Lake Monroe Diagnostic And Feasibility Study

This diagnostic and feasiblity has two primary purposes: (1) to diagnose problems with Lake Monroe and (2) identify technically feasible solutions to the problems identified. The protocol used to conduct this study is specified in guidance materials provided by the U.S. Environmental Protection Agency.Prepared for: Monroe County Commissioners, Courthouse Room 302, Bloomington, IN 4740

MYC Overexpression Induces Prostatic Intraepithelial Neoplasia and Loss of Nkx3.1 in Mouse Luminal Epithelial Cells

Lo-MYC and Hi-MYC mice develop prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma as a result of MYC overexpression in the mouse prostate[1]. However, prior studies have not determined precisely when, and in which cell types, MYC is induced. Using immunohistochemistry (IHC) to localize MYC expression in Lo-MYC transgenic mice, we show that morphological and molecular alterations characteristic of high grade PIN arise in luminal epithelial cells as soon as MYC overexpression is detected. These changes include increased nuclear and nucleolar size and large scale chromatin remodeling. Mouse PIN cells retained a columnar architecture and abundant cytoplasm and appeared as either a single layer of neoplastic cells or as pseudo-stratified/multilayered structures with open glandular lumina—features highly analogous to human high grade PIN. Also using IHC, we show that the onset of MYC overexpression and PIN development coincided precisely with decreased expression of the homeodomain transcription factor and tumor suppressor, Nkx3.1. Virtually all normal appearing prostate luminal cells expressed high levels of Nkx3.1, but all cells expressing MYC in PIN lesions showed marked reductions in Nkx3.1, implicating MYC as a key factor that represses Nkx3.1 in PIN lesions. To determine the effects of less pronounced overexpression of MYC we generated a new line of mice expressing MYC in the prostate under the transcriptional control of the mouse Nkx3.1 control region. These “Super-Lo-MYC” mice also developed PIN, albeit a less aggressive form. We also identified a histologically defined intermediate step in the progression of mouse PIN into invasive adenocarcinoma. These lesions are characterized by a loss of cell polarity, multi-layering, and cribriform formation, and by a “paradoxical” increase in Nkx3.1 protein. Similar histopathological changes occurred in Hi-MYC mice, albeit with accelerated kinetics. Our results using IHC provide novel insights that support the contention that MYC overexpression is sufficient to transform prostate luminal epithelial cells into PIN cells in vivo. We also identified a novel histopathologically identifiable intermediate step prior to invasion that should facilitate studies of molecular pathway alterations occurring during early progression of prostatic adenocarcinomas

Think 500, not 50! A scalable approach to student success in STEM

Abstract Background UMBC, a diverse public research university, “builds” upon its reputation in producing highly capable undergraduate scholars to create a comprehensive new model, STEM BUILD at UMBC. This program is designed to help more students develop the skills, experience and motivation to excel in science, technology, engineering, and mathematics (STEM). This article provides an in-depth description of STEM BUILD at UMBC and provides the context of this initiative within UMBC’s vision and mission. Key highlights The STEM BUILD model targets promising STEM students who enter as freshmen or transfer students and do not qualify for significant university or other scholarship support. Of primary importance to this initiative are capacity, scalability, and institutional sustainability, as we distill the advantages and opportunities of UMBC’s successful scholars programs and expand their application to more students. The general approach is to infuse the mentoring and training process into the fabric of the undergraduate experience while fostering community, scientific identity, and resilience. At the heart of STEM BUILD at UMBC is the development of BUILD Group Research (BGR), a sequence of experiences designed to overcome the challenges that undergraduates without programmatic support often encounter (e.g., limited internship opportunities, mentorships, and research positions for which top STEM students are favored). BUILD Training Program (BTP) Trainees serve as pioneers in this initiative, which is potentially a national model for universities as they address the call to retain and graduate more students in STEM disciplines – especially those from underrepresented groups. As such, BTP is a research study using random assignment trial methodology that focuses on the scalability and eventual incorporation of successful measures into the traditional format of the academy. Implications Critical measures to transform institutional culture include establishing an extensive STEM Living and Learning Community to increase undergraduate retention, expanding the adoption of “active learning” pedagogies to increase the efficiency of learning, and developing programs to train researchers to effectively mentor a greater portion of the student population. The overarching goal of STEM BUILD at UMBC is to retain students in STEM majors and better prepare them for post baccalaureate, graduate, or professional programs as well as careers in biomedical and behavioral research