DISPATCHING AND RELOCATION OF EMERGENCY VEHICLES ON FREEWAYS: THEORIES AND APPLICATIONS

Resource allocation decisions are made to serve the current emergency without knowing which future emergency will be occurring. Different ordered combinations of emergencies result in different performance outcomes. Even though future decisions can be anticipated with scenarios, previous models follow an assumption that events over a time interval are independent. This dissertation follows an assumption that events are interdependent, because speed reduction and rubbernecking due to an initial incident provoke secondary incidents. The misconception that secondary incidents are not common has resulted in overlooking a look-ahead concept. This dissertation is a pioneer in relaxing the structural assumptions of independency during the assignment of emergency vehicles. When an emergency is detected and a request arrives, an appropriate emergency vehicle is immediately dispatched. We provide tools for quantifying impacts based on fundamentals of incident occurrences through identification, prediction, and interpretation of secondary incidents. A proposed online dispatching model minimizes the cost of moving the next emergency unit, while making the response as close to optimal as possible. Using the look-ahead concept, the online model flexibly re-computes the solution, basing future decisions on present requests. We introduce various online dispatching strategies with visualization of the algorithms, and provide insights on their differences in behavior and solution quality. The experimental evidence indicates that the algorithm works well in practice. After having served a designated request, the available and/or remaining vehicles are relocated to a new base for the next emergency. System costs will be excessive if delay regarding dispatching decisions is ignored when relocating response units. This dissertation presents an integrated method with a principle of beginning with a location phase to manage initial incidents and progressing through a dispatching phase to manage the stochastic occurrence of next incidents. Previous studies used the frequency of independent incidents and ignored scenarios in which two incidents occurred within proximal regions and intervals. The proposed analytical model relaxes the structural assumptions of Poisson process (independent increments) and incorporates evolution of primary and secondary incident probabilities over time. The mathematical model overcomes several limiting assumptions of the previous models, such as no waiting-time, returning rule to original depot, and fixed depot. The temporal locations flexible with look-ahead are compared with current practice that locates units in depots based on Poisson theory. A linearization of the formulation is presented and an efficient heuristic algorithm is implemented to deal with a large-scale problem in real-time.

The role of intracellular calcium perturbations in muscle damage and dysfunction in mouse models of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. DMD is clinically characterized by severe, progressive and irreversible loss of muscle function, in which most patients lose the ability to walk by their early teens and die by their early 20’s. Impaired intracellular calcium (Ca2+) regulation and activation of cell degradation pathways have been proposed as key contributors to DMD disease progression. This dissertation research consists of three studies investigating the role of intracellular Ca2+ in skeletal muscle dysfunction in different mouse models of DMD. Study one evaluated the role of Ca2+-activated enzymes (proteases) that activate protein degradation in excitation-contraction (E-C) coupling failure following repeated contractions in mdx and dystrophin-utrophin null (mdx/utr-/-) mice. Single muscle fibers from mdx/utr-/- mice had greater E-C coupling failure following repeated contractions compared to fibers from mdx mice. Moreover, protease inhibition during these contractions was sufficient to attenuate E-C coupling failure in muscle fibers from both mdx and mdx/utr-/- mice. Study two evaluated the effects of overexpressing the Ca2+ buffering protein sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 (SERCA1) in skeletal muscles from mdx and mdx/utr-/- mice. Overall, SERCA1 overexpression decreased muscle damage and protected the muscle from contraction-induced injury in mdx and mdx/utr-/- mice. In study three, the cellular mechanisms underlying the beneficial effects of SERCA1 overexpression in mdx and mdx/utr-/- mice were investigated. SERCA1 overexpression attenuated calpain activation in mdx muscle only, while partially attenuating the degradation of the calpain target desmin in mdx/utr-/- mice. Additionally, SERCA1 overexpression decreased the SERCA-inhibitory protein sarcolipin in mdx muscle but did not alter levels of Ca2+ regulatory proteins (parvalbumin and calsequestrin) in either dystrophic model. Lastly, SERCA1 overexpression blunted the increase in endoplasmic reticulum stress markers Grp78/BiP in mdx mice and C/EBP homologous protein (CHOP) in mdx and mdx/utr-/- mice. Overall, findings from the studies presented in this dissertation provide new insight into the role of Ca2+ in muscle dysfunction and damage in different dystrophic mouse models. Further, these findings support the overall strategy for improving intracellular Ca2+ control for the development of novel therapies for DMD.