Building resilience into today’s complex infrastructures is critical to the daily functioning of society and its ability to withstand and recover from natural disasters, epidemics, and cyber-threats. This study proposes quantitative measures that capture and implement the definition of engineering resilience advanced by the National Academy of Sciences. The approach is applicable across physical, information, and social domains. It evaluates the critical functionality, defined as a performance function of time set by the stakeholders. Critical functionality is a source of valuable information, such as the integrated system resilience over a time interval, and its robustness. The paper demonstrates the formulation on two classes of models: 1) multi-level directed acyclic graphs, and 2) interdependent coupled networks. For both models synthetic case studies are used to explore trends. For the first class, the approach is also applied to the Linux operating system. Results indicate that desired resilience and robustness levels are achievable by trading off different design parameters, such as redundancy, node recovery time, and backup supply available. The nonlinear relationship between network parameters and resilience levels confirms the utility of the proposed approach, which is of benefit to analysts and designers of complex systems and networks.

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The airport flight-to-gate assignment problem is solved using two methods: (1) a linear programming relaxation of an integer program formulation and (2) a heuristic. The objective is to minimize passenger walking distances within the airport terminal area through a judicious gate assignment policy. An actual flight schedule for an average day at Toronto International Airport is used to compare existing walking distances, obtained from the original assignment, with results from the two methods. The results indicated that the original assignment had a 32% higher average per passenger walking distance than the minimum possible distance given by the LP solution. The heuristic’s performance was near optimal; it gave an average walking distance which was only 3.9% greater than the minimum. Computation times for the heuristic are 3.4 CPU seconds per run, while the linear program consumes 386 seconds per run on an IBM 370/168. In addition, if the heuristic is solved first and its solution is used as an initial feasible basis for the LP relaxation of the IP, the total CPU used to obtain optimality is reduced to 42 seconds.

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Our understanding of paracrine and epigenetic control of trophectoderm (TE) differentiation is limited by available models of preimplantation human development. Simple, defined media for selective TE differentiation of human embryonic stem cells (hESCs) were developed, enabling mechanistic studies of early placental development. Paracrine requirements of preimplantation human development were evaluated with hESCs by measuring lineage-specific transcription factor expression levels in single cells and morphological transformation in response to selected paracrine and epigenetic modulators. Bone morphogenic protein 4 (BMP4) addition to feeder-free pluripotent stem cells on matrigel frequently formed CDX2-positive TE. However, BMP4 or activin A inhibition alone also produced a mix of mesoderm and extraembryonic endoderm under these conditions. Further, BMP4 failed to form TE from adherent hESC maintained in standard feeder-dependent monolayers. Given that the efficiency and selectivity of BMP4-induced TE depended on medium components, we developed a basal medium containing insulin and heparin. In this medium, BMP4 induction of TE was dose dependent and with activin A inhibition by SB431542 (SB), approached 100% of cells. This paracrine stimulation of pluripotent cells transformed colony morphology from a cuboidal to squamous epithelium quantitatively on day 3, and produced significant multinucleated syncytiotrophoblasts by day 8. Addition of trichostatin A, a histone deacetylase (HDAC) inhibitor, reduced HDAC3, histone H3K9 methylation, and slowed differentiation in a dosedependent manner. Modulators of BMP4-or HDAC-dependent signaling might adversely influence the timing and viability of early blastocyst developed in vitro. Since blastocyst development is synchronized to uterine receptivity, epigenetic regulators of TE differentiation might adversely affect implantation in vivo.

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