All the recombinant DNA and RVFV were created upon the approval of the Notification of Use by the Institutional Biosafety Committee at UTMB. Figure S1 Plaque phenotypes of MP-12 encoding NSs mutants. VeroE6 cells were infected with indicated virus as 10-fold dilution, and overlaid with 0.6% noble agar containing 5% FBS and 5% Tryptose phosphate broth in MEM as described previously [80] . Second overlay of agar containing 0.011% of neutral red was performed at 3 dpi. Plaques at 4 dpi are shown. (TIF) Figure S2 Titer of MP-12 NSs mutants in MRC-5 cells. Human lung diploid MRC-5 cells were infected with MP-12, rMP12-C13type (C13type) or NSs mutants encoding indicated truncations at an moi of 0.01. At 72 hpi, culture supernatants were collected, and virus titers were measured by plaque assay using VeroE6 cells. Means and standard deviations of 3 independent experiments are shown. **p,0.01, Student's unpaired t-test compared to MP-12. (TIF) Figure S3 Co-infection of MP-12 and MP-12 encoding truncated NSs. VeroE6 cells were mock-infected or infected with a mixture of MP-12 (an moi of 3) and either of rMP12-C13type (C13type) or indicated NSs truncation mutants (an moi of 3). Cells were collected at 16 hpi, and PKR (anti-PKR antibody), NSs and N (anti-RVFV antibody) and b-actin (anti-actin antibody) were detected by Western blot. (TIF) Predictive and Reactive Distribution of Vaccines and Antivirals during Cross-Regional Pandemic Outbreaks As recently pointed out by the Institute of Medicine, the existing pandemic mitigation models lack the dynamic decision support capability. We develop a large-scale simulation-driven optimization model for generating dynamic predictive distribution of vaccines and antivirals over a network of regional pandemic outbreaks. The model incorporates measures of morbidity, mortality, and social distancing, translated into the cost of lost productivity and medical expenses. The performance of the strategy is compared to that of the reactive myopic policy, using a sample outbreak in Fla, USA, with an affected population of over four millions. The comparison is implemented at different levels of vaccine and antiviral availability and administration capacity. Sensitivity analysis is performed to assess the impact of variability of some critical factors on policy performance. The model is intended to support public health policy making for effective distribution of limited mitigation resources. As of July 2010, WHO has reported 501 confirmed human cases of avian influenza A/(H5N1) which resulted in 287 deaths worldwide [1] . At the same time, the statistics for the H1N1 2009 outbreak has so far included 214 countries with a total reported number of infections and deaths of 419,289 and 18,239, respectively [2] . Today, an ominous expectation exists that the next pandemic will be triggered by a highly pathogenic virus, to which there is little or no pre-existing immunity in humans [3] .