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The targeted inactivation of oncogenes offers a rational therapeutic approach for the treatment of cancer. However, the therapeutic inactivation of a single oncogene has been associated with tumor recurrence. Therefore, it is necessary to develop strategies to override mechanisms of tumor escape from oncogene dependence. We report here that the targeted inactivation of MYC is sufficient to induce sustained regression of hematopoietic tumors in transgenic mice, except in tumors that had lost p53 function. p53 negative tumors were unable to be completely eliminated, as demonstrated by the kinetics of tumor cell elimination revealed by bioluminescence imaging. Histological examination revealed that upon MYC inactivation, the loss of p53 led to a deficiency in thrombospondin-1 (TSP-1) expression, a potent antiangiogenic protein, and the subsequent inability to shut off angiogenesis. Restoration of p53 expression in these tumors re-established TSP-1 expression. This permitted the suppression of angiogenesis and subsequent sustained tumor regression upon MYC inactivation. Similarly, the restoration of TSP-1 alone in p53 negative tumors resulted in the shut down of angiogenesis and led to sustained tumor regression upon MYC inactivation. Hence, the complete regression of tumor mass driven by inactivation of the MYC oncogene requires the p53-dependent induction of TSP-1 and the shut down of angiogenesis. Notably, overexpression of TSP-1 alone did not influence tumor growth. Therefore, the combined inactivation of oncogenes and angiogenesis may be a more clinically effective treatment of cancer. We conclude that angiogenesis is an essential component of oncogene addiction.

The ocean makes up over 97% of the Earth’s biosphere and much of it is located within deep-sea habitats. Life at these depths must possess adaptations for growth at high hydrostatic pressures. Microorganism that grow preferentially at elevated pressures are termed “piezophiles.” Although prior studies have examined the piezophilic adaptations of Gram-negative microbes, little attention has been given to Gram-positive bacteria. In this project, I examined one of the few Gram-positive piezophiles, Carnobacterium sp. AT7. Two lineages of AT7 were subjected to progressively increasing hydrostatic pressures over the course of 130 generations. From these adaptive laboratory evolution (ALE) lineages, I obtained mutant strains which possessed improved rates of growth at high pressure and increased upper pressure limits. During these experiments, it was discovered that incubation of AT7 under stressful, high hydrostatic pressure for approximately 200 hours resulted in the acquisition of greatly improved high pressure growth in a single incubation cycle. Interestingly, cells derived from these incubations did not display stable high pressure growth and are presumed to have gained this ability through a physiological rather than genetic mechanism. Because it is well known that high pressure growth requires the production of sufficient proportions of membrane unsaturated fatty acids, it was investigated whether the long-term incubation cultures display increased unsaturated fatty acid fractions. Surprisingly, the Carnobacterium high pressure growth mutants do not produce increased proportions of unsaturated fatty acids. It was likewise discovered that these ALE-derived mutants do not possess alterations in cell size or shape. This thesis provides data and strains with which to begin to shed light on the processes employed by Gram-positive bacteria to adapt to elevated high pressure conditions.

With the rapid growth of technology, the use of computer-based test interpretation (CBTIs) has seen immense growth in assisting objective personality testing and case conceptualization in recent years. While previous studies have examined the validity and clinical utility of CBTIs for the MMPI-2 generally, the present study examined the effect of a specific diagnosis of psychosis on the utility of four commercially available CBTIs: the Pearson report, the Pearson MMPI-2 Rf report, the Psychological Assessment Resource Corporation report, and the Behaviordata report along 12 dimensions. This study employed a consumer satisfaction design with participants being clinicians. Results found variability among the CBTIs along the 12 dimensions. Results showed the Pearson and Psychological Assessment Resource Corporation reports were viewed more favorably when used with a profile of a diagnosis of a psychotic disorder, while Behaviordata was on the lower end of scores.

[...]I used to associate video games with hyperfo-cused, headset-wearing young men who mutter angrily at a TV screen while playing \"Call of Duty\" or similar shooter games. Sam, a half-Korean boy who lives with his pizzeria-owning grandparents in K-Town, recently lost his mother and badly injured his left foot in a traumatic car accident; Sadie, a wealthy Jewish girl from Beverly Hills, spends days and nights at the hospital with her sister in the pediatric oncology wing. Following the brief legalization of gay marriage in San Francisco in 2004, which lasted several months before all 4,000 newly issued marriage licenses (including one of the book's supporting character's) were retracted, the video game world became a space where in-game marriage ceremonies could be performed between all people, no matter their gender.

The timer on my phone and on my stove go off at once, and I rush to add cabbage to the stew and then put on oven mitts to remove the steaming sea bass before it overcooks. The main character, Evelyn (Michelle Yeoh), is a graying Chinese American woman who runs a failing laundromat, while living in the apartment above it with her husband Waymond (Ke Huy Quan) and her elderly father (James Hong). The storyline goes back and forth from mundane to absurd, revealing some universes where Evelyn had chosen to stay home rather than move to the United States with her now husband, and other universes where a raccoon lives in the chef hat of her chef colleague, teaching him how to cook in \"Rata-touille\" fashion.

Sergius and Bacchus, Roman soldiers and Christian martyrs in the late third century, venerated by queer Catholics as models of same- sex love in early Chris -tianity. In their eyes, queer Catholics are just \"making things up,\" or worse, merely creating scandal by suggesting the queemess of the saints. For queer and marginalized Catholics, recovering traces of our presence from a predetermined archive is not enough.

Whether I and many other non-Americans who live in the U.S. would be able to start a family and what rights our children might have in this country, depend on whether such policies continue. Because of these and other complex circumstances in my own life, family - as well as fulfilling my maternal instincts of loving small animals - will always look different for me. The church's view of childbirth, or intention to conceive children, as a central and crucial part of marriage continues to contribute to its theological justifications against lesbian and gay relationships, its prohibition on artificial contraception and its views on gender complementarity While the church acknowledges the life-giving vocations of celibate religious men and women who dedicate their lives in service of others, it does not honor that option for married couples who choose to dedicate their lives to service in ways other than childbirth or adoption. [...]the story of St. Joseph, who himself also never had biological children, represents just one example of the complexity and diversity of families present within and beyond the church.