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Although American women have had a long, distinguished history working for the armed forces of the United States, the American military has been struggling with the integration of women into official combat positions from the colonial era until present day. Gender stereotypes regarding women’s ability to perform combat duty permeate the debate surrounding their inclusion into combat roles. Opponents of women in combat roles point to women’s overall physical fitness, female strength, pregnancy, motherhood, sexual activity and psychological stress as reasons to bar women from combat duty. They also question women’s ability to cope with the military’s existing male-dominated martial culture where sexual harassment continues to be a problem. Opponents of women in combat have questioned the effect that female integration will have on unit cohesion. Furthermore, they have argued, without evidence, that women cannot or should not kill, that the presence of women in combat will make the entire unit appear weak to the enemy and that servicemen will simply never get used to the idea of fighting alongside females since many of them were raised to believe they are the protectors of women. Research shows that not only are these assumptions about women and their integration into combat roles wrong but they are also damaging women’s careers inside the military and hindering progress towards equal citizenship for women in the broader society. By vigorously challenging these gender stereotypes and examining the successes of women’s integration into combat positions in other countries, the American military can find ways to improve the inclusion of servicewomen into combat roles. Evidence suggests that such a change would mark advancement toward equal citizenship rights and responsibilities for women both inside and outside the military as well as progress toward gender justice. This study utilizes a combination of qualitative and quantitative data gathered from books, articles, websites, research centers, congressional reports, research institute reports and scholarly journals to show how the American military’s combat exclusion guidelines for women began, challenge the gender stereotypes employed to justify it, explore the fairness of the policy toward women both inside and outside the armed forces, study the efficacy of the policy within the military as an institution and explore ways the American military can improve the integration of women into combat roles by adopting some of the successful strategies of combat inclusive countries such as Israel and Norway.

Ellipticine, an anticancer agent, has had limited clinical success due to low solubility and toxic side effects. To overcome these limitations, a panel of novel ellipticine isomers were designed and synthesised with the aim of evaluating their anti-cancer effects on selected cancer cell lines. A preliminary NCI 60-cell screen demonstrated that these isoellipticines displayed promising anti-tumour activity across a number of different cell types, particularly leukaemia cell lines. We consequently examined the effect of these derivatives in detail on the Acute Myeloid Leukaemia (AML) cell line, MV4-11. Cell cycle analyses revealed that the compounds had a range of distinctive cell cycle effects on MV4-11 cells. 7-Hydroxyisoellipticine showed the most promise with respect to cytostatic activity. We demonstrated that this compound inhibited proliferation of leukaemia cells by preventing cells from progressing from G2 phase. Our research suggests that this is mediated by an induction of reactive oxygen species (ROS), which in turn activates the DNA damage response pathway. More extensive research on the source of ROS generated by the most potent derivative, 7-formyl-10-methylisoellipticine showed that this compounds cytotoxicity is partially mediated by an induction of mitochondrial derived reactive oxygen species (ROS). We showed that 7-formyl-10-methylisoellipticine has synergistic effects when used in combination with the clinically used AML drug, daunorubicin, as well as DPI, a Nox inhibitor. Additionally, combination experiments with other drugs served to give us a deeper insight into 7- formyl-10-methylisoellipticine mechanism of action. 7-Formyl-10-methylisoellipticine also displayed promising in vivo results. Treatment resulted in a lack of toxicity, as measured by body weight changes and liver enzyme analyses. Most importantly, 7-formyl-10-methylisoellipticine demonstrated potent anti-tumour activity in the in vivo xenograft mouse model, implying the potential of isoellipticines as novel chemotherapeutic agents in the treatment of leukaemia. In summary, this study provides for the first time detailed cellular information on the potential use of isoellipticines as chemotherapeutic agents. Our study documents for the first time, the therapeutic potential of an isoellipticine compound in a subcutaneous AML cell-derived xenograft (CDX) model. By probing the mechanism of action of this novel compound class we have uncovered a potential clinical application in the field of adjuvant therapy. We anticipate that the recent research on ellipticine derivatives, such as this study, will lead the development of an ellipticine analogue that may be employed clinically.