There exists a large collection of mathematical models to describe the immune system [116] . Here, we have proposed Boolean immunomic regulatory networks as a new mathematical model for immune system regulation. This is a dynamical system model, with parameters that can be estimated from immunomic microarray data. A somewhat similar concept was suggested in [102, 117] , where a network model for cytokine action was proposed, albeit without explicit reference to large-scale immunomic technology or regulatory T cell response. In addition, immune system regulatory networks have been previously discussed in the context of genomics [118] . The immunomic regulatory network model may be useful for computational knowledge discovery and simulation of regulatory mechanisms of the immune system in health and disease, which may lead to advances in practical applications (e.g., vaccine design) as well as in the basic scientific understanding of the immune system. " Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. RESULTS: 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0–38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early. The anthrax attacks that followed the events of September 11th, 2001 focused attention on the threat of terrorism with biological agents including variola major, the causative agent of smallpox [1] . There is concern that an attack with smallpox could result in many deaths because of the susceptibility of the U.S. population [2] [3] [4] [5] [6] [7] [8] . A number of issues, such as the amount of virus released and the number of people exposed, need to be considered in order to estimate the impact of a bioterrorist attack with smallpox. However, one key factor in determining the size of an outbreak resulting from such an attack is the transmissibility of smallpox, which can be difficult to estimate. One measure of transmissibility is the effective reproductive rate (R), which is equal to the expected number of infections produced by an infectious host in a real world setting [5, [9] [10] [11] .