A Large Neighbourhood Search Metaheuristic for the Contagious Disease Testing Problem.

In late 2019 a new coronavirus disease (COVID-19) emerged, causing a global pandemic within only a few weeks. A crucial factor in the public health response to pandemics is achieving a short turnaround time between a potential case becoming known, specimen collection and availability of a test result. In this article we address a logistics problem that arises in the context of testing potential cases. We assume that specimens can be collected in two ways: either by means of a mobile test-team or by means of a stationary test-team in a test-centre. After the specimens have been collected they must be delivered to a laboratory in order to be analysed. The problem we address aims at deciding how many test-centres to open and where, how many mobile test-teams to use, which suspected cases to assign to a test-centre and which to visit with a mobile test-team, which specimen to assign to which laboratory, and planning the routes of the mobile test-teams. The objective is to minimise the total cost of opening test-centres and routing mobile test-teams. We introduce this new problem, which we call the contagious disease testing problem (CDTP), and present a mixed-integer linear-programming formulation for it. We propose a large neighbourhood search metaheuristic for solving the CDTP and present an extensive computational study to illustrate its performance. Furthermore, we give managerial insights regarding COVID-19 test logistics, derived from problem instances based on real world data.

Safe and secure vehicle routing: a survey on minimization of risk exposure.

Safe and secure vehicle routing problems refer to the transportation of dangerous (e.g., flammable liquids) or valuable goods (e.g., cash), the surveillance of streets (e.g., police patrols) or other areas (e.g., those within a factory or building), and the response to sudden incidents (e.g., robberies or street disruptions). It thus covers a multitude of models and methods with each having its own objective and constraints, such as unpredictability or risk. We review and classify literature in this field and thereby identify a starting point for researchers in this evolving and practically relevant field. Our study reveals that there are 82 articles that cover aspects related to safe and secure routing, a majority of which were published in the last five years. We classify the articles into five main categories: (i) transportation of hazardous materials, (ii) patrol routing, (iii) cash-in-transit, (iv) dissimilar routing problems, and (v) modeling of multi-graphs. Categories (i)-(iv) elaborate on the problem studied, while (v) provides a general concept based on road network characteristics most commonly found in safe and secure routing problems. Relevant methods and instances, along with their similarities and dissimilarities, have also been discussed in the paper. Furthermore, specific problem characteristics and future research directions are identified.

Secure and efficient routing on nodes, edges, and arcs of simple-graphs and of multi-graphs.

Many security companies offer patrolling services, such that guards inspect facilities or streets on a regular basis. Patrolling routes should be cost efficient, but the inspection patterns should not be predictable for offenders. We introduce this setting as a multi-objective periodic mixed capacitated general routing problem with objectives being cost minimization and route inconsistency maximization. The problem is transformed into an asymmetric capacitated vehicle routing problem, on both a simple-graph and a multi-graph; and three multi-objective frameworks using adaptive large neighborhood search are implemented to solve it. As tests with both artificial and real-world instances show that some frameworks perform better for some indicators, a hybrid search procedure, combining two of them, is developed and benchmarked against the individual solution methods. Generally, results indicate that considering more than one shortest path between nodes, can significantly increase solution quality for smaller instances, but is quickly becoming a detriment for larger instances.

Solving routing problems with pairwise synchronization constraints.

Pairwise route synchronization constraints are commonly encountered in the field of service technician routing and scheduling and in the area of mobile care. Pairwise route synchronization refers to constraints that require that two technicians or home care workers visit the same location at exactly the same time. We consider constraints of this type in the context of the well-known vehicle routing problem with time windows and a generic service technician routing and scheduling problem. Different approaches for dealing with the problem of pairwise route synchronization are compared and several ways of integrating a synchronization component into a metaheuristic algorithm tailored to the original problems are analyzed. When applied to benchmark instances from the literature, our algorithm matches almost all available optimal values and it produces several new best results for the remaining instances.

The school bus routing and scheduling problem with transfers.

In this article, we study the school bus routing and scheduling problem with transfers arising in the field of nonperiodic public transportation systems. It deals with the transportation of pupils from home to their school in the morning taking the possibility that pupils may change buses into account. Allowing transfers has several consequences. On the one hand, it allows more flexibility in the bus network structure and can, therefore, help to reduce operating costs. On the other hand, transfers have an impact on the service level: the perceived service quality is lower due to the existence of transfers; however, at the same time, user ride times may be reduced and, thus, transfers may also have a positive impact on service quality. The main objective is the minimization of the total operating costs. We develop a heuristic solution framework to solve this problem and compare it with two solution concepts that do not consider transfers. The impact of transfers on the service level in terms of time loss (or user ride time) and the number of transfers is analyzed. Our results show that allowing transfers reduces total operating costs significantly while average and maximum user ride times are comparable to solutions without transfers. © 2015 Wiley Periodicals, Inc. NETWORKS, Vol. 65(2), 180-203 2015.

The artefacts of radiochromic film dosimetry with flatbed scanners and their causation by light scattering from radiation-induced polymers.

Optical experiments and theoretical considerations have been undertaken in order to understand the causes of the 'orientation effect' and the 'parabola effect', the artefacts impairing the desired light absorption measurement on radiochromic EBT3 films with flatbed scanners. EBT3 films exposed to doses up to 20.9 Gy were scanned with an Epson Expression 10000XL flatbed scanner in landscape and portrait orientation. The horizontally and vertically polarized light components of the scanner were determined, and another Epson Expression 10000XL flatbed scanner was disassembled to examine its optical components. The optical properties of exposed and unexposed EBT3 films were studied with incident polarized and unpolarized white light, and the transmitted red light was investigated for its polarization and scattering properties including the distribution of the scattering angles. Neutral density filters were studied for comparison. Guidance was sought from the theory of light scattering from rod-like macromolecular structures. The drastic dose-dependent variation of the transmitted total light current as function of the orientation of front and rear polarizers, interpreted by light scattering theory, shows that the radiation-induced polymerization of the monomers of EBT3 films produces light scattering oscillators preferably polarized at right angles with the coating direction of the film. The directional distribution of the scattered light is partly anisotropic, with a preferred scattering plane at right angles with the coating direction, indicating light scattering from stacks of coherently vibrating oscillators piled up along the monomer crystals. The polyester carrier film also participates in these effects. The 'orientation' and 'parabola' artefacts due to flatbed scanning of radiochromic films can be explained by the interaction of the polarization-dependent and anisotropic light scattering from exposed and unexposed EBT3 films with the quantitative difference between the scanner's horizontally and vertically polarized light supply and with the limited directional acceptance of the scanner's light recording system.

Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152).

A series of compounds were designed and synthesized as antagonists of cIAP1/2, ML-IAP, and XIAP based on the N-terminus, AVPI, of mature Smac. Compound 1 (GDC-0152) has the best profile of these compounds; it binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with K(i) values of 28, 14, 17, and 43 nM, respectively. These compounds promote degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Compound 1 inhibits tumor growth when dosed orally in the MDA-MB-231 breast cancer xenograft model. Compound 1 was advanced to human clinical trials, and it exhibited linear pharmacokinetics over the dose range (0.049 to 1.48 mg/kg) tested. Mean plasma clearance in humans was 9 ± 3 mL/min/kg, and the volume of distribution was 0.6 ± 0.2 L/kg.

Ambulance location and relocation problems with time-dependent travel times.

EMERGENCY SERVICE PROVIDERS ARE FACING THE FOLLOWING PROBLEM: how and where to locate vehicles in order to cover potential future demand effectively. Ambulances are supposed to be located at designated locations such that in case of an emergency the patients can be reached in a time-efficient manner. A patient is said to be covered by a vehicle if (s)he can be reached by an ambulance within a predefined time limit. Due to variations in speed and the resulting travel times it is not sufficient to solve the static ambulance location problem once using fixed average travel times, as the coverage areas themselves change throughout the day. Hence we developed a multi-period version, taking into account time-varying coverage areas, where we allow vehicles to be repositioned in order to maintain a certain coverage standard throughout the planning horizon. We have formulated a mixed integer program for the problem at hand, which tries to optimize coverage at various points in time simultaneously. The problem is solved metaheuristically using variable neighborhood search. We show that it is essential to consider time-dependent variations in travel times and coverage respectively. When ignoring them the resulting objective will be overestimated by more than 24%. By taking into account these variations explicitly the solution on average can be improved by more than 10%.

Determining location and size of medical departments in a hospital network: a multiobjective decision support approach.

Decisions on the location and size of medical departments in a given hospital network are prime examples of priority setting in health care, which is an issue of growing political importance. As such decisions are regularly characterized by multiple and often conflicting objectives in real-life, this paper integrates the fields of hospital planning and multiobjective decision support. The proposed two-phase solution procedure for our corresponding mathematical programming model does not require a priori preference information. Instead, it seeks efficient solutions by means of multiobjective tabu search in the first phase, while applying clustering in the second phase to allow the decision makers to interactively explore the solution space until the "best" configuration is determined. The real-world applicability of our approach is illustrated through a numerical example based on hospital data from Germany.

The kinesin-associated protein UNC-76 is required for axonal transport in the Drosophila nervous system.

Kinesin-I is essential for the transport of membrane-bound organelles in neural and nonneural cells. However, the means by which kinesin interacts with its intracellular cargoes, and the means by which kinesin-cargo interactions are regulated in response to cellular transport requirements are not fully understood. The C terminus of the Drosophila kinesin heavy chain (KHC) was used in a two-hybrid screen of a Drosophila cDNA library to identify proteins that bind specifically to the kinesin tail domain. UNC-76 is an evolutionarily conserved cytosolic protein that binds to the tail domain of KHC in two-hybrid and copurification assays, indicating that kinesin and UNC-76 form a stable complex in vivo. Loss of Drosophila Unc-76 function results in locomotion and axonal transport defects reminiscent of the phenotypes observed in kinesin mutants, suggesting that UNC-76 is required for kinesin-dependent axonal transport. Unc-76 exhibits dosage-sensitive genetic relationships with Khc and Kinesin light chain mutations, further supporting the hypothesis that UNC-76 and kinesin-I work in a common transport pathway. Given the interaction of FEZ1, the mammalian homolog of UNC-76, with protein kinase Czeta, and the role of FEZ1 in axon outgrowth, we propose that UNC-76 helps integrate kinesin activity in response to transport requirements in axons.