoptosis, DNA repair, senescence, and angiogenesis. An in vivo genetic modifier screen performed using Drosophila melanogaster resulted in the identification of D. melanogaster brain tumour (brat) as a putative modifier of of the p53 small eye phenotype. Mammalian homologs of brat are members of the tripartite motif family that contain a c-terminal NHL domain. We focus on elucidating the in vivo role of one such homolog, BERP, through the generation and characterization of a classical gene-deletion mouse mutant. We report that BERP-deficient mice exhibit enhanced learning/memory, increased fear, impaired motor coordination, and increased resistance to PTZ -induced seizures. Electrophysiological and biochemical studies show a decrease in mIPSC amplitude along with a decrease in cell surface expression of gamma2 subunit-containing GABA A receptors in the brains of BERP-deficient mice. In addition, no effect of genotype is apparent when examining BERP mRNA levels in the brain. This suggests that the decreased cell surface expression of gamma2 subunit-containing GABA A receptors is likely a posttranscriptional phenomenon and supports the possibility that BERP may be involved in the intracellular trafficking of GABA A receptors. In investigating the possible relationship between BERP and p53, we identify the presence of a transcriptionally competent p53 response element within the first intron of the human BERP genomic locus and demonstrate that the BERP expression is up regulated in a p53-dependent manner both in vitro and in vivo. These results support the interpretation that BERP is a novel p53-regulated gene and suggest a new role for p53 in the regulation of GABA A receptor trafficking and epileptogenesis.

In addition to previously identified roles for RNA, several new ways in which RNA serves as a regulator of gene expression have recently been described. RNA molecules are involved in both transcriptional and post-transcriptional forms of regulation, sometimes heritably affecting gene activity. Whereas most previously characterized regulatory roles of RNA involve downregulation, I describe a role for maternal transcripts of a gene in promoting zygotic activity of that gene, which I term the licensing of genetic activity. This regulation occurs in the germ line, a tissue notable for its abundance of genetic surveillance mechanisms. The maternal-effect regulation described here was identified using alleles of a sex-determining gene in Caenorhabditis elegans called fem-1. Females homozygous for fem-1 deletions produce heterozygous offspring that exhibit germ-line feminization and have reduced fem-1 activity and transcript accumulation. This phenotype can be rescued by injecting fem-1 RNA into the maternal germ line. The reduction in activity of the zygotic fem-1 locus is heritable, suggesting that the gene is becoming epigenetically silenced. Thus the maternal fem-1 RNA licenses the activity of the zygotic locus by preventing its silencing. By restricting germ-line activity to genes that were expressed in the germ line of the previous generation, this process may contribute to protecting the identity and integrity of the germ line. I performed an RNAi screen of candidate genes to ask whether they are required for maternal-effect silencing or licensing. Several enhancers and suppressors of germ-line feminization in the descendants of fem-1 deficiency homozygotes were identified. Chromatin regulation may be involved, and small-RNA pathways are important for both the silencing and licensing components of fem-1 regulation. Based on my characterization of this phenomenon, I proposed models of how maternal-effect regulation of fem-1 may be mediated. To test predictions of certain models, I examined whether specific characteristics of fem-1 make it susceptible to this silencing. Results of these experiments limit the possible models of maternal-effect regulation and suggest directions for future investigation.