Salmeterol enhances the cardiac response to gene therapy in Pompe disease.

Enzyme replacement therapy (ERT) with recombinant human (rh) acid α-glucosidase (GAA) has prolonged the survival of patients. However, the paucity of cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, where it is needed to take up rhGAA, correlated with a poor response to ERT by muscle in Pompe disease. Clenbuterol, a selective β2 receptor agonist, enhanced the CI-MPR expression in striated muscle through Igf-1 mediated muscle hypertrophy, which correlated with increased CI-MPR (also the Igf-2 receptor) expression. In this study we have evaluated 4 new drugs in GAA knockout (KO) mice in combination with an adeno-associated virus (AAV) vector encoding human GAA, 3 alternative β2 agonists and dehydroepiandrosterone (DHEA). Mice were injected with AAV2/9-CBhGAA (1E+11 vector particles) at a dose that was not effective at clearing glycogen storage from the heart. Heart GAA activity was significantly increased by either salmeterol (p<0.01) or DHEA (p<0.05), in comparison with untreated mice. Furthermore, glycogen content was reduced in the heart by treatment with DHEA (p<0.001), salmeterol (p<0.05), formoterol (p<0.01), or clenbuterol (p<0.01) in combination with the AAV vector, in comparison with untreated GAA-KO mice. Wirehang testing revealed that salmeterol and the AAV vector significantly increased performance, in comparison with the AAV vector alone (p<0.001). Similarly, salmeterol with the vector increased performance significantly more than any of the other drugs. The most effective individual drugs had no significant effect in absence of vector, in comparison with untreated mice. Thus, salmeterol should be further developed as adjunctive therapy in combination with either ERT or gene therapy for Pompe disease.

Information Interventions to Reduce Maternal Mortality in Indonesia

Indonesia consistently records higher levels of maternal mortality than other countries in Southeast Asia with its same level of socioeconomic development. I use a quasi-experimental, difference-in-differences approach to understand whether the role of information on the risk of death in childbirth can change women’s reproductive behaviors. In the first two chapters, I use the Maternal Mortality Module from the Demographic and Health Survey (DHS) in Indonesia to examine fertility and reproductive behavior responses to a sister’s death in childbirth. Fertility desires remain relatively unchanged but women take up behaviors in subsequent births that avert the risk of maternal death. In the last chapter, I combine population-representative data from the DHS with a village-level census (PODES) on service availability to understand how a village-level intervention to improve obstetric service use using a birth preparedness and complications readiness (BPCR) approach may improve obstetric service use. In this study, I find that the Desa Siaga intervention in Indonesia improved knowledge of the danger signs of complications among women but not among men relative to villages that did not get the program while controlling for endogenous program placement. More women got antenatal care due to the program but use of a skilled birth attendant and postpartum care did not change as a result of the intervention. Both genders report discussing a blood donor in preparation for delivery.

Creative Destruction: Towards a Theology of Institutions

A theology of institutions is dependent upon an imagination sparked by the cross and shaped by the hope of the resurrection. Creative destruction is the institutional process of dying so that new life might flourish for the sake of others. Relying upon the institutional imagination of James K.A. Smith, the institutional particularity of David Fitch, and L. Gregory Jones’ traditioned innovation, creative destruction becomes a means of institutional discipleship. When an institution practices creative destruction, it learns to remember, imagine, and be present so that it might cultivate habits of faithful innovation. As institutions learn to take up their cross a clearer telos comes into view and collaboration across various organizations becomes possible for a greater good. Institutions that take up the practice of creative destruction can reimagine, reset, restart or resurrect themselves through a kind of dying so that new life can emerge. Creative destruction is an apologetic for an institutional way of being-in-the-world for the sake of all beings-in-the-world.

Knowing The Way: Scriptural Imagination and the Acts of the Apostles

In this dissertation, I offer a pedagogical proposal for learning the Christian Scriptures guided by respect for the nature of the reader and the integrity of the biblical text. Christian educators have profitably developed recent theoretical interest in the body’s role in human meaning with regard to worship and praxis methodologies, but the implications of this research for communal study of the biblical text merit further development. I make the case for adopting scriptural imagination as the goal of pedagogically constructed encounters with the Christian Scriptures. The argument proceeds through a series of questions addressing both sides of the text/reader encounter.

Chapter one considers the question “what is the nature of the reader and, subsequently, the shape of the reader’s ways of knowing?” This investigation into recent literature on the body’s involvement in human knowing includes related epistemological shifts with Christian education. On the basis of this survey, imagination emerges as a compelling designator of an incorporative, constructive creaturely capacity that gives rise to a way of being in the world. Teachers of Scripture who intend to participate in Christian formation should account for the imagination’s centrality for all knowing. After briefly situating this proposal within a theological account of creatureliness, I make the initial case for Scriptural imagination as a pedagogical aim.

Imagination as creaturely capacity addresses the first guiding value, but does this proposal also respect the integrity and nature of the biblical text, and specifically of biblical narratives? In response, in chapter two I take up the Acts of the Apostles as a potential test case and exemplar for the dynamics pertinent to the formation of imagination. Drawing on secondary literature on the genre and literary features of Acts, I conclude that Acts coheres with this project’s explicit interest in imagination as a central component of the process of Christian formation in relationship to the Scriptures.

Chapters three and four each take up a pericope from Acts to assess whether the theoretical perspectives developed in prior chapters generate any interpretive payoff. In each of these chapters, a particular story within Acts functions as a test case for readings of biblical narratives guided by a concern for scriptural imagination. Each of these chapters begins with further theoretical development of some element of imaginal formation. Chapter three provides a theoretical account of practices as they relate to imagination, bringing that theory into conversation with Peter’s engagement in hospitality practices with Cornelius in Acts 10:1-11:18. Chapter four discusses the formative power of narratives, with implications for the analysis of Paul’s shipwreck in Acts 27:1-28:16.

In the final chapter, I offer a two-part constructive pedagogical proposal for reading scriptural narratives in Christian communities. First, I suggest adopting resonance above relevance as the goal of pedagogically constructed encounters with the Scriptures. Second, I offer three ways of reading with the body, including the physical, ecclesial, and social bodies that shape all learning. I conclude by identifying the importance of scriptural imagination for Christian formation and witness in the twenty-first century.

Capacity Investment in Renewable and Conventional Energy Sources

This dissertation studies capacity investments in energy sources, with a focus on renewable technologies, such as solar and wind energy. We develop analytical models to provide insights for policymakers and use real data from the state of Texas to corroborate our findings.

We first take a strategic perspective and focus on electricity pricing policies. Specifically, we investigate the capacity investments of a utility firm in renewable and conventional energy sources under flat and peak pricing policies. We consider generation patterns and intermittency of solar and wind energy in relation to the electricity demand throughout a day. We find that flat pricing leads to a higher investment level for solar energy and it can still lead to more investments in wind energy if considerable amount of wind energy is generated throughout the day.

In the second essay, we complement the first one by focusing on the problem of matching supply with demand in every operating period (e.g., every five minutes) from the perspective of a utility firm. We study the interaction between renewable and conventional sources with different levels of operational flexibility, i.e., the possibility

of quickly ramping energy output up or down. We show that operational flexibility determines these interactions: renewable and inflexible sources (e.g., nuclear energy) are substitutes, whereas renewable and flexible sources (e.g., natural gas) are complements.

In the final essay, rather than the capacity investments of the utility firms, we focus on the capacity investments of households in rooftop solar panels. We investigate whether or not these investments may cause a utility death spiral effect, which is a vicious circle of increased solar adoption and higher electricity prices. We observe that the current rate-of-return regulation may lead to a death spiral for utility firms. We show that one way to reverse the spiral effect is to allow the utility firms to maximize their profits by determining electricity prices.