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Antibodies and humoral memory are key components of the adaptive immune system. We consider and computationally model mechanisms by which humoral memory present at baseline might instead increase infection load; we refer to this effect as EI-HM (enhancement of infection by humoral memory). We first consider antibody dependent enhancement (ADE) in which antibody enhances the growth of the pathogen, typically a virus, and typically at intermediate "Goldilocks" levels of antibody. Our ADE model reproduces ADE in vitro and enhancement of infection in vivo from passive antibody transfer. But notably the simplest implementation of our ADE model never results in EI-HM. Adding complexity, by making the cross-reactive antibody much less neutralizing than the de novo generated antibody or by including a sufficiently strong non-antibody immune response, allows for ADE-mediated EI-HM. We next consider the possibility that cross-reactive memory causes EI-HM by crowding out a possibly superior de novo immune response. We show that, even without ADE, EI-HM can occur when the cross-reactive response is both less potent and "directly" (i.e. independently of infection load) suppressive with regard to the de novo response. In this case adding a non-antibody immune response to our computational model greatly reduces or completely eliminates EI-HM, which suggests that "crowding out" is unlikely to cause substantial EI-HM. Hence, our results provide examples in which simple models give qualitatively opposite results compared to models with plausible complexity. Our results may be helpful in interpreting and reconciling disparate experimental findings, especially from dengue, and for vaccination.

The Maritime Area Denial Mine with Autonomous Navigation (MADMAN) project provides a means for asserting maritime dominance through integration of intelligence into mines. This project identifies a path toward reinvigorating mine warfare innovation to develop the mine of the future, MADMAN. Modeling and simulation tools reveal that the highest mission success probabilities support an unmanned underwater vehicle (UUV) option. By integrating current, available systems, a resulting system of systems provides a cost-effective means to develop a mine that is capable of autonomously transiting to a location, arming itself, performing missions, and increasing personnel safety. Using a capability engineering approach, this study identifies an overall target probability of success for the system of systems. This overall success probability decomposes the individual systems and highlights their level of impact on overall success. Analyzing these impacts allows tailoring of each system to provide improved mining and cost savings while meeting project requirements. Resulting collaboration between UUV designers and military engineers ensures a modern arsenal for a modern world. http://archive.org/details/developingthemin1094559582 Civilian, Department of the Navy Civilian, National Aeronautics and Space Administration Civilian, Department of the Navy Civilian, Department of the Navy Lieutenant Commander, United States Navy Approved for public release; distribution is unlimited.