Gary Green - US grants

A cholecystokinin-releasing peptide, termed Luminal CCK-Releasing Factor (LCRF), has been purified from rat intestinal secretions. It has a molecular weight of 8136 daltons, and the sequences has been determined for the N-terminal 41 amino acids. All preliminary studies indicate that LCRF is the important, but elusive factor governing intestinal CCK release. The long term objective of this proposal is to determine the role of this newly discovered peptide in gastrointestinal function. We hypothesize that LCRF is a critical component in the regulation of intestinal cholecystokinin release in the rat. The regulation of LCRF secretion will be investigated in conscious rats with isolated Thiry-Vella Fistulas of jejunum by measuring the effects of nutrients, bile acids and neural blockade on the secretion of immunoreactive LCRF into jejunal loop, and the effect of the luminal environment of the in-continuity proximal intestine (e.g., fed versus fasted state) on LCRF secretion into the jejunal loop. The role of LCRF in pancreatic secretion and CCK release stimulated by dietary protein, trypsin inhibitors, and diversion of bile- pancreatic juice will be investigated using immunoneutralization with anti-sera raised to the biologically active portion of LCRF. The tissue and cellular distribution of LCRF will be investigated using immunohistochemistry and radioimmunoassay (RIA) with antisera raised to selected fragments of the known amino acid sequence of LCRF. All of the major organs associated with regulating gastrointestinal and pancreatic function will be investigated, including the duodenum and ileum, the stomach, the pancreas. Additional studies will test whether LCRF has secretin-releasing activity, based on LCRF-stimulation of a higher/fluid protein ratio of pancreatic secretion compared to CCK-8. These studies are considered critical to the understanding of the tissue distribution of LCRF, to phenotypic identification of the cells producing LCRF, and to understanding the physiology and pathophysiology of LCRF regulation and release. Improved understanding of the mechanisms controlling CCK release is important in diagnosis and treatment of digestive diseases such a pancreatitis, gallbladder disease, gastric emptying abnormalities, colonic dismotility and in food intake regulation.

CCITT is a national consortium of twelve community colleges who are planning for a National Center of Excellence in Advanced Technology Education. Consortium members are: Brevard Community College, FL; Cuyahoga Community College, OH; Foothill College, CA; John C. Calhoun College, AL; Pasadena City College, CA; Pearl River College, MS; Prince George's Community college, MD; Thomas Nelson Community College, VA; and Houston, TX - based Consortium Members San Jacinto Community College, College of the Mainland, Alvin College, and Lee College. These twelve community colleges are linked through their involvement with, and long-term specialized instructional support for nine NASA Field Centers. Linkages are established with area universities and school systems to maximize articulation of technological education programs.The Center is developing plans to establish a national clearinghouse for curricular and faculty development programs as well as educational media supporting these programs to infuse science and mathematics into technological education programs. Curriculum design, faculty enhancement, outreach services, media development and product dissemination activities are being designed to enhance the quality of advanced technological education programs at community colleges and technical institutions nationwide. An advanced national telecommunications and bulletin board delivery system is being established to facilitate cost-effective sharing of information among faculty on a national basis, and to support creative models for distance learning.

DESCRIPTION: The diagnostic and therapeutic modalities available to emergency physicians treating patients with possible myocardial ischemia (MI) are rapidly expanding. Although these therapies offer the potential to decrease morbidity and mortality, their use may also increase costs and expose patients to treatment-related effects. To minimize costs and avoid unnecessary risk of therapy-related complications, treatments must be targeted only to those most likely to gain a benefit. To accomplish this, physicians must be able to rapidly diagnose and risk stratify patients. Increasingly, measurement of laboratory markers of myocardial injury such as myoglobin, CK-MB, and troponins are being utilized for this purpose. Further, a new generation of laboratory assays is being rapidly developed. Rather than detecting cell death, these "markers of coronary thrombosis" will allow direct assessment of the thrombotic state of the patient's coronary arteries at presentation. In the near future, emergency physicians are likely to utilize the new assays along with traditional data sources when making treatment and disposition decisions. No scientifically derived framework exists to aid the physician in interpreting these tests. In addition, the value of these assays for diagnosis or risk stratification has not been systematically studied or directly compared, and no cost-effectiveness studies have been conducted. A predictive instrument able to accurately estimate a patient's probability of MI, as well as the subsequent risk of complications and the need for emergent interventions, would significantly improve the physician s ability to make optimal treatment and disposition decisions. In the proposed study, clinical data and sera from 3,200 patients with possible ischemia presenting to three emergency departments (ED) will be collected, and serum levels of various markers will be measured. The predictive values of the markers, both alone and in combination, will then be determined. Further, by applying statistical techniques to the prospectively collected clinical and laboratory data, a predictive instrument capable of risk stratification of ED patients with possible ischemia will be derived. The ED physician's judgement will then be compared to the potential clinical utility and cost effectiveness of this "comprehensive predictive instrument" for both diagnosis and risk stratification.

drug detection; technology /technique development; blood tests; erythropoietin; urinalysis; biomarker; drug abuse; sample collection; human subject; clinical research;

This project is an exploratory ethnographic study of social and economic transition processes, institutional trajectories, and ideologies of 'development' in and pertaining to rural Alaska. Analyses and opinions relating to the general characters, successes, and failures of the various public (State, Federal) and private (Corporate, NGO) intervention strategies for the purposes of social and economic development will be deduced from informed and/or critically-positioned members of relevant social, economic, and political institutions, including: State legislature, Dept of Labor, Dept of Commerce, Small Business Administration, University of Alaska, Denali Commission, First Alaskans Institute, Alaska Federation of Natives, Native Corporations, Oil Companies, Alaska General Contractors, Institute for Social and Economic Research, and the Alaska Congressional Delegation. This project is both exploratory and preparatory, seeking to compile a series of interconnected models of 1) long-term statewide social and economic processes 2) the trajectories of Alaskan institutions, particularly native tribes and corporations and 3) the topology of ideologies of social and economic development within the state. Data collection takes the form of a kind of ethnographic meta-analysis, wherein the models of social, economic, political, and historical analysis, both formal and informal, of actors are elicited through semi-structured interviews, compared with an eye to their interdependence, then analyzed as a whole. The resulting comprehensive models of significant processes within the state will provide the necessary foundations of knowledge which enable the formulation of more narrowly targeted, in-depth research proposals concerning development in Alaska. The meta-analytic models generated by this research will serve not only to provide the foundations of knowledge for future research and to inform current debates within the fields of rural sociology and the sociology of economic change and development; rural leaders and community members will surely find that the eventual final product of this research both contributes to their knowledge about social and economic conditions in their state and informs debates surrounding the formulation and implementation of local and regional policy.

[unreadable] DESCRIPTION (provided by applicant): The exocrine pancreas produces a large amount (1-2 L/day) of an aqueous secretion containing enzymes and electrolytes. A long-standing paradigm states that the aqueous portion is regulated separately from the enzyme-containing portion, and that the two secretions originate from separate cell types. This is called the two-component hypothesis. One component, the acinar cell, synthesizes and packages the enzymes in zymogen granules, which are discharged into the duct system via exocytosis (called regulated secretion), and the second component, the aqueous component, secreted by the duct cells, dilutes the enzymes with an alkaline solution and the mixture enters the duodenum. The first component, enzymes, is regulated predominately by cholecystokinin and acetylcholine at the acinar cell. The second component, the aqueous, by secretin stimulation of duct cells (in combination with other secretagogues). We propose a modification of this paradigm. In our hypothesis, the acinar cell contributes a substantial volume (equal to duct cells) to the aqueous secretion, and the relationship of the amount of water/electrolyte to the amount of enzyme is tightly regulated. This regulation takes the form of electrolytes (K+, Cl-, HCO3-) entering the zymogen granule and osmotically drawing in water, and causing the granules to swell, often more than doubling their volume. We suggest that this zymogen granule water is the primary secretion of the acinar cell during regulated secretion. At this point, the granule matrix, diluted with water, is discharged into the ductal system where further dilution with ductal secretions occurs. The volume of granule water discharged into the ductal tree by exocytosis can account for all the fluid initially secreted in response to a strong stimulus (neural or hormonal). These steps are well established in many cell types, including the exocrine pancreas. However, their relevance to pancreatic function and disorders have received little attention, in part, we believe, because it represents a major departure from the widely-accepted two-component paradigm, in that it implies that a major fraction of the aqueous component (acinar fluid) and enzyme component are NOT separately regulated, and do NOT originate from separate cell types. This hypothesis has not been tested, because fluid secretion from acinar cells has never been quantified, in contrast to duct fluid, which has been studied in vitro in isolated pancreatic ducts, and in vivo using a rat model in which the acinar cells are completely eliminated but duct cells remain intact and functional. We will use this model, the copper-deficient rat, to test the hypothesis that the hormone, cholecystokinin-58, stimulates a large amount water and protein from the acinar cell, but not from the duct cells, and that this CCK-58 stimulated fluid secretion (but not secretin-stimulated fluid) will be abolished in copper-deficient rats. CCK-58 is unique, because it is the only form in rat blood and the only form that strongly stimulates water and chloride from the pancreas. The results may be highly relevant to the pancreatic disorders pancreatitis and cystic fibrosis. [unreadable] [unreadable] Project narrative: The disorders of the exocrine pancreas, the most important organ for secreting the digestive enzymes, is subject to several disorders, such as cystic fibrosis and pancreatitis. Our study will test a new hypothesis on how the secretions are regulated that may suggest new treatments for these diseases [unreadable] [unreadable] [unreadable] [unreadable]

Gary Paul Green
Michael L. Dougherty
University of Wisconsin-Madison

Guatemala, El Salvador and Honduras sought to integrate into the global economy in the mid 1990s, in part, through foreign direct investment (FDI) in the mineral sector. Spatially incorporating rural communities into the global economy through gold mining has galvanized civic opposition to mining projects in the region. As these anti-mining movements have blossomed across Central America, governments have responded harshly to reassure foreign investors. Ironically, however, as state and civil society determinedly confront each other over the mining issue, this political instability has discouraged foreign investment in other economic sectors. Mining-led market integration has made Central America a less attractive investment environment for the kinds of FDI that best contribute to the economy through job creation, technology and learning spillovers, and linkages with other economic sectors. The prominent literatures on globalization and development?the dependency school, the neoclassical frame, and the developmentalist state literature, do not account for the emergence of this paradox. Instead, these cases may constitute the emergence of a new model of mineral-led market integration in the neoliberal era, where relationships between states, firms and communities are reconfigured. Incorporating political process theory to frame civic opposition, public choice theory to frame state intervention, and a commodity chain analysis of the global gold mining industry may help illuminate this reconfiguration. To explore the stand-off between state and civil society at the core of this development paradox, this dissertation poses two research questions: 1) how do rural communities make sense of their integration into the global economy through gold mining? And 2) how do these governments negotiate their social contractual obligations to civil society with their contractual obligations to foreign capital? Data collection will involve twelve months of ethnographic fieldwork in rural communities in these three nations, as well as interviews with key informants in government, the mining sector, and civic society. This research advances discovery and sociological knowledge by probing the limits of the ?grand theories? of development and globalization in the context of current restructuring in the global gold industry, the growth of transnational and national social movements, and the political parameters of neoliberal foreign direct investment policies. The results of this research will be disseminated through university courses, public lectures, and Spanish-language publications facilitated by IARNA.

SES-1334870)
Gary Paul Green
Yifei Li
University of Wisconsin-Madison

Environmental protection has become a core area of policy intervention for governments across the world. Sociological research in the past few decades articulated the process by which increasing public awareness of environmental issues led to environmental policy-making. The rise of environmental movements, as well as many other forms of democratic expression of environmental attitudes, shaped the extent to which governments commit resources to protect the natural environment. Existing research emphasizes the relationship between the power of popular environmentalism and the capacity of state agencies to protect the environment. These existing theories presume the existence of democratic institutional arrangements. In the absence of democracy, how is the emergence of environmental governance explained? What motivation does an authoritarian governmental structure offer for the local state to engage in environmental protection? Sociological theories provide two hypotheses. First, past research found that in the authoritarian context, the local state tends to be highly responsive to mandates from the central regime. It seems likely that some cities have strong environmental protection programs because of tighter bureaucratic connection to the central state. Second, scholars have noted the unique mechanism of government accountability in the absence of voting power. They point to informal channels of public expression as a bridge between the public and the state. It therefore also seems plausible that cities commit to environmental protection because of strong local expression of environmentalism through informal means. To answer these questions, this dissertation research will collect archival data from four Chinese cities. Structured comparisons between the historical evolutions of local state intervention in environmental protection in these cities to identify the political mechanisms that gave rise to local environmental governance. Research findings will contribute to an explanatory theory of the local environmental state that is sensitive to political structuring from above, as well as public sentiments from below.

Broader Impacts

Environmental protection is a central problem in international development. Global efforts to combat climate change will not succeed without effectively engaging the most populated country in the world. The hundreds of international environmental organizations currently operating in the country testify to the importance of China in the global enterprise of sustainability. This dissertation will supply important knowledge about the working of the Chinese state and its propensity to commit to, and act in accordance with, environmental protection goals. The co-PI will provide summaries of best practices of environmental protection policies for educators, environmental advocacy groups, and policy-makers. Public data obtained during fieldwork will also be shared with interested parties to contribute to future studies into environmental protection in China and elsewhere.

How do neighborhood residents experience social isolation and socioeconomic diversity in gentrifying neighborhoods? Studies of neighborhoods have historically explored socioeconomic diversity between segregated and homogeneous neighborhoods, finding local context impacts individual outcomes, such as educational attainment. However, gentrifying cities are experiencing an increase in density and population change, such that diversity is increasing within neighborhoods. This dissertation examines how access to and use of local resources changes for residents as population and neighborhood context gentrify.

Using place-based interviews paired with geo-spatial data on daily mobility patterns conducted in the gentrifying neighborhood of Crown Heights, Brooklyn I explore how socioeconomic diversity is constructed and experienced by residents, specifically asking: (1) how do residents perceive and negotiate access to and ownership over local resources, such as grocery stores and health services? (2) How do perceptions of access and ownership intersect with tenure, race, class, gender, and age status of residents? and (3) How does this access to local resources impact material inequality and daily travel time? The gentrification of American cities is producing growing socioeconomic diversity in places that have formerly been much more homogeneous, and this project seeks to understand how that diversity is experienced and dealt with at the local level.

A 2019 National Science Board report stressed the critical need for an exceptional skilled technical workforce to ensure the success of the nation's science- and engineering-driven industries. This project will serve the national interest by preparing skilled technical workers in regenerative medicine, an emerging field that aims to repair, regrow, or replace damaged cells, organs, and tissues. Regenerative medicine is a cross-disciplinary field of biotechnology and bioengineering that includes convergent technologies such as nanotechnology, artificial intelligence and machine learning, mechanical engineering technologies, data science, and cyberbiosecurity. Regenerative medicine is rapidly evolving from basic research and development stages, through clinical translation and into biomanufacturing. A significant gap in availability of skilled technicians in regenerative medicine biomanufacturing has been defined by identifying the required skills and the extent of the skills gap. To help fill this need, Wake Forest Institute for Regenerative Medicine is partnering with Forsyth Technical Community College, Simon G. Atkins High School, regional Historically Black Colleges and Universities, employers, and professional and trades organizations. This partnership intends to bring the new science and technology of regenerative medicine into the community college sector to ensure the nation prepares the needed regenerative medicine technicians.

The project intends to meet this goal by developing a regional model for education of skilled technicians in regenerative medicine biomanufacturing. Specifically, it will develop and deliver faculty professional development in regenerative medicine, from the high school level through community college and university levels (through articulated programs). It will also disseminate research-based knowledge, skills, and abilities for the regenerative medicine field to community colleges and their partners. Finally, the project will develop multiple career entry options and pathways for community college-prepared technicians and incumbent employees, with a focus on serving people from communities that are underrepresented in STEM. The project builds upon recent NSF-sponsored Advanced Technology Education efforts, which have provided the scientific, technical, and educational foundation for this project. The project team plans to work with diverse teams of experts enabling development and production of replacement cells and organs and the expansion of cells for therapy. This project is funded by the Advanced Technological Education program that focuses on the education technicians for the advanced-technology fields that drive the nation's economy.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.