Novel Roles of the E2F-2 Transcription Factor and Regulation of Cyclin E in Promoting Terminal Erythroid Maturation

Swartz, Kelsey Northwestern University 2016 해외박사(DDOD)

ABSTRACT Novel Roles of the E2F-2 Transcription Factor and Regulation of Cyclin E in Promoting Terminal Erythroid Maturation Kelsey L Swartz E2F-2 is a Retinoblastoma (Rb)-regulated transcription factor induced during terminal erythroid maturation. Cyclin E-mediated Rb hyper-phosphorylation induces E2F transcriptional activator functions. E2F-2-loss causes reduced peripheral red blood cell (RBC) counts, without altering relative abundances of erythroblast subpopulations. To determine how E2F-2 regulates RBC production, we comprehensively studied erythropoiesis using knockout mice and hematopoietic progenitors. We found that efficient stress erythropoiesis in vivo requires E2F-2 and also identified an unappreciated role for E2F-2 in erythroblast enucleation. In particular, E2F-2 deletion impairs nuclear condensation, a morphologic feature of enucleating erythroblasts. Transcriptome profiling of E2F-2 null, mature erythroblasts demonstrated widespread changes in gene expression. Notably, we identified Citron Rho-interacting kinase (CRIK), which has known functions in mitosis and cytokinesis, as induced in erythroblasts in an E2F-2-dependent manner, and we found CRIK activity promotes efficient erythroblast enucleation and nuclear condensation. Together, our data reveal novel, lineage-specific functions for E2F-2 and suggest that some mitotic kinases have additional, specialized roles supporting enucleation of maturing erythroblasts. We previously reported that deregulated cyclin E activity causes defective terminal maturation of nucleated erythroblasts in a knock-in mouse model in which Fbw7-mediated ubiquitination and degradation is ablated. Here, we detailed the consequences of deregulating cyclin E in bone marrow erythroid cells during terminal maturation in vivo. We found that disruption of Fbw7-mediated degradation of cyclin E impairs terminal erythroid differentiation at a discrete stage before enucleation. We also found that normal regulation of cyclin E restrains accumulation of reactive oxygen species (ROS) and expression of genes that promote mitochondrial biogenesis in differentiating cells. Notably, we find maturation defects and elevated ROS associated with deregulated cyclin E is normalized by E2F-2 deletion. Finally, stabilized cyclin E and ROS accumulation induces hyper-methylation at histone 3 lysine 9, disrupting normal transcriptional components of terminal maturation. Thus, regulation of cyclin E is linked to metabolism and gene expression during terminal maturation.

Native American autoethnography, sovereignty, and self: Tribal knowledges in new genres (Zitkala-Sa, Charles Eastman, Luther Standing Bear, Helen Sekaquaptewa, Edmund Nequatewa)

Kelsey, Penelope Myrtle University of Minnesota 2002 해외박사(DDOD)

My dissertation is a comparative study of early autobiographies by Dakota and Hopi authors, including Zitkala-Ša, Charles Eastman, Luther Standing Bear, Helen Sekaquaptewa, and Edmund Nequatewa. My framework is composed of new and old epistemologies, from oral traditional norms of narration to the poststructuralist writing of Anishinaabe theorist Gerald Vizenor. When these works have received attention in the past (i.e., Zitkala-Ša, Eastman), scholars invariably have argued that these authors view the American Indian situation as hopeless: they are tragic mixed-bloods whose literary role is to usher in the new era of Anglo dominance. In contrast, I argue that these narrators <italic>do</italic> have tribally-centered agendas, and our understanding of sovereignty in the nineteenth and twentieth centuries benefits from considering how they push these agendas. Thus, one of my major objectives is an examination of how these authors create new representations of American Indians and how they seek to influence their readership's understanding of U.S./Indian policy. I consider how they stand as representatives of their nations, whether or not they present themselves in that light, how they create themselves as gendered and classed figures, how they portray family and tribe, and how they use the colonizer's and the tribe's tools in writing their own autoethnography. An important part of my project is tracing the authors' use of tribal forms of self-narration, both traditional and syncretic, literary and material-cultural, for these generic influences have been largely ignored. I seek to answer the following questions in my thesis: What sorts of narrative conventions do the authors deploy from tribal and Euroamerican traditions? How do they use them to further a tribally-centered agenda? How are sovereignty and self-determination positioned in the narrators' concerns? How do they craft narratives that will speak to their readerships' sensibility, while reinventing the genres they find most familiar? Finally, literary critics have generally failed to recognize the contributions of most of these works to autobiographical studies and American Indian literature; hence, my dissertation brings these authors into discussions from which they have previously been excluded and highlights their literary achievements.

The Green Spiral: Policy-Industry Feedback and the Success of International Environmental Negotiation

Kelsey, Sarah Manina University of California, Berkeley 2014 해외박사(DDOD)

States cannot yet consistently solve international environmental problems requiring cooperation. Some international environmental negotiations result in clear successes. Others seem to fail or simply flatline, failing to progress beyond initial modest progress, even when they apply the "lessons learned" from prior rounds of negotiation. Existing scholarship fails to fully explain this variation. This lack is particularly troubling given that major environmental negotiations often address serious, even existential threats that appear to require international cooperation to effectively address. Existing theory that attempts to explain negotiation success and failure focuses on a variety of factors: (1) the advancement of knowledge and structures for the dissemination of knowledge; (2) institutional features such as treaty design, particularly features designed to solve problems of collective action; (3) structural features of the issue area, such as the scope and complexity of the problem or the existing configuration of relevant interests at the domestic level; and (4) a variety of miscellaneous factors such as leadership. But even taken collectively, these existing lines of explanation do not coherently explain the variation seen even within two key issue areas, ozone and climate change. Many success factors seen in ozone were present in climate change as well, but failed to lead to success there. On the other hand, one real differentiator between ozone and climate -- the greater difficulty of the climate problem -- appears to explain negotiation outcome but does not make sense given that unilateral action has been possible at the domestic level. If climate change is simply too daunting to address, why have some states still engaged in significant unilateral regulation?. A plausible answer lies in a process largely unutilized by previous scholarship on international negotiations: policy-industry feedback processes, which I refer to as the "green spiral." In such feedback processes, initial policy moves lead to adaptive industry responses, such as changes in capital investment. These adaptive responses actually change material industry interests, stimulating adaptation in existing "substitutable" industries that can adapt, growth in "winner" industries that benefit from regulation, and shrinkage in "loser" industries that bear high costs from regulation. In other words, these adaptive responses shrink coalitions against regulation, and grow coalitions for regulation. These changes in turn feed back into policymaking by increasing the political viability for international cooperation or regulation, allowing more regulation in the next round of negotiation or policymaking. More stringent regulation in the next round then triggers further industry reconfiguration; and so on, in a policy-industry feedback spiral. Green spiral processes do not always occur; and they may occur at the domestic level (as a feature of domestic policymaking) even when they do not occur at the international level. In this dissertation, I argue that their presence or absence at the international level explains the contrasting success and failure of the ozone and climate negotiations; and that the same dynamics explain variation at the national level seen within cases. In addition to characterizing these processes in ozone and climate, I explore the scope conditions for and policy implications of these processes in environmental negotiation and policymaking generally. Finally, I discuss the implications of this research project for existing and current scholarship.

Photography in the field: Timothy O'Sullivan and the Wheeler Survey, 1871--1874 (George Montague Wheeler)

Kelsey, Robin Earle Harvard University. 2000 해외박사

Brownfield Action: An education through an environmental science simulation experience for undergraduates

Kelsey, Ryan Daniel Columbia University Teachers College 2003 해외박사(DDOD)

Brownfield Action is a computer simulation experience used by undergraduates in an Introduction to Environmental Science course for non-science majors at Barnard College. Students play the role of environmental consultants given the semester-long task of investigating a potentially contaminated landsite in a simulated town. The simulation serves as the integration mechanism for the entire course. The project is a collaboration between Professor Bower and the Columbia University Center for New Media Teaching and Learning (CCNMTL). This study chronicles the discovery, design, development, implementation, and evaluation of this project over its four-year history from prototype to full-fledged semester-long integrated lecture and lab experience. The complete project history serves as a model for the development of best practices in contributing to the field of educational technology in higher education through the study of fully designed and implemented projects in real classrooms. Recommendations from the project focus on linking the laboratory and lecture portions of a course, the use of simulations (especially for novice students), instructor adaptation to the use of technology, general educational technology project development, and design research, among others. Findings from the study also emphasize the uniqueness of individual student's growth through the experience, and the depth of understanding that can be gained from embracing the complexity of studying sophisticated learning environments in real classrooms.

The role of home visitation in improving outcomes for teenage mothers and their children: Evidence from the Teenage Parent Home Visitor Services Demonstration

Kelsey, Meredith Claire University of Pennsylvania 2000 해외박사(DDOD)

Despite decades of policy interventions and research, adolescent childbearing continues to be one of the nation's greatest social problems. This dissertation presents findings from a federally funded demonstration project that was designed to fill some of the knowledge gap regarding the effectiveness of paraprofessional home visitation as a supplement to welfare support services. This large-scale, randomized field project operated in three U.S. cities over the three-year period 1995–1997. Serving representative samples of all first-time teenage mothers who entered the welfare system during this period, the demonstration programs aimed to reduce the incidence of repeat pregnancies among teenagers on welfare, enhance their parenting skills, and supplement the existing welfare-to-work program through the provision of weekly home visits made by paraprofessional home visitors. Results from this study indicate that paraprofessional home visitors were moderately successful in achieving some of the demonstration goals of improved self-sufficiency. However, the programs' effects were concentrated among specific program sites or sample subgroups. The demonstration programs did not lower the incidence of repeat pregnancy. However, they did promote greater use of condoms and of passive forms of contraception. The results are discussed in the context of the program implementation findings. This dissertation adds to the existing knowledge base regarding the efficacy of various strategies for improving outcomes for teenage mothers and their children. The results offer guidance to policy makers in making decisions as to whether or not states and/or local welfare offices should provide paraprofessional home visitor services as enhancements to existing welfare-to-work programs and, if they choose to provide paraprofessional home visitor services, how best to design, manage, and target the home visitor services.

A structural investigation of ambient and high pressure glasses and minerals using NMR spectroscopy

Kelsey, Kimberly Erin Stanford University 2008 해외공개박사

This work uses nuclear magnetic resonance spectroscopy (NMR) to study questions of cation ordering in ambient pressure aluminosilicate glasses and minerals as well as the pressure-induced structural changes within aluminosilicate glasses. We start by determining the 17O NMR parameters for the minerals jadeite, pyrope, grossular, and mullite for use as crystalline model compounds to aid interpretation of high pressure glass spectra. Next, along the pyrope-grossular join, 17O NMR shows that Ca and Mg distribute randomly over the different oxygen sites and there are two different intermediate or mixed (Ca+Mg) sites with different cation-oxygen bond lengths. Similarly, ambient pressure glasses along the same join were studied using 17O NMR and 27Al NMR. We are able to quantify the [5]Al and observe that the Ca is preferentially associated with the bridging oxygen (BO) and the Mg with the non-bridging oxygen (NBO), and this preference increases with increasing Al/Si. In the first high pressure study, we use both NMR and La-EXAFS to observe Li-, La-, Fe-, and Sc-containing aluminosilicate glasses. The Li-containing glasses have Al coordinations and densities that increase as predicted by cation field strength, however the La glasses have significantly lower Al coordinations, likely related to an increase in the La coordination. 17O NMR reveals that the Li-containing glasses are consistent with a mechanism that generates [5,6]Al at the expense of the NBO, while the La-containing glasses have virtually unchanging oxygen spectra with increasing pressure. The final high pressure study provides the first direct evidence for both highly coordinated Si and Al present in the same glass. We observe that both the average Si and Al coordination numbers decrease with increasing Al/Si, however the combined (Si+Al) coordination number increases.

Culture care values, beliefs, and practices of Mexican American migrant farm workers related to health promoting behaviors

Kelsey, Beth Marie Ball State University 2005 해외박사(DDOD)

The purpose of this study was to describe, explicate, and systematically analyze the culture care values, beliefs, and practices of migrant farm workers related to health promoting behaviors in context of their temporary living accommodations and work setting in two small towns in east central Indiana. The goal of this study was to generate knowledge regarding culture care values, beliefs, and practices of migrant farm workers related to health promoting behaviors. Such knowledge can be used by nurses to provide culturally congruent care which can influence migrant farm workers' health and well-being. The theoretical framework for the study was Leininger's Theory of Culture Care Diversity and Universality. The qualitative ethnonursing research method was used. Semi-structured interviews were conducted using both an ethnonursing inquiry guide and an ethno-demographic information guide developed by the researcher. Sixteen key informants and three general informants participated in the study. Informants were purposefully selected for knowledge of migrant farm life and willingness to share this knowledge with the researcher. Key informants were Mexican American migrant farm workers in east central Indiana for farm and tomato factory work from July through October, 2004. General informants were health and social service workers who provided care for the migrant farm workers. Three key informants were interviewed twice each. All other informants were interviewed once. Interviews took place in the informants' homes and at a local food pantry. Interviews were audio taped and transcribed verbatim. Four major themes were synthesized from the research data: (a) health promoting behaviors are recognized and valued by migrant farm workers but are influenced by economic and political/legal factors in the social structure; (b) traditional gender roles of migrant farm worker men and women influence health promoting behaviors; (c) professional caring is viewed by migrant farm workers as respect through the use of the Spanish language and acceptance of culture care values, beliefs, and practices; and (d) health promoting behavior of migrant farm workers is influenced both by traditional culture care values and beliefs and by knowledge acquired through diverse formal and informal education. Findings were discussed in relation to Leininger's three modes of culture care action for nurses: culture care preservation/maintenance, accommodation/negotiation, and repatterning/restructuring.

The vulnerability of self-report measures of psychopathy to positive impression management: A simulation study with inmates

Kelsey, Katherine R University of North Texas 2014 해외박사(DDOD)

Psychopaths have long been characterized as having a remarkable disregard for the truth, to the extent that deceit is often regarded as a defining characteristic of the syndrome. Scholars described heightened concerns about how psychopaths' deceitful and manipulative nature could significantly obstruct evaluations of psychopathy. The accurate evaluation of psychopathy is very important in forensic and correctional settings, and in such issues as risk assessment or dangerousness. Although the PCL-R is considered the quasi-gold standard when it comes to evaluating psychopathy, self-report measures have become more widely available and researched. Very few studies specifically evaluated response styles and self-report psychopathy measures despite the significant concerns regarding psychopathy and deception. The current study evaluated the ability of inmates with different levels of psychopathy to successfully engage in positive impression management on the SRP-4, LSRP, and PPI-R. Utilizing a repeatedmeasures, within-subjects design, 78 male inmates completed the study under genuine and simulation conditions. Overall, inmates were able to significantly lower their scores on all three self-report measures and achieved scores equivalent to and even lower than college and community samples. Inmates with higher levels of psychopathy were able to achieve larger decreases in scores on the PPI-R and on several scales for each measure. Another key finding was the identification of promising PPI-R Virtuous Responding Scale cut scores that can be utilized within forensic populations. Results indicate self-report measures should not be used to replace the PCL-R or comprehensive assessment of psychopathy in forensic evaluations; however, they do provide additional useful information and may be beneficial in other clinical settings.

The influence of African-American faculty members on African-American student retention and graduation at a predominantly White institution

Kelsey-Brown, Monica Denise The University of Wisconsin - Madison 2001 해외박사(DDOD)

This study explored the influence of African-American faculty members on the retention and graduation rate of African-American students at a predominantly White institution. Influence is defined as follows: (1) Viewing the person as a role model, i.e., knowing that the professor exists and is present on campus; (2) Brief coordinated interaction with the professor, i.e., being introduced to the individual at a function and having some kind of dialogue, either significant or non-significant to the student; (3) Establishing an ongoing mentoring relationship with the professor; (4) Having the individual as a professor in one of their courses. The four components of Collins' (1992) theoretical framework, African Feminist Epistemology were used as an analytical framework. Those components are dialogue, caring, experience and accountability. This is a qualitative study using phenomenological interviews, coding and survey data. Included is a description of the university setting and an academic profile of the students who were selected to serve as interview respondents. Major findings of the study are: (1) African-American faculty were influential in the retention and graduation of African-American students at “RU.” Although they weren't the primary focus of this study, African-American staff were also mentioned in a few cases as being influential; (2) African-American graduates felt the need for predominantly White institutions to hire more African-American faculty to assist in the retention and graduation of African-American students; (3) African-American faculty can assist African-American students in negotiating predominantly white institutions through their peer relationships with White faculty. Implications for future research include: the influence of African-American faculty on White students at predominantly White institutions; studying the topic from the perspective of African-American faculty and/or staff members; researching innovative strategies to recruit and retain African-American faculty.