Creatine kinase (CK) is a key enzyme in vertebrate excitable tissues. In this research, five conserved residues located on the intra-subunit domain-domain interface were mutated to explore their role in the activity and structural stability of CK. The mutations of Val72 and Gly73 decreased both the activity and stability of CK. The mutations of Cys74 and Val75, which had no significant effect on CK activity and structure, gradually decreased the stability and reactivation of CK. Our results suggested that the mutations might modify the correct positioning of the loop contributing to domain-domain interactions, and result in decreased stability against denaturation.
Shopping malls are densely located in major cities such as Singapore and Hong Kong. Tenants in these shopping malls generate a large number of freight orders to their contracted logistics service providers, who independently plan their own delivery schedules. These uncoordinated deliveries and limited docking capacity jointly cause congestion at the shopping malls. A delivery coordination platform centrally plans the vehicle routes for the logistics service providers and simultaneously schedules the dock time slots at the shopping malls for the delivery orders. Vehicle routing and dock scheduling decisions need to be made jointly against the backdrop of travel time and service time uncertainty and subject to practical operations rules. We model this problem as a two-stage stochastic mixed integer program, develop an adaptive large neighborhood search algorithm that approximates the second stage recourse function using various sample sizes, and examine the associated in-sample and out-of-sample stability. Our numerical study on a testbed of instances based on real data in Singapore demonstrates the value of coordination and the value of stochastic solutions.
In bike-sharing systems, the spatiotemporal imbalance of bike flows leads to shortages of bikes at some locations and overages at some others, depending on the time of the day, resulting in user dissatisfaction. Repositioning needs to be performed timely to deal with the spatiotemporal imbalance and to meet user demand in time. In this paper, we study the dynamic intra-cell repositioning of bikes by a single mover in free-floating bike-sharing systems. Considering that users can drop off bikes almost anywhere in free-floating systems, we study the simultaneous reposition of bikes among gathering points and collection of bikes scattered along the paths between gathering points under stochastic demands at both the gathering points and along the paths. We formulate the problem as a Markov decision process (MDP), design a policy function approximation (PFA) algorithm, and apply the optimal computing budget allocation method (OCBA) to search for the optimal policy parameters. We perform a comprehensive numerical study using test instances constructed based on the real data set of a major free-floating bike-sharing company in China, which demonstrates the outperformance of the proposed PFA policy against the benchmark policies and the practical implications on the value of repositioning and the impact of bike scatteredness.
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