A Conflict Model for Strategists and Managers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67210/2/10.1177_000276427201500604.pd

The Political Economy of US Military Spending

The causes of the dramatic rise in military spending in the post-war era have been the subject of much political and academic controversy. No extant formulation seems to provide a compelling explanation of the dynamics involved in the levels of, and rates of change in, such spending. In light of this, the authors develop a new model, based mainly on a political-business cycle argument, to account for these dynamics. The basic proposition in this model is that variations in national defense spending arise from political considerations which are related to real and desired conditions within the national economy. Applying this model to the experience of the United States 1948-1976, the authors show that it has a large measure of empirical validity. If one removes the effects of war-time mobilization, it is clear that for the United States the principal driving forces in military spending dynamics were (1) the perceived utility of such spending in stabilizing aggregate demand, (2) the political or electoral value of the perceived economic effects arising out of such spending, and (3) the pressures of institutional-constituency demands.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68958/2/10.1177_002234337901600202.pd

TGF-β and CIS inhibition overcomes NK cell suppression to restore anti-tumor immunity

Antibodies targeting “immune checkpoints” have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8þ T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation. NK-cell antitumor function is dependent on the cytokine IL15. Ablation of the IL15 signaling inhibitor CIS (Cish) enhances NK-cell antitumor immunity by increasing NK-cell metabolism and persistence within the tumor microenvironment (TME). The TME has also been shown to impair NK-cell fitness via the production of immuno-suppressive transforming growth factor b (TGFb), a suppression which occurs even in the presence of high IL15 signaling. Here, we identified an unexpected interaction between CIS and the TGFb signaling pathway in NK cells. Independently, Cish- and Tgfbr2- deficient NK cells are both hyperresponsive to IL15 and hyporesponsive to TGFb, with dramatically enhanced antitumor immunity. Remarkably, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development, suggesting that combining suppression of these two pathways might represent a novel therapeutic strategy to enhance innate anticancer immunity.Fernando Souza-Fonseca-Guimaraes, Gustavo R. Rossi, Laura F. Dagley, Momeneh Foroutan, Timothy R. McCulloch, Jumana Yousef, Hae-Young Park, Jennifer H. Gunter, Paul A. Beavis, Cheng-Yu Lin, Soroor Hediyeh-Zadeh, Tania Camilleri, Melissa J. Davis, and Nicholas D. Huntingto