Browsing by Subject "Regulation"

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Adrenergic regulation of CFTR-dependent anion secretion and cell migration in airway epithelial cells
(2014-12) Peitzman, Elizabeth Ruth
The overall goal of this thesis was to understand the mechanisms underlying beta-adrenergic receptor (beta-AR) regulation of anion secretion and epithelial cell migration on mucociliary clearance and epithelial repair in human airways. The first chapter of the thesis presents an overview of the literature with the purpose of providing background information of mucociliary clearance, airway epithelial cell restitution and specific inflammatory disease conditions where these processes contribute to the innate defense of the airways. Chapters 2 and 3 describe the methods, results and a discussion of experiments that were performed to address the overall goal of the thesis. The final chapter presents a general discussion of the major findings of these studies in the context of what is presently known about the role of beta-AR regulation of epithelial function in airways. Initial experiments presented in Chapter 2 so looked at the effects of growth conditions on beta-AR localization in a human airway epithelial cell model system (Calu-3 cells). The results from these experiments showed that under air-liquid interface (ALI) conditions basolateral stimulation with 1uM epinephrine produced a significant increase in CFTR dependent anion secretion, whereas cells that were grown under liquid liquid interface (LLI) had a much smaller increase secretion when stimulated with the same concentration of epinephrine. These results indicated that basolateral expression of beta-ARs is increased when cells were grown under ALI. Furthermore Calu-3 cells that were apically stimulated with the beta2-AR selective agonist salbutamol produced an increase in anion secretion similar to what was observed with 8cpt-cAMP, a non-metabolizable analog of cyclic AMP. Additionally, when cells were treated with carvedilol, an inverse agonist acting at beta2-ARs, an initial decrease in basal Isc occurred and carvedilol treatment after stimulation with 8cpt-cAMP inhibited anion secretion. Cells pretreated with nocotazole, an agent that disrupts microtubule assembly, blocked the inhibitory effects of carvedilol on anion secretion, suggesting that endocytosis was necessary in order to observe the inhibitory effects of carvedilol. Finally, western blot analysis of apical membrane proteins showed that when cells were treated with carvedilol there was reduced expression of CFTR in the apical membrane, which was not observed following stimulation with epinephrine.Experiments in chapter 3 were designed to investigate the effects of beta-AR agonists on epithelial cell migration. Stimulation of Normal Human Bronchial Epithelial (NHBE) cells and Calu-3 cells), with a beta2-AR agonist produced a significant increase in time to wound closure compared to untreated control cells. Moreover, agonist stimulated cells were rescued when pretreated with beta-AR antagonists propranolol or ICI-118551. The addition of beta-AR agonists epinephrine or salbutamol to CFTR silenced cells (shCFTR) or cells where CFTR was inhibited with 20uM CFTRinh-172 showed no further decrease in migration rate suggesting that inhibition due to a change in CFTR expression or activity. Furthermore beta-AR agonists reduced lamellipodia protrusion similar to what was observed after CFTR inhibition. Overall these results suggest that treatment of airway epithelial cells with beta-AR agonists causes a decrease in migration rate leading to a significant reduction in the time required for complete wound closure. Additionally these results suggest that stimulating cells with carvedilol causes inhibition of cAMP-stimulated anion secretion by promoting retrieval and internalization of CFTR from the apical membrane. These results signify that the chronic use of beta-AR agonists can lead to increased risk for infection in individuals with obstructive airway disease and the use of bias ligands that promote Gs signaling while blocking beta-arrestin signaling may be the key to effectively treating these patients. These drugs would potentially promote wound repair and mucociliary clearance while limiting the risk of increased exacerbations and infection.
Analysis of the U.S. Department of Agriculture's regulation of genetically engineered crops and reproductive biology of Carex pensylvanica (Lam.)
(2013-08) McGinnis, Esther Ebata
This dissertation is divided into two parts. Chapters 1 through 3 are interdisciplinary and focus on legal and scientific perspectives regarding the regulation of genetically engineered crops. Chapters 4 and 5 evaluated the environmental factors that control flowering in Pennsylvania sedge (Carex pensylvanica Lam.). The commercial potential of genetically engineered (GE) crops has not been fully realized in the United States due to environmental litigation that dramatically affected the pace of GE crop development and deregulation. The USDA's Animal and Plant Health Inspection Service (APHIS) regulates GE crops. However, litigation initiated by nongovernmental organizations exposed APHIS's vulnerability to lawsuits under the National Environmental Policy Act. We concluded in chapters 1 and 2 that APHIS did not adequately evaluate the environmental risks of novel crops, and thus left itself open to litigation. In Chapter 3, we described how the biotechnology industry is attempting to avoid regulation of GE crops through the creation of a non-plant pest loophole.Pennsylvania sedge is an upland forest sedge with horticultural potential as a low maintenance groundcover. For large plantings, achenes are preferred, but Pennsylvania sedge typically produces few achenes in its native habitat. As a first step in improving achene production, Chapter 4 evaluated the effect of vernalization and photoperiod on floral initiation and development. We concluded that Pennsylvania sedge is an obligate short day plant that does not require vernalization for flowering. Plants flowered when exposed to daylengths of 6 to 12 hours. Flowering was completely inhibited with 14-hour photoperiods. Chapter 5 examined the environmental factors that control floral gender sequence and inflorescence culm heights. Plants were found to be determined and florally initiated in the fall in the northern United States. A post-floral induction chilling treatment (winter) was necessary to produce protogynous flowering and normal inflorescence culm elongation.
The dynamic relationship between firm capabilities, regulatory policy, and environmental performance: renewable energy policy and investment in the U.S. electric utility sector.
(2009-09) Fremeth, Adam Ryan
The choice by a firm to improve its environmental performance is a result of both characteristics that distinguish firms from one another and the public policy that compels such action. This dissertation examines how policy outcomes and subsequent firm responses are contingent upon the capabilities of the firms to respond to such policy. I present a theory of compliance specificity that ties firms and regulators together based on the heterogeneity of capabilities that firms hold with regards to a pending public policy of variable stringency. I test this theory within the context of the regulation and investment of renewable power in the U.S. electric utility sector and the growth of a utility scale renewable energy industry. I have identified that firms are able to shape the stringency of an environmental policy in the electric utility sector as the heterogeneity among firms can impact the potential costs that a regulator would face in the case that a policy is set that would leave firms out-of-compliance. Further, the choices that firms make with regards to their use of renewable power is conditioned on the contingent relationships of the capabilities that they possess and these same policies that they have influence over. My theoretical approach and empirical analyses provides a more sophisticated depiction of the interrelationships between firms and regulators within this industry context.
Episode 9: Influence of Occupational Licensing and Regulation
(2017-11-02) Kleiner, Morris; Conners, Kate
In this podcast, Morris Kleiner, professor in labor policy at the Humphrey School of Public Affairs, discusses the policy implications of occupational licensing and regulation in the United States. Occupational licensing has been one of the fastest growing labor market institutions in the United States since World War II. While evidence from the economics literature suggests that licensing has had an important influence on wage determination, benefits, employment, and prices, there are no clear benefits to consumers.
Essays in pharmaceutical economics.
(2010-04) Snider, Julia Thornton
This dissertation is composed of three essays that which examine firms' decisions in developing and marketing prescription drugs and government's role in regulating that process. In the first essay, I look at two forms of promoting prescription drugs and how they interact. Because prescription drugs are chosen by the physician but consumed by the patient, firms have two potential targets for advertising. Advertising to doctors, called "detailing," has historically been more common, but in recent years direct-to-consumer (DTC) advertising has risen in prevalence. The question of how these two types of advertising interact is important for understanding the implications of controversial policies such as the bans on DTC advertising found in most countries. This essay develops an identification strategy exploiting policy differences between the United States and Canada to estimate a model of the joint effects of DTC advertising and detailing. I find a significant complementary effect between the two types: All else equal, for every additional dollar spent on DTC advertising, firms spend eight additional cents on detailing. This implies that DTC advertising bans decrease the effectiveness of detailing, and firms will do less as a result. In the second essay, I examine how advertising can have significant effects on the composition of drug usage between branded and generic drugs. Because generic drugs provide a lower-cost means of delivering drug treatment, such compositional effects are relevant to policymakers facing limited health care budgets. In particular, I focus on the effect of DTC advertising and detailing around the time of patent expiration. I create a model with two firms, one branded and one generic, to capture firms' DTC advertising and detailing decisions over the life of a drug. I compare the model's predictions under different regulations on price and advertising with data from the US and Canada. The model's results are consistent with the empirical observations that detailing and DTC advertising are complementary strategies and that optimal detailing and DTC advertising are lower in an environment where lower prices are set by regulators. In addition, numerical results demonstrate that when consumers are reluctant to switch between the branded drug and the generic, the branded firm may choose to engage in a preemptive advertising campaign prior to patent expiration to limit market share grab by the entering generic or even to delay generic entry. This finding helps explain similar preemptive DTC advertising and detailing campaigns observed in the data. Finally, in the third essay, I analyze the way in which governments optimally balance providing broad access to prescription drugs with creating incentives for innovation. Access and innovation are conflicting goals for price-regulating governments because a low price maximizes access but creates little incentive for innovation. To examine this issue, I model pharmaceutical price regulation as the result of a game between the governments of two countries of varying (economic) size. The agents of the game are a multinational pharmaceutical firm which produces a drug for the global market and the two national governments, each of which is assumed to maximize the welfare of the consumers residing within its borders. Prices are determined as a subgame perfect Nash equilibrium. Observing the two national prices, the firm then undertakes costly innovation to attain a drug quality level which is homogenous across the global market. My model produces the result that dividing the world's population into countries creates a free rider problem in which the public good of pharmaceutical innovation is underfunded. Moreover, whenever one of the two countries is considerably larger than the other, the unique Nash equilibrium is for the smaller country to set its drug price to marginal cost. This suggests that a large economy, such as the United States, will end up providing incentives for drug innovation all over the world.
Essays on market dynamics, regulation and advertising.
(2009-06) Qi, Shi
This dissertation is a collection of three essays that deal with a number of different topics in Industrial Organization. Mainly, they are concerned with market dynamics, regulation policies and advertising. Chapter 1 develops and estimates a dynamic oligopoly model of advertising in the cigarette industry. With this estimated model, I evaluate the impact of the 1971 TV/Radio advertising ban on the cigarette industry. A puzzling fact about this ban is that, while industry advertising spending decreased sharply immediately following its passage, spending then recovered and actually exceeded its pre-ban level within five years. While simple static models cannot account for such a turn of events, the rich dynamic model developed in this paper can. This chapter exploits new previously confidential micro data, now made public through tobacco litigation. In addition, the chapter uses a new concept of Oblivious Equilibrium to handle intractable state space and accelerate equilibrium computation. Chapter 2 studies how advertising influences firms' incentives to invest in R&D. The link between advertising and industry innovation is important, not only because advertising can spur R&D by spreading product knowledge, but also because advertising can discourage new innovative firms from entering the industry. This chapter finds that a worse advertising technology can result in local improvements in industry innovation rates. Globally, however, a complete ban on advertising always reduces industry growth. This result is significant because industry advertising spending is quantitatively significant and there are potential connections between public policy towards advertising and R&D. In chapter 3, we study the performance of the New-Deal sugar manufacturing cartel that existed from 1934 to 1974. We show that the cartel led to major distortions in both how sugar produced at a given factory, and in where the industry was located. The setup of this legal cartel involved four important provisions: sale quotas, land restriction, side payments, and government negotiated factory-farm contracts. We argue that all four provisions distorted how sugar was produced and led to significant loss in productivity measured by sugar recovery rate. Furthermore, we present extensive evidence from industry, company and factory records to support these conclusions.
Essays on the Politics of Innovation
(2023) Park, Michael
The innovation literature has noted that political factors are an important class of determinants for firms’ new technologies (Teece, 1986; Tushman and Rosenkopf, 1992; Ahuja et al., 2013). Accordingly, recent studies have documented the impact of different policies on innovation outcomes (e.g., Arora et al., 2021; Marx et al., 2009; Balsmeier et al., 2017). The works from this stream of literature have mostly studied changes in the regulatory environment which are understood to be exogenous and discontinuous. However, the literature’s focus on this specific type of policy change may be overlooking other political dynamics also important for new technologies. In particular, prior literature suggests that some regulations have a tendency to evolve at a more continuous pace (Hargadon and Douglas, 2001; Weber et al., 2008; Sine and Lee, 2009; Navis and Glynn, 2010), and that firms’ political landscapes can develop endogenously at times (Hillman and Hitt, 1999; Dorobantu et al., 2017; Funk and Hirschman, 2017). Therefore, in this dissertation, I explore how changes in the regulatory environment that are more incremental but commonly-observed can impact the innovation output of firms, and how firms’ attempts to directly shape regulations influence new technologies.
Guardians of Market Integrity: Political Institutions, Regulatory Independence, and Stock Market Development
(2017-03) Lockhart, Lucas
Prior approaches to the politics of stock market development associate consensual political institutions with the stagnation rather than the growth of equity markets. Other research suggests that independent regulatory agencies will almost invariably be captured by industry interests thereby lessening their ability to protect minority shareholders and retail investors. This paper challenges both of these assertions.While politicians do have difficulty credibly committing to investor protection and market integrity, more numerous veto players, proportional elections, and regulatory independence can at least partially ameliorate their credibility problems. Using preexisting measures of political institutions as well as an original dataset of public and private securities market regulatory organizations, I find that consensualism and regulators’ political independence are positively related to stock market size and performance. Furthermore, regulatory independence appears to be especially important for stock market development when consensual political institutions are absent.
The impact of charity and tax law/regulation on not-for-profit news organizations
(The Reuters Institute for the Study of Journalism, University of Oxford and the Information Society Project, Yale Law School, 2016) Picard, Robert; Belair-Gagnon, Valerie; Ranchordás, Sofia
ITS Personal Data Needs: How Much Do We Really Need to Know?
(Intelligent Transportation Systems Institute, Center for Transportation Studies, University of Minnesota, 2012-07) Douma, Frank; Garry, Thomas; Simon, Stephen
The recent spread of geolocation technology in intelligent transportation systems (ITS) raises difficult and important policy questions about locational privacy. However, much of the current public discussion on locational privacy and ITS appears at risk of becoming increasingly disconnected. In one camp are privacy advocates and others who oppose the spread of ITS locational technology on privacy grounds. In the other camp are technologists and the ITS industry who generally view privacy issues as a secondary matter. The net result is that the ITS privacy debate often involves two sides talking past each other, with too little energy spent on finding potential common ground. This disconnect in part results from a lack of basic clarity, on both sides, about just what the needs and interests of those involved in the ITS privacy issue are and how they relate to the betterment of the transportation system. This report sheds new light on the ITS privacy debate by identifying just who is involved in the ITS privacy problem and what their goals are with respect to privacy and ITS data. The analysis identifies the types of locational data and the methods for obtaining it that create privacy conflicts and, in turn, recommends general approaches for both policymakers and industry practitioners to better manage these conflicts. The report represents a first effort in mapping the interests of participants in the ITS privacy debate.
Land Use Practices: Exclusionary Zoning, de Facto or de Jure? An Examination of the Practices of Ten Suburban Communities in the Twin Cities Metropolitan Area.
(Center for Urban and Regional Affairs, University of Minnesota., 1994) Lukermann, Barbara L; Kane, Michael P
Post-translational regulation of mammalian DNA cytidine deaminases.
(2012-06) Demorest, Zachary Lee
Our immune system is faced with the challenge of neutralizing the daily bombardment of invading pathogens. This requires two major response mechanisms in order to achieve this task. The innate immune system acts quickly in response to nonspecific bacterial, viral and nucleic acid based antigens to prevent the onset of disease. In contrast, the adaptive immune system functions slowly but has the added advantage of providing memory and long-term immunity to specific pathogens. Two members of the AID/APOBEC family of cytidine deaminases, APOBEC3G (A3G) and activationinduced deaminase (AID), are critical components of the innate and adaptive immune responses. A3G is a potent inhibitor of Human Immunodeficiency Virus type-1 (HIV-1) as well as a number of other endogenous replicative elements that threaten our genomic integrity. This is accomplished by actively mutating cytosines to uracil in the viral genome during replication. These mutations render the virus non-functional and therefore incapable of spreading infection. AID is necessary for our bodies to generate a diverse antibody repertoire. This is achieved through the initiation of class-switch recombination and somatic hypermutation, processes that allow developing B-cells to generate antibodies of varying isotype with a high specificity for a given antigen. Both of these enzymes, AID and A3G, are DNA mutating enzymes with the potential to wreak havoc on our genome and contribute to cancer. The regulation of these enzymes is multifaceted, involving differential transcription, miRNAs, subcellular localization, interactions with regulatory proteins, and post-translational modifications.
Prescription drug brand Web sites: Guidance where none exists
(University of Minnesota, College of Pharmacy, 2010) Glinert, Lewis
This paper applies insights from linguistics and discourse analysis to prescription drug brand Web sites, with special reference to the 100 top-selling drugs. Such sites give the outward appearance of being a place to go for straightforward information about a specific brand. In reality, they present a confused mix of brand information, health information and hype, muddled organization, and poor indication of authority, creating an imbalance between benefit and risk content. In so doing, they breach the letter and spirit of the regulations governing direct-to-consumer advertising, which the FDA has by default applied to such Web sites but which were not designed for this special type of discourse. The many communicative difficulties proven to be caused by Web sites in general, in particular for the elderly and less literate, also pose ethical problems. A rethinking of the verbal and visual design of these drug sites is needed -- and new regulatory guidance, for which this paper offers recommendations. At stake is not just the quality of health information at brand drug sites but also their credibility.
The safety of farm children and youth: understanding reactions to proposed DOL regulatory changes
(2012-12) Roberts, Megan Luanne
In September 2011, the U.S. Department of Labor (DOL) published its intention to revise child labor regulations for agriculture (RIN: 1235-AA06). The DOL invited public participation through submission of written comments to the Federal Register. Over 10,000 comments were received. Commenting on rulemaking is a key form of public participation, giving interested and affected parties a window of opportunity for voice in the regulation process. This paper is a content analysis of the comments received by the DOL. NVivo software was used to code and classify a random sample of 1000 comments, distinguishing (1) stakeholder groups; (2) key concerns/themes addressed; and (3) degree of support for the proposed changes. The results of the analysis showed a lack of support for the proposal, which corresponds with the DOL's decision to withdraw the proposal in April 2012. A bottom-up participatory approach is a suggested next step to increase buy-in for future children's agricultural safety policy.
Spatial regulation of taxicab services: Measuring empty travel in New York City
(Journal of Transport and Land Use, 2018) King, David A.; Saldarriaga, Juan Francisco
Taxicabs are ubiquitous in cities throughout the world, and the industry is going through regulatory change with the growth of app-based services. In the United States, where taxicabs are typically regulated locally, licenses determine where taxis can pick up passengers. This means that for trips that end outside of licensed boundaries taxicabs are prohibited from picking up passengers and are forced to make “deadhead” return trips. This research estimates empty taxi travel associated with spatial restrictions on passenger trip origins in New York City. In 2012, New York introduced a special taxi category intended to improve taxi access in areas of the city considered underserved by taxicabs. The new green taxicabs, as they are called, can drop off passengers anywhere in the city but are restricted from picking up passengers in the central business districts and at any of the region’s airports. Using detailed trip data for each taxi ride, we estimate that up to 500,000 kilometers per week of deadhead travel are associated with restrictions on pick up locations, and more than 20 percent of all green taxicab trips end in an area where the driver is prohibited from picking up a new passenger.
Three Essays on International Trade and the Environment
(2016-11) Jaeseok, Lee
This dissertation is comprised of three empirical essays on linkage between international trade and the environment. The first essay is about currency exchange rate effects on economic growth and environment through energy consumption and pollution intensive industries trade. The main purpose of this paper is to investigate the impact of the USD exchange rate on real GDP and the CO2 emissions in the United States. The analysis is based on quarterly country-level data on the real trade weighted US dollar index, petroleum consumption, renewable energy consumption, net imports of pollution intensive products, real GDP and CO2 emissions from 1989 to 2015. The result of the Structural Vector Autoregressive (SVAR) model shows that the USD exchange rate is positively related to petroleum consumption, net imports by the United States with major U.S. trading partners in pollution intensive industries, real GDP and CO2 emissions. However, the exchange rate does not have a contemporaneous effect on renewable energy consumption. Moreover, petroleum consumption increases real GDP and domestic CO2 emission levels, while net imports of pollution intensive products decrease real GDP and do not significantly affect CO2 emissions. The second essay is about the effects of stringency of environmental regulations on international trade among OECD member countries. I estimate a gravity equation for bilateral trade with the Heckman two-step model to investigate the impacts of the relative stringency of environmental regulations on bilateral trade flows of energy-intensive commodities and less energy-intensive commodities. Estimated results show that relative difference of environmental regulatory stringency between trading partners has a significant influence on trade flows of energy-intensive commodities, but not on those of less energy-intensive commodities. In addition, we also found that countries import more energy-intensive products from trading partners when the partners’ environmental regulations become weaker. In the final essay, I employ the nested Constant Elasticity of Substitution (CES) model of consumer utility and study how the GMO labeling standards in Korea and Japan affect the trade flows of soybeans and social welfare in these two countries over time. The results show that GMO labeling regulations have a larger impact on GM soybean imports in the short run but, in the long run, the regulations have a greater impact on non-GM soybean imports. We also find that both consumers and producers in these two countries are better off due to the implementation of the GMO labeling regulations.

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