4 resultados para Carol Griffith

em Duke University


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Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.

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*Designated as an exemplary master's project for 2015-16*

This paper examines how contemporary literature contributes to the discussion of punitory justice. It uses close analysis of three contemporary novels, Margaret Atwood’s The Heart Goes Last, Hillary Jordan’s When She Woke, and Joyce Carol Oates’s Carthage, to deconstruct different conceptions of punitory justice. This analysis is framed and supported by relevant social science research on the concept of punitivity within criminal justice. Each section examines punitory justice at three levels: macro, where media messages and the predominant social conversation reside; meso, which involves penal policy and judicial process; and micro, which encompasses personal attitudes towards criminal justice. The first two chapters evaluate works by Atwood and Jordan, examining how their dystopian schemas of justice shed light on top-down and bottom-up processes of punitory justice in the real world. The third chapter uses a more realistic novel, Oates’s Carthage, to examine the ontological nature of punitory justice. It explores a variety of factors that give rise to and legitimize punitory justice, both at the personal level and within a broader cultural consensus. This chapter also discusses how both victim and perpetrator can come to stand in as metaphors to both represent and distract from broader social issues. As a whole, analysis of these three novels illuminate how current and common conceptualizations of justice have little to do with the actual act of transgression itself. Instead, justice emerges as a set of specific, conditioned responses to perceived threats, mediated by complex social, cultural, and emotive forces.