3 resultados para Buddha (The concept)
em Duke University
Resumo:
BACKGROUND: A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective. METHODS AND RESULTS: Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide) chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06). Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8%) of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), representing a viable alternative therapy. CONCLUSIONS: Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding microRNA and mRNA expression profiles. Importantly, we also present evidence to support the concept that analysis of molecular variables can present a rational strategy to identifying alternative therapeutic opportunities.
Resumo:
© 2016 The Author(s).Mid-ocean ridges display tectonic segmentation defined by discontinuities of the axial zone, and geophysical and geochemical observations suggest segmentation of the underlying magmatic plumbing system. Here, observations of tectonic and magmatic segmentation at ridges spreading from fast to ultraslow rates are reviewed in light of influential concepts of ridge segmentation, including the notion of hierarchical segmentation, spreading cells and centralized v. multiple supply of mantle melts. The observations support the concept of quasi-regularly spaced principal magmatic segments, which are 30-50 km long on average at fast- to slow-spreading ridges and fed by melt accumulations in the shallow asthenosphere. Changes in ridge properties approaching or crossing transform faults are often comparable with those observed at smaller offsets, and even very small discontinuities can be major boundaries in ridge properties. Thus, hierarchical segmentation models that suggest large-scale transform fault-bounded segmentation arises from deeper level processes in the asthenosphere than the finer-scale segmentation are not generally supported. The boundaries between some but not all principal magmatic segments defined by ridge axis geophysical properties coincide with geochemical boundaries reflecting changes in source composition or melting processes. Where geochemical boundaries occur, they can coincide with discontinuities of a wide range of scales.
Resumo:
*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.
