Event-by-Event Jet Quenching

High momentum jets and hadrons can be used as probes for the quark gluon plasma (QGP) formed in nuclear collisions at high energies. We investigate the influence of fluctuations in the fireball on jet quenching observables by comparing propagation of light quarks and gluons through averaged, smooth QGP fireballs with event-by-event jet quenching using realistic inhomogeneous fireballs. We find that the transverse momentum and impact parameter dependence of the nuclear modification factor R_AA can be fit well in an event-by-event quenching scenario within experimental errors. However the transport coefficient qhat extracted from fits to the measured nuclear modification factor R_AA in averaged fireballs underestimates the value from event-by-event calculations by up to 50%. On the other hand, after adjusting qhat to fit R_AA in the event-by-event analysis we find residual deviations in the azimuthal asymmetry v_2 and in two-particle correlations, that provide a possible faint signature for a spatial tomography of the fireball.Comment: 8 pages, 5 figures; v2: new figure added, small changes and fixes, this version published in Phys. Lett.

p53 Regulates Stemness in Mucoepidermoid Carcinoma

Salivary gland carcinomas are rare and heterogenous malignancies that present diagnostic and treatment challenges for clinicians. Amongst them, mucoepidermoid carcinoma (MEC) is the most common salivary gland cancer. Little is known about the pathobiology of MEC, partly due to limited preclinical research models. Our group and others have shown that cancer stem cells (CSC), ALDHhighCD44high cells, drive MEC tumorigenesis. We have found that treatment of human MEC cell lines (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) with sub-lethal doses of MI-773, an MDM2 inhibitor that results in accumulation of p53 and activation of downstream signaling, significantly decreases the CSC fraction both in vitro and in xenograft tumors. Furthermore, upon p53 activation there is a decrease in Bmi-1 protein levels. Bmi-1 has been widely studied as a marker of stem cell and CSC self-renewal. We hypothesized that the p53 pathway regulates MEC CSC maintenance. In this thesis we aim to: 1) determine the role of p53 in MEC CSC fate and 2) investigate the therapeutic potential of MDM2 inhibitors in murine models of MEC. We found that while activation of p53 signaling does not cause apoptosis of MEC CSCs, it changes their cell cycle profile through p21. Furthermore, p53 activation causes a decrease in the sphere forming ability and self-renewal of MEC CSCs and in their Bmi-1 protein levels, independent of p21 signaling. Additionally, we found an induction of pan-cytokeratin expression, indicating differentiation of the CSCs. In contrast, shRNA downregulation of p53 resulted in increased Bmi-1 protein levels, enhanced CSC self-renewal, and an expansion of the stem cell pool in vivo. While no changes in Bmi-1 mRNA levels were detected after treatment with MDM2 inhibitors, we found a decrease in Bmi-1 protein stability. Importantly, we found that therapeutic activation of p53 using MI-773 prevented tumor recurrence in mice. Further characterization of the regulation of Bmi-1 by p53 still needs to be evaluated. These results indicate p53 signaling regulates the cell cycle and self-renewal of MEC CSC through p21 and Bmi-1 signaling axes. This body of work enhances our understanding of the role of p53 in MEC CSC biology and gives insight into the potential therapeutic benefits of MDM2 inhibitors or other p53-activating therapies for MEC.PHDCancer BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/162925/1/chrisrr_1.pd

From Panic to Pity: Circuits and Circulations of the Contemporary Anti-Trafficking Crusade

The creation, implementation, and ratification of the Trafficking Victims Protection Act (TVPA), as well as the growth of parallel private initiatives against human trafficking, have emerged from a neoliberal political agenda that focuses on redefinitions of labor, sexuality, securitization of humanitarian campaigns, and immigration policies. In this thesis, I explore some of the meanings and effects of those redefinitions by focusing on the affective registers of pity and panic in their ability to mobilize publics toward restrictive forms of assistance to real and imaginary victims of the so-called phenomenon of “modern-day slavery.

EL CONTEXTO SOCIAL Y EL CAMBIO TIPOLÓGICO Y TECNOLÓGICO EN EL DISEÑO DE LAS VIVIENDAS IRREGULARES EN EL ÁREA NATURAL PROTEGIDA DEL PARQUE NACIONAL DEL NEVADO DE TOLUCA: CASO DE ESTUDIO, RAÍCES Y LOMA ALTA

Como una alternativa al análisis del deterioro del ambiente y la reducción de los recursos naturales, este artículo presenta un criterio metodológico para explicar, cómo el cambio tipológico y tecnológico de las viviendas irregulares, han establecido el detrimento del medio ambiente, así mismo, se muestra cómo se ha generado la pérdida del bosque