Jung Hwan Kim, MD, Pusan National University, Korea - US grants

Our purpose here is to further evaluate the influence of host genetics on CJD disease. Specifically, incubation time, pathological sequelae (morphological and biochemical) and host genetic markers will be evaluated. Two major models are proposed for these studies: 1) CJD in various inbred strains of hamsters and 2) mouse inbred strains that show destructive white matter lesions.

North Carolina A&T State University, in collaboration with UNC Charlotte, is continuing and expanding the SFS Cyber Corps program established over the last three years. During the initial program period, UNC Charlotte and NC A&T State University have produced 33 high quality skilled Information Assurance (IA) professionals with a cumulative enrollment of 68 students consisting of 49% African American and 32% women.

Intellectual Merit. The UNC Charlotte/NC A&T SFS program has a well-balanced curriculum that is matching well with the human resource needs of the federal government. It is benefiting from a distinguished faculty and a vibrant and well-funded IA research program. To enhance student learning, the program is building on several innovative features including IA certificates students are earning in conjunction with their B.S., B.A., M.S. or Ph.D. degrees in Information Technology, Computer Science, or Software and Information Systems; research projects, and experiential learning activities. Students are developing a strong commitment to community service through participation in community service activities, and program alumni are serving as mentors to current SFS students to aid in student placement efforts.

Broader Impact. The UNC Charlotte/NC A&T SFS program is helping to address the national need for qualified information technology professionals trained in information assurance and computer security in areas of research and development (in both technology and policy areas), operations, as well as project management. In order to increase the diversity of IA professionals in the federal workforce, the UNC Charlotte/NC A&T SFS program is placing special emphasis on recruiting and graduating highly talented students from underrepresented groups. For many years, NC A&T State University has been a recognized world-leader in producing high quality African-American engineers. It has a very well established mechanism to attract talented minority students from all over the U.S. and a very well developed mentoring and support system to help them succeed, both academically as well as in job placement. NC A&T is a favored recruitment destination for many federal agencies, an important advantage to help place SFS graduates in federal services.

Differential equations are mathematical descriptions useful for modeling dynamic phenomena. Problems such as describing fluid flow, the spread of a disease, and stock option prices are often solved by appealing to differential equations. When students of science and engineering learn the techniques of differential equations it can be difficult for them to move from technical, symbolic mathematical manipulations to a more qualitative, conceptual understanding. This project investigates how to tutor students in such conceptual understanding. It will study the techniques and pedagogical knowledge employed by expert tutors and try to teach these techniques to less experienced peer tutors. It will develop new tests to measure how well students comprehend differential equations on a conceptual level and study the efficacy of various tutorial methods. And it will investigate how to build software for computer-assisted tutoring of differential equations, where a computer follows the conversation and suggests some of the expert methods to the inexperienced tutor.

DESCRIPTION (provided by applicant): Obesity has reached an epidemic stage and created serious public health problems in the United States. Genetic factors are strongly involved in the development of obesity, most likely in the form of interactions of multiple genes with obesity-promoting environments, such as high fat diets. The present proposal focuses on the identification of pathophysiological mechanisms that could point to the cause of obesity mediated by an obesity susceptibility locus, tabw2, and its molecular basis which is responsible for fat mass accretion that is exaggerated by feeding high fat diets. Previously, we have mapped a quantitative trait locus (QTL) linked to body weight on mouse chromosome 6 in a cross between C57BL/6J (B6) and obese diabetic TALLYHO/JngJ (TH) mouse strains. The TH allele was associated with higher body weights, and the QTL is named tabw2 (TALLYHO Associated Body Weight 2). Subsequently, we have constructed a congenic strain that carries a TH-derived genomic segment containing tabw2 on a B6 background. This congenic strain of mice (tabw2 mice) exhibits increased adiposity, hyperleptinemia, hypertrophied adipocytes, increased lipogenesis, and dampened diurnal rhythms of circulating leptin levels. Upon high fat diet feeding, the obesity in tabw2 mice becomes exacerbated, followed by developing insulin resistance. Based on our preliminary data, we hypothesize that a TH allelic difference at tabw2 locus confers susceptibility to obesity that is magnified by high fat diets. In order to test this hypothesis we propose the following specific aims: Aim 1, investigate mechanisms of energy partitioning in tabw2 mediated obesity on low- and high-fat diets;Aim 2, fine map the tabw2 interval using nested recombinant subcongenic lines and haplotype mapping;Aim 3, identify the molecular basis of the tabw2 gene(s). At the successful conclusion of this work, the pathogenic mechanisms leading to an excess fat mass mediated by the tabw2 mutation(s) and the potential role of dietary fat in the development and progression of the condition will be elucidated. We will have identified the tabw2 gene(s) which when mutated causes obesity that is exacerbated by high fat diets. This study will thereby potentially provide new targets for intervention of human obesity. PUBLIC HEALTH RELEVANCE: Obesity has reached an epidemic stage and created serious public health problems in the United States. Genetic factors are strongly involved in the development of obesity, most likely in the form of interactions of multiple genes with obesity-promoting environments, such as high fat diets. Knowing the metabolic mechanism and molecular basis underlying the obesity associated with the susceptibility gene, tabw2 in mice, which we propose in this study, will provide new insights regarding obesity genes and pathways that could be tested in humans.

Computer Science (31)

This collaborative project provides scholarships for students seeking degrees (either undergraduate or graduate) in Information Assurance (IA) at the two collaborating institutions. Each scholarship is for the last two years of a student's degree program. Scholarship students engage in rigorous academic programs that emphasize both theory and practice of IA and that incorporate research and experiential learning. Upon graduation, scholarship recipients must work for a Federal government agency in an IA position.

The scholarship program helps to address the nation's need for qualified information technology professionals working in government agencies. This collaborating institution is an HBCU that has a well-established mechanism to attract talented minority students into its IA program and to help them succeed as IA professionals.

The S-STEM Program for Computer Science Recruitment, Retention and Research (CS3R) recruits and provides scholarships for 16 undergraduate students and 12 graduate students who are academically talented and financially needy. Through a wide range of support structures and resources, as well as the leadership of an experienced management team, the project is ensuring that scholarship recipients receive all crucial support necessary to achieve success in the computer science discipline. The S-STEM CS3R project recruits S-STEM student candidates using a variety of approaches targeting underrepresented African American students. To help the S-STEM scholars to succeed, comprehensive mentoring services are provided, including faculty mentors, peer mentors, and alumni mentors. The educational plans and academic performance of the S-STEM scholars are closely monitored in order to retain them in the scholarship program. The S-STEM CS3R project also involves the S-STEM scholars in the various research programs in the department to integrate research into education, and to develop the students' research capabilities. To build the S-STEM community, the project includes such activities as welcome receptions, monthly seminars and an end-of-semester picnic. The S-STEM CS3R project increases the industrial experience opportunities for the scholarship recipients and increases their leadership potential through fostering habits of involvement.

The project's significance and importance lie in its focus on addressing both the motivational aspects and conceptual learning barriers for students in early computer programming courses. In these courses the concepts become difficult with many computer science oriented students stalling in their college career. The project will apply modern ideas of group exercises in a highly interactive chat-room environment, where students will be accountable for helping each other and individually accountable for learning. The project's system will record and will then apply text analytics to student group interactions, summarizing for the instructor how well the student groups are functioning both socially and in problem solving.

The goals and scope of the project are to develop new collaboration assignments that exercise Java programming language analytic and conceptual skills. At the same time the project will study how students engage with the exercises and how student enthusiasm can be increased. These studies underlie further development of the text classifier technology to monitor for cognitive, affective, and linguistic phenomena that are indicative of enthusiastic students actively discussing and learning. Some measurements, for example, whether the students evince enthusiasm, should be usable in a wide variety of other pedagogical domains. The project will assess how well this intervention succeeds in keeping students motivated, both within individual exercises and in their student careers.

Project Summary The global prevalence of Type 2 diabetes (T2D) is a major health concern. There is strong evidence of a genetic basis for human T2D, which follows a polygenic pattern of inheritance. Epidemiological and experimental data suggest that T2D arises from the interplay between genetics and environment (e.g., diet), partly explaining the current diabetes epidemic in a Western environment of excessive energy- dense food consumption. Despite this evidence, the exact nature of gene-diet interactions and underlying causal mechanisms are poorly understood in T2D. One major reason originates from difficulties in accurate dietary assessment in humans, partly due to unreliable methodology such as dietary recalls and questionnaires and individual's subjective perception about food intake. One approach to address this complexity is to use animal models, where the environment can be carefully controlled and modified. TALLYHO (TH) mice encompass many aspects of polygenic human T2D. Our preliminary studies demonstrated that the penetrance of genetic susceptibility to T2D is modulated in TH mice by nutritionally modified diets. Therefore, we hypothesize that (1) the susceptibility of TH mice to T2D is modulated by the combined interaction of diet and genetics which act to alter gene expression in selected tissues and (2) identification of genes whose expression varies with this interaction will enable us to identify T2D susceptibility genetic variants in the TH mouse. To test these hypotheses we will: (1) investigate chronological development of insulin resistance and impairment of insulin secretion in response to diabetogenic diets in TH mice and (2) characterize global gene expression changes caused by diabetogenic diets in TH vs. B6 and F1(FVBxB6) mice and identify the associated genetic variants and pathways by using an integrated functional genomics approach. These studies will identify molecular predictors that connect diet with the etiology of T2D. !