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RISS 인기검색어
- 검색키워드
- 저자 : Sievers, Wolfgang (검색결과 7 건)
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Bad Timing: Early Molecular Events Impact Tumor Fate
Sievers, Chelsie Kohns ProQuest Dissertations & Theses The University of 2017 해외박사(DDOD)
Colorectal cancer encompasses multiple subtypes of tumors that are defined by their molecular and histological features. Historically, these features were thought to be attained by the sequential acquisition of driver mutations over time. However, this model of tumor evolution fails to account for the variability in polyp growth behavior and the ubiquitous presence of intratumoral heterogeneity. These observations have led to new models of tumor evolution in which numerous molecular changes occur simultaneously during punctuation events. We sought to test this new conceptual framework by characterizing how and when crucial molecular characteristics are acquired and their impact on tumor evolution. Microsatellite instability (MSI) is common in many familial and sporadic colorectal cancers. We developed a more sensitive method for detecting MSI in tumors to determine when it is acquired. MSI can occur early in the development of adenomas from Lynch patients or it can occur late in the development of tumors with a serrated morphology. The early diagnosis of Lynch Syndrome could be of immense clinical benefit as each patient has, on average, three afflicted relatives, many of whom go undiagnosed until they present with a cancer. Our analysis of intestinal tumors also revealed that other molecular events occur earlier than predicted. Colorectal tumors can have different fates: growth, stasis, or regression. The comparison of gene expression in growing tumors versus static tumors from mice revealed a gene signature that could distinguish between these types. The transcriptional changes were evident as soon as tumors were detectable. Similarly, in human colorectal tumors we found that subclones carrying pathogenic mutations arose when the tumors were quite small. Furthermore, we demonstrate that many of these subclonal mutations result from a very early punctuation event. Thus, our findings support the notion that early punctuation events can affect tumor fate. The finding of critical molecular events occurring very early on during tumorigenesis support the notion that some tumors might be "born to be bad." These novel insights may lead to more efficient screening recommendations, novel screening modalities, and improved treatment options for patients.
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Evidence of wonders: Writing American identity in the early modern transatlantic world
Sievers, Julie Ann The University of Texas at Austin 2004 해외박사(DDOD)
Narratives about "wonders" pervaded early modern European cultures. Reports of unusual phenomena such as "monster" babies, sea storms wrecking a ship, and the acts of demons permeated both popular and elite writings, from news reports to scientific journals. To date, research on these texts has concentrated on English or continental writers, not American colonials. Yet wonders played a potent role at the colonial margins of the expanding empires. Reclaiming these influential but forgotten texts, this dissertation investigates seventeenth-century New England wonder writings and their role in the political relationship between England and its American colonies. Ultimately, it shows how New England Congregationalists used transnational Protestant and scientific rhetorics to develop a discourse of political legitimacy and American exceptionalism, and in the process, created new forms of writing and speaking. The study begins by discussing the most publicized event of seventeenth-century New England, King Philip's War (1675--76), and the sensational reports about it written by individuals such as William Hubbard, Nathaniel Saltonstall, John Easton, and Increase Mather. These publications exemplify the identity politics at stake in texts about the colonies, especially in the narrative and reportage genres that would later carry wonder accounts. A second chapter re-examines this historical context from a broader angle, situating New England wonder writings within the period's transnational legal and philosophical discourse about empire, including John Cotton's influential rationale for banishing Roger Williams. The project then examines three case studies: (a) sea providence narratives (featuring Edward Gibbons' and Anthony Thacher's stories as recorded by John Winthrop, James Janeway, and Increase Mather); (b) natural history writings about "curious" objects, lightning storms, or apparitions (by John Winthrop, John Winthrop, Jr., Increase Mather, and Cotton Mather); and (c) published arguments about Salem witchcraft (by Cotton Mather, Deodat Lawson, and Increase Mather). By recovering the political and social fields that these texts were intended to negotiate, the project shows how New Englanders used the shocking and vivid subject matter of traditional narratives to transact a shift in group identity, emphasizing the Americanness of their experiences to assert their political and spiritual distinction.
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Sievers, Brittany Southern Illinois University at Carbondale ProQues 2020 해외박사(DDOD)
The purpose of both Study 1 and Study 2 was to experimentally examine the ways in which non-Latinx, White, European American individuals just world beliefs and color-blind racism may predict scapegoating behaviors directed at Black, African American and Brown, Latino men in the workplace. Participants were recruited via Amazon Mechanical Turk Prime. The main hypothesis for Study 1 was that just world beliefs would positively predict shame and guilt, shame and guilt would positively predict discipline, and that color-blind racism would mediate the relationship between shame and guilt and discipline. The overall scapegoating model was not supported, but individual pathways were significant. The main hypothesis for Study 2 was that just world-beliefs would positively predict threat of loss, threat of loss would positively predict discipline, and that color-blind racial ideology would mediate the positive relationship between threat of loss and discipline. The overall scapegoating model was not supported but the significance of individual pathways is discussed below. For Study 1 I found partial support for racial differences in discipline, but this was not found in Study 2. However, I did find that participants who were threatened with job loss in Study 2 assigned harsher discipline. In both Study 1 and Study two it was found that color-blind racism predicts harsher discipline. Future research and implications are discussed.
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