Role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in IL-10-deficient mice.

BACKGROUND: Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il10(-/-) mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il10(-/-) mice to the development of spontaneous colitis and resulted in increased intestinal permeability in vivo that preceded the development of colon inflammation. However, mast cell deficiency did not affect the severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affect intestinal permeability. CONCLUSIONS/SIGNIFICANCE: Mast cells thus appear to have a primarily protective role within the colonic microenvironment by enhancing the efficacy of the mucosal barrier. In addition, although mast cells were previously implicated in progression of sporadic colon cancers, mast cells did not affect the incidence or severity of colonic neoplasia in this inflammation-associated model.

American Manna: Religious Responses to the American Industrial Food System

“American Manna: Religious Responses to the American Industrial Food System” is an investigation of the religious complexity present in religious food reform movements. I conducted ethnographic fieldwork at four field sites. These field sites are a Jewish organic vegetable farm where the farmers begin their days with meditation, a Christian raw vegan diet center run by Messianic Jews, a Christian family that raises their cattle on pastures and sends them to a halal processing plant for slaughter, and a Jewish farm where Christian and Buddhist farm staff helped to implement shmita, the biblical agricultural sabbatical year.

The religious people of America do not exist in neatly bound silos, so in my research I move with the religious people to the spaces that are less clearly defined as “Christian” or “Jewish.” I study religious food reformers within the framework of what I have termed “free-range religion” because they organize in groups outside the traditional religious organizational structures. My argument regarding free-range religion has three parts. I show that (1) perceived injustices within the American industrial food system have motivated some religious people to take action; (2) that when they do, they direct their efforts against the American food industry, and tend to do so outside traditional religious institutions; and finally, (3) in creating alternatives to the American food industry, religious people engage in inter-religious and extra-religious activism.

Chapter 1 serves as the introduction, literature review, and methodology overview. Chapter 2 focuses on the food-centered Judaism at the Adamah Environmental Fellowship at the Isabella Freedman Jewish Retreat Center in Falls Village, CT. In Chapter 3, I discuss the Hallelujah Diet as prescriptive literature and as it is put into practice at the Hallelujah Diet Retreat Center in Lake Lure, NC. Chapter 4 follows cows as they move from the grassy hills of Baldwin Family Farms in Yanceyville, NC to the meat counter at Whole Foods Markets. In Chapter 5, I consider the shmita year, the biblical agricultural sabbatical practice that was reimagined and implemented at Pearlstone Center in Baltimore, MD during 2014-2015. Chapter 6 will conclude this dissertation with a discussion of where religious food reform has been, where it is now, and a glimpse of what the future holds.

Robust Uncertainty Quantification and Scalable Computation for Computer Models with Massive Output

Uncertainty quantification (UQ) is both an old and new concept. The current novelty lies in the interactions and synthesis of mathematical models, computer experiments, statistics, field/real experiments, and probability theory, with a particular emphasize on the large-scale simulations by computer models. The challenges not only come from the complication of scientific questions, but also from the size of the information. It is the focus in this thesis to provide statistical models that are scalable to massive data produced in computer experiments and real experiments, through fast and robust statistical inference.

Chapter 2 provides a practical approach for simultaneously emulating/approximating massive number of functions, with the application on hazard quantification of Soufri\`{e}re Hills volcano in Montserrate island. Chapter 3 discusses another problem with massive data, in which the number of observations of a function is large. An exact algorithm that is linear in time is developed for the problem of interpolation of Methylation levels. Chapter 4 and Chapter 5 are both about the robust inference of the models. Chapter 4 provides a new criteria robustness parameter estimation criteria and several ways of inference have been shown to satisfy such criteria. Chapter 5 develops a new prior that satisfies some more criteria and is thus proposed to use in practice.