Trim24 in Normal & Malignant Hematopoiesis

Treatment for acute myeloid leukemia (AML) has changed little in the past four decades. For the majority of AML patients, current treatment options include chemotherapy and allogeneic stem cell transplants, which also involves high-dose chemotherapy or radiation treatment. These options have little success in the long-run, as only an estimated 26% of patients survive five years post-diagnosis. In efforts to address this low survival rate, interest has increased for targeting epigenetic pathways in AML. This focus stems from the discovery that AML is frequently driven by blockades on hematopoietic stem cell differentiation, which involves a series of coordinated epigenetic changes. Given its reported roles as an epigenetic reader, stem cell regulator, and known oncogene, we investigated TRIM24 for putative relevance in AML. Expression data from previous studies have also suggested roles for TRIM24 in chronic myeloid leukemia and acute lymphocytic leukemia; however, no studies to date have reported measurements of TRIM24 in AML from an in vivo system. Here, we report that low TRIM24 mRNA expression in human AML patients (in TCGA) correlates with poor survival. Additionally, this association was found to be independent of gene expression signatures of prognostic significance, such as Gentles leukemic stem cell signature. Furthermore, loss of Trim24 in murine, MLL-AF9-driven AML worsened survival and increased leukemic stem cell numbers, while having no observed effects on normal hematopoiesis. These results lay the groundwork for future investigations of the role of TRIM24 in AML, which has the potential to aid development of novel therapeutic strategies

FALLING MEN IN 9/11 AMERICAN FICTION

“Falling Men in 9/11 American Fiction Gender critics such as Judith Butler and Michael Kimmel argue that post-9/11 American culture has embraced a traditional gender binary that positions men as the dominant protectors of women, children, and the nation as a whole, exemplified by the widespread veneration of heroic firefighters, soldiers, and the civilians of flight 93 in the media (Kimmel 249). This regression reinforces hegemonic masculinity in American culture, which R.W. Connell defines as “the pattern of practice (i.e., things done, not just a set of role expectations or an identity) that allow[s] men’s dominance over women to continue” (Connell and Messerschmidt 832). Christine Beasley has “demassified” hegemonic masculinity by dividing it into two categories: sub-hegemonic masculinity, which refers to traditional modes of dominant masculinity that emphasize brawn and physical aggression, and supra-hegemonic masculinity, which designates the increasingly sublimated practices of dominance undertaken by business professionals. Rather than focusing on the sub-hegemonic ideals venerated after 9/11, my study will focus on a figure of supra-hegemonic masculinity that was suppressed in the United States after 9/11: the American businessman, who embodied the neoliberal values against which 9/11 was staged as a symbolic critique. I argue that this figure is focalized in several important works of 9/11 fiction, which attempt to reintroduce the centrality of this figure in the historical and geopolitical context of American capitalism in transnational markets. Falling Men in 9/11 American Fiction” explores how novelists such as Don DeLillo, Laila Halaby, Amy Waldman, and Teju Cole identify the absent cause of 9/11 to be aggressive masculine dominance as sublimated through American capitalism. This dominance is depicted in the figuration of domestic gender relations in a way that mirrors and critiques American geopolitical relations abroad. Thus, when Richard Gray claims that post-9/11 American novelists “vacillate […] between large rhetorical gestures acknowledging trauma and retreat into domestic detail,” and further argues that “the link between the two is tenuous, reducing a turning point in national and international history to little more than a stage in a sentimental education,” he is in fact getting it backwards: rather than reducing 9/11 entirely to domestic trauma, this fiction situates itself within the domestic space from where it can dramatize the outward influence that interpersonal gender relations have on oppressive American foreign policies abroad, and vice versa (134). Therefore, in a synthesis of a key debate framed by Richard Gray and Michael Rothberg, I argue that this fiction is inherently dialectical: its “centripetal” orientation, rather than being simply reductive and “sentimental,” establishes the domestic analogue for a greater “centrifugal” critique of hegemonic American ideology as it manifests itself abroad – underscoring that an understanding of domestic gender relations is essential to any analysis of American culture and fiction after 9/11

Fatigue and Crack-Growth in 7050-T7451 Aluminum Alloy under Constant- and Variable-Amplitude Loading

Fatigue and crack-growth tests were conducted on 7050-T7451 aluminum alloy under a wide range of loading conditions. Crack-growth tests were conducted on compact, C(T), specimens under constant-amplitude loading, single-spike overloads, and a simulated aircraft spectrum loading. Fatigue tests were also conducted on single-edge-notch bend, SEN(B), specimens under constant-amplitude loading and three aircraft load spectra. The FASTRAN, life-prediction code, was used to make crack-growth predictions on the C(T) specimens; and to make fatigue-life calculations using a 12-micrometer initial flaw size at the center of the edge-notch on the SEN(B) specimens. The predictions agreed fairly well with most of the tests, except the model was unconservative on the single-spike overload tests and the severe spectrum Mini-TWIST+ Level 1 tests. The discrepancy was suspected to be caused by a low constraint factor and/or crack paths meandering around overload plastic zones. A roughness- and plasticity-induced crack-closure model would be needed to improve the model