Browsing by Subject "Regulation"

Autonomous systems are emerging across many industries. From unmanned aircraft to self-driving cars to closed-loop medical devices, these systems offer great benefits but also pose new risks. Regulators must grapple with how to manage these risks, challenged to keep pace with technological developments and exhibit appropriate precaution without stifling innovation. Seeking inspiration for a viable approach to the regulation of autonomous systems, this thesis draws from the practices of systems engineering, an interdisciplinary field of engineering aimed at managing the risks of complex projects. By comparing systems engineering practices to regulatory options, current regulations, and the inherent challenges of regulating emerging technologies, this thesis concludes that a systems engineering-based approach to regulating autonomous systems offers great potential for managing the risks of autonomous systems while also driving innovation.

In the 1970s, consumer advocates worried that Alabama's weak regulatory structure around consumer fraud made it a kind of "con man's heaven." But by the 1990s, the battle cry of regulatory reformers had reversed, as businesspeople mourned the state's decline into "tort hell." Debates about the correct balance of power among consumers, businesses, and the state continue to shape political contests in both Alabama and on the broader national stage today, whether contextualized under the aegis of "consumer protection," "access to justice," "tort reform," protecting "free enterprise," or cultivating a positive "business climate."

This dissertation argues for analyzing such matters in terms of a regulatory ecology, following the interconnections across institutions, including formal rules of civil procedure as well as informal codes of conduct, that shape the law of lawsuits within the American civil justice system. Drawing on case files, interviews, and archival sources, it traces the development of Alabama's first consumer-protection law and regulatory agency in the early 1980s, the construction and deconstruction of a comprehensive state tort-reform package in 1987, the rise of tort lawsuits and its invigoration of Alabama's trial-lawyer bar, and the transformation of the Alabama Supreme Court in the 1990s. It then analyzes how political narratives, fashioned in part by powerful business lobbies, molded the terms of the tort-reform debate at the state and national levels in ways that effectively swayed public opinion and created favorable conditions for successful tort reform legislation.

The dissertation does not propose a regulatory agenda; rather, it concludes that interdisciplinary perspectives on regulatory governance, drawing insights from legal, political, and business history as well as other social science disciplines, better frame problems than more simplistic assessments of tort reform. Tort lawsuits blossomed in Alabama where other avenues for resolving regulatory issues or expressing dissent closed. Tort reform is likely to unleash new pressures for addressing perceived instances of unfairness in the marketplace.

The essays in housing markets contained within this dissertation examine the effect of policy decisions on housing market outcomes in the emerging market context of China and the developed market context of US. Specifically, I estimate the effect of demand- and supply-side quantitative allocation policies on the price elasticity of housing supply and the home price volatility across municipalities in China. At the transaction level, I use Chinese land supply data to examine the substitution of land use types, and present evidence on politically driven land supply decisions that favor industrial land use and specific industries to increase local officials’ promotion probabilities. For the US mortgage market, I leverage a unique dataset from Freddie Mac’s national mortgage lender survey to examine the effect of quantitative easing on mortgage-backed securities pricing and primary mortgage rates. I find that large-scale purchases of mortgage-backed securities by the Federal Reserve is associated with substantial declines in mortgage rates across the country, but local economic and housing conditions are also important contributing factors to cross-sectional dispersion in mortgage rates. The combined results of these essays reveal policy decisions can have significant impact on housing market outcomes and provide directions for future research.

This dissertation studies three questions in labor economics centering around immigration policy and its effects on vulnerable populations. I use administrative data from the United States (U.S.) and Germany to address these questions empirically.

In the first chapter, I investigate the effects of an increase in immigration enforcement through local police force on domestic violence victims’ help-seeking behavior. I use a fixed effects model, a generalized synthetic control method and novel administrative data on the use of services for domestic violence victims in North Carolina. In North Carolina, a large fraction of individuals of Hispanic origin are undocumented immigrants or connected to undocumented immigrants. I find that local immigration enforcement significantly reduces Hispanics’ use of domestic violence services. It does not affect service use by African Americans who are predominantly U.S.-born citizens. This suggests that the decrease in Hispanics' service use is directly related to their immigration status and not driven by a general effect on minorities. I do not find any robust evidence that local immigration enforcement affects intimate partner homicides of Hispanic women.

The second chapter studies the relationship between workforce demographics, workplace hazard, and worker complaints about hazardous or illegal working conditions. In joint work with Matthew Johnson, I examine if worker complaints are effective in directing inspections by the U.S. Occupational Safety and Health Administration to the most hazardous workplaces. We measure worker complaints and workplace injuries by inspections triggered by a worker complaint and a serious workplace injury, respectively. We find that the complaint rate in a county and industry is positively associated with its recent injury rate. This relationship changes for workplaces with a high share of Hispanic workers. Workplaces that employ larger shares of Hispanic workers have lower complaint rates, but higher injury rates. We use fixed effects regressions to estimate the effect of local immigration enforcement on Hispanic workers' willingness to complain about hazardous conditions. We find that stronger enforcement significantly reduces worker complaints, but not workplace injuries in workplaces with a high share of Hispanic workers. This provides evidence that stronger local immigration enforcement reduces Hispanic workers' willingness to complain about unsafe working conditions irrespective of the true workplace hazard.

In the third chapter, I investigate the effect of integrating refugee students in elementary schools on the academic performance of native students. Using administrative data from Germany, I exploit the variation in the percentage of refugee students within schools to account for endogenous sorting of refugees into schools. I do not find any evidence for negative effects of refugee students' integration on the academic performance of native elementary students. In contrast, exposure to refugee students reduces mandatory grade retention rates of German fourth graders. Effects on the percentage of students who receive a recommendation for the higher secondary track are very small and statistically insignificant. I also show that refugee students attend schools where German students' performance is lower.

N6-methyladenosine (m6A) is deposited co-transcriptionally on thousands of cellular mRNAs and plays important roles in mRNA processing and cellular function. m6A is particularly abundant within the brain and is critical for neurodevelopment. However, the mechanisms through which m6A contributes to brain development are inco¬¬mpletely understood. Here, we discover serine-/arginine-rich splicing factor 7 (SRSF7) and RNA-binding motif-containing protein 45 (RBM45) as m6A-binding proteins in transformed hippocampal neurons. We find that SRSF7 binds to exon-intron junctions in methylated pre-mRNA targets and regulates the gene expression of thousands of cellular mRNAs, including the m6A RNA methyltransferase, METTL3. We find that RBM45 binds to thousands of cellular RNAs, predominantly within intronic regions. Rbm45 depletion disrupts the constitutive splicing of a subset of target pre-mRNAs, leading to altered mRNA and protein levels through both m6A-dependent and m6A-independent mechanisms. Finally, we find that RBM45 is highly expressed during embryonic neurodevelopment, demonstrating that expression of RBM45 is necessary for neuroblastoma cell differentiation and that its depletion impacts the expression of genes involved in several neurodevelopmental signaling pathways. Altogether, our findings identify roles for SRSF7 and RBM45 in gene expression regulation, and highlight a previously unknown function for RBM45 in the control of pre-mRNA processing and neuronal differentiation, mediated in part by the recognition of methylated RNA.

Since the inception of recombinant protein expression, this technique has revolutionized our everyday lives with the number of protein products we have at our disposal ranging from household products to pharmaceuticals. E. coli was the first host used for recombinant protein expression and it has remained a mainstay expression host in biotechnology. However, the utility of E. coli as an expression host is limited by challenges that, if addressed, would make it a more suitable host for a wider variety of proteins, and thereby catalyze the translation of more protein products. Here, we address these challenges with dynamic control of the E. coli metabolism. This approach involves decoupling cell growth and protein expression and altering metabolism exclusively in the production phase. With this dynamic tool we have been able to: (1) engineer E. coli to improve the cytoplasmic solubility of redox sensitive proteins that are prone to aggregation, (2) improve the growth robustness of these engineered strains over the current state the art, (3) simply the bioprocess to purify these redox sensitive proteins, (4) identify uncharacterized redox regulation that impacts protein expression. Additionally, we provide a historical overview of biotechnological advances associated with a class of biopharmaceuticals, enzyme-based therapies, which have underutilized potential. Cumulatively, this work analyzes development trends of biologics, recognizes gaps in therapeutic and production capabilities, and provides solutions to challenges associated with redox sensitive protein expression and purification in E. coli.

Transnational governance has been advanced as a viable option for regulating commodities produced in emerging economies—where incapable or unwilling states may undersupply institutions requisite for overseeing supply chains consistent with the quality, safety, environmental, or social standards demanded by the global marketplace. Producers from these jurisdictions, otherwise left with few venues for securing market access and price premiums, ostensibly benefit from whatever pathways transnational actors offer to minimize barriers to entry—including voluntary certification for compliance with a panoply of public and private rules, such as those promulgated by NGOs like the Fair Trade Federation or multinational retailers like Wal-Mart. Yet, such transnational “sustainability” governance may neither be effective nor desirable. Regulatory schemes, like third-party certification, often privilege the interests of primary architects and beneficiaries—private business associations, governments, NGOs, and consumers in the global North—over regulatory targets—producers in the global South. Rather than engaging with the international marketplace via imported and externally-driven schemes, some producer groups are instead challenging existing rules and innovating homegrown institutions. These alternatives to commercialization adopt some institutional characteristics of their transnational counterparts yet deliver benefits in a manner more aligned with the needs of producers. Drawing on original empirical cases from Nicaragua and Mexico, this dissertation examines the role of domestic institutional alternatives to transnational governance in enhancing market access, environmental quality and rural livelihoods within producer communities. Unlike the more technocratic and expert-driven approaches characteristic of mainstream governance efforts, these local regulatory institutions build upon the social capital, indigenous identity, “ancestral” knowledge, and human assets of producer communities as new sources of power and legitimacy in governing agricultural commodities.

My dissertation seeks to understand how and why governments make major changes in financial sector regulations. I focus on two specific puzzles. First why is financial sector regulation not normally central to electoral competition and why are changes in financial sector regulation rare events? Second, why do we observe substantive intellectual debates and efforts of policy persuasion despite the conclusion of many researchers and observers that financial regulatory policy outcomes are driven by the preferences of powerful special interest groups? What are the mechanisms precisely by which ideas versus interests shape policy outcomes in a domain that is not often central to electoral politics? I investigate these questions through a formal game theoretical model of the regulatory policymaking process and through case studies of historic episodes of financial regulatory change in the United States which draw upon a wide variety of primary and secondary source historical materials. I conclude that financial regulatory change is most likely to occur when events of different types cause heads of government to perceive that the existing regulatory status quo threatens the realization of broader policy objectives. Heads of financial sector policy bureaucracies shape outcomes by providing cognitive frameworks through which leaders understand regulatory consequences. Interest groups influence policy outcomes primarily through their ability to act as veto players rather than by controlling the policy agenda.

The TMEM16 protein family comprises two novel classes of structurally conserved but functionally distinct membrane transporters that function as Ca2+-dependent Cl- channels (CaCCs) or dual functional Ca2+-dependent ion channels and phospholipid scramblases. The TMEM16A and TMEM16B CaCCs conduct Cl- across the membrane and regulate transepithelial fluid transport, smooth muscle contraction, neuronal excitability and sensory signal transduction. Most other TMEM16 members are scramblases that mediate the flip-flop of phospholipids across the membrane to allow phosphatidylserine externalization, which is essential in a plethora of important processes such as blood coagulation, bone development and viral and cell fusion. Activation of TMEM16 proteins requires the binding of intracellular Ca2+ to two highly conserved orthosteric binding sites in transmembrane helices (TM) 6-8 opens the permeation pathway formed by TMs 3-7. However, prolonged Ca2+-dependent simulation of TMEM16 channels results in current desensitization or rundown, the mechanism of which is unclear. In addition, recent structural studies of TMEM16 scramblases revealed yet another Ca2+ binding site in TM2 and TM10 whose functional relevance remains unknown. By combining electrophysiology, systematic mutagenesis and molecular dynamics simulation, we first demonstrate that the phosphatidylinositol-(4,5)-bisphosphate (or PI(4,5)P2) plays a critical role in TMEM16A’s Ca2+-dependent activation and desensitization. We identify key basic residues at the cytosolic interface of transmembrane segments (TMs) 3–5 as the putative PI(4,5)P2-binding site, which is supported by our molecular dynamics studies. These studies reveal that TMEM16A is constituted of two functionally distinct modules: a Ca2+-binding module formed by TMs 6–8 and a PI(4,5)P2-binding regulatory module formed by TMs 3–5, which mediate channel activation and desensitization, respectively. Next, we show that Ca2+ binds with high affinity to the putative third Ca2+ site in TM2 and TM10 of TMEM16A to enhance channel activation. Our cadmium (Cd2+) metal bridging experiments further show that the third Ca2+ site’s conformational states can profoundly influence TMEM16A’s opening. Taken together, our studies not only establish the molecular bases for the PI(4,5)P2-dependent regulation of TMEM16A and the long-range allosteric gating mechanism via the third Ca2+ binding site; they also provide functional insight into the structural organization of TMEM16 ion channels and lipid scramblases.

Retirement is the quintessential transition from mid-life to late-life for many working Americans. However, questions about the positive and negative effects of retirement have sparked widely divergent empirical findings. Developmental theories of self-regulation may add to the understanding of the subtle differences and transitions within retirement. Retirement may be viewed as a transition in resources (e.g., psychological, social, and financial), so that individual mental health outcomes are linked to how well these resources are reallocated. According to goal disengagement perspectives, failure either in disengagement from past goals or reengagement in new goals can lead to decreased well-being and increased depression. Further, as individuals enter late-life, their focus may turn away from growth and achievement and more toward preventing losses and maintaining current resources. In the present study, it was hypothesized that when pre-retirement individuals were compared against early and late post-retirement individuals, engagement in developmentally relevant goals (e.g., self, family, and leisure) in retirees would be associated with better mental health outcomes while retirees who reported continued engagement in less developmentally accessible goals (i.e., occupational and financial) would report worse outcomes.

A total of 100 study participants (aged 50 to 84) were interviewed about their current goals and completed self-report measures of depression, well-being, social support, physical health, and regulatory focus. Interview data were coded for goal content as well as for regulatory focus. Findings did not support the hypotheses, as there were no significant differences among the 47 pre-retirement, 29 early post-retirement, and 24 late post-retirement participants in their goal content or regulatory focus. Goal content also was not associated differentially with depression or well-being among the three groups. However, the interview data did provide valuable information about the heterogeneous and fluid nature of retirement. Retirement, rather than a clear loss in certain resources (i.e., financial and occupational) and a clear gain in others (i.e., time and personal freedom), seemed to be a renegotiation of those resources. Furthermore, even pre-retirement participants named retirement goals, suggesting that, if a goal transition did occur, it may have been a more conscious, gradual process.

Cis-elements govern the key step of transcription to regulate gene expression within a cell. Identification of utilized elements within a particular cell line will help further our understanding of individual and cumulative effects of trans-acting factors. These elements can be identified through an assay leveraging the ability of DNaseI to cut DNA that is in an open and accessible state making it hypersensitive to cleavage. Here we develop and explore computational techniques to measure open chromatin from sequencing and microarray data. We are able to identify 94,925 DNaseI hypersensitive sites genome-wide in CD4+ T cells. Interestingly, only 16%-20% of these sites were found in promoters. We also show that these regions are associated with different chromatin modifications. We found that DNaseI data can also be used to identify precise 'footprints' indicating protein-DNA interaction sites. Footprints for specific transcription factors correlate well with ChIP-seq enrichment, reveal distinct conservation patters, and reveal a cell-type specific arrangement of transcriptional regulation. These footprints can be used in addition to or in lieu of ChIP-seq data to better understand genomic regulatory systems.