The vehicle routing problem with simultaneous pickup and delivery and handling costs

In this paper we introduce the vehicle routing problem with simultaneous pickup and delivery and handling costs (VRPSPD-H). In the VRPSPD-H, a fleet of vehicles operates from a single depot to service all customers, which have both a delivery and a pickup demand such that all delivery items originate from and all pickup items go to the depot. The items on the vehicles are organized as a single linear stack where only the last loaded item is accessible. Handling operations are required if the delivery items are not the last loaded ones. We implement a heuristic handling policy approximating the optimal decisions for the handling sub-problem, and we propose two bounds on the optimal policy, resulting in two new myopic policies. We show that one of the myopic policies outperforms the other one in all configurations, and that it is competitive with the heuristic handling policy if many routes are required. We propose an adaptive large neighborhood search (ALNS) metaheuristic to solve our problem, in which we embed the handling policies. Computational results indicate that our metaheuristic finds optimal solutions on instances of up to 15 customers. We also compare our ALNS metaheuristic against best solutions on benchmark instances of two special cases, the vehicle routing problem with simultaneous pickup and delivery (VRPSPD) and the traveling salesman problem with pickups, deliveries and handling costs (TSPPD-H), and on two related problems, the vehicle routing problem with divisible pickup and delivery (VRPDPD) and the vehicle routing problem with mixed pickup and delivery (VRPMPD). We find or improve 39 out of 54 best known solutions (BKS) for the VRPSPD, 36 out of 54 BKS for the VRPDPD, 15 out of 21 BKS for the VRPMPD, and 69 out of 80 BKS for the TSPPD-H. Finally, we introduce and analyze solutions for the variations of the VRPDPD and VRPMPD with handling costs – the VRPDPD-H and the VRPMPD-H, respectively

Tandem repeat regions within the Burkholderia pseudomallei genome and their application for high resolution genotyping

BACKGROUND: The facultative, intracellular bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals. We identified and categorized tandem repeat arrays and their distribution throughout the genome of B. pseudomallei strain K96243 in order to develop a genetic typing method for B. pseudomallei. We then screened 104 of the potentially polymorphic loci across a diverse panel of 31 isolates including B. pseudomallei, B. mallei and B. thailandensis in order to identify loci with varying degrees of polymorphism. A subset of these tandem repeat arrays were subsequently developed into a multiple-locus VNTR analysis to examine 66 B. pseudomallei and 21 B. mallei isolates from around the world, as well as 95 lineages from a serial transfer experiment encompassing ~18,000 generations. RESULTS: B. pseudomallei contains a preponderance of tandem repeat loci throughout its genome, many of which are duplicated elsewhere in the genome. The majority of these loci are composed of repeat motif lengths of 6 to 9 bp with 4 to 10 repeat units and are predominately located in intergenic regions of the genome. Across geographically diverse B. pseudomallei and B.mallei isolates, the 32 VNTR loci displayed between 7 and 28 alleles, with Nei's diversity values ranging from 0.47 and 0.94. Mutation rates for these loci are comparable (>10(-5 )per locus per generation) to that of the most diverse tandemly repeated regions found in other less diverse bacteria. CONCLUSION: The frequency, location and duplicate nature of tandemly repeated regions within the B. pseudomallei genome indicate that these tandem repeat regions may play a role in generating and maintaining adaptive genomic variation. Multiple-locus VNTR analysis revealed extensive diversity within the global isolate set containing B. pseudomallei and B. mallei, and it detected genotypic differences within clonal lineages of both species that were identical using previous typing methods. Given the health threat to humans and livestock and the potential for B. pseudomallei to be released intentionally, MLVA could prove to be an important tool for fine-scale epidemiological or forensic tracking of this increasingly important environmental pathogen

Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer

Background Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. Results Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. Conclusion We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer

Pathogen to commensal? Longitudinal within-host population dynamics, evolution, and adaptation during a chronic >16-year Burkholderia pseudomallei infection

Although acute melioidosis is the most common outcome of Burkholderia pseudomallei infection, we have documented a case, P314, where disease severity lessened with time, and the pathogen evolved towards a commensal relationship with the host. In the current study, we used whole-genome sequencing to monitor this long-term symbiotic relationship to better understand B. pseudomallei persistence in P314's sputum despite intensive initial therapeutic regimens. We collected and sequenced 118 B. pseudomallei isolates from P314's airways over a >16-year period, and also sampled the patient's home environment, recovering six closely related B. pseudomallei isolates from the household water system. Using comparative genomics, we identified 126 SNPs in the core genome of the 124 isolates or 162 SNPs/indels when the accessory genome was included. The core SNPs were used to construct a phylogenetic tree, which demonstrated a close relationship between environmental and clinical isolates and detailed within-host evolutionary patterns. The phylogeny had little homoplasy, consistent with a strictly clonal mode of genetic inheritance. Repeated sampling revealed evidence of genetic diversification, but frequent extinctions left only one successful lineage through the first four years and two lineages after that. Overall, the evolution of this population is nonadaptive and best explained by genetic drift. However, some genetic and phenotypic changes are consistent with in situ adaptation. Using a mouse model, P314 isolates caused greatly reduced morbidity and mortality compared to the environmental isolates. Additionally, potentially adaptive phenotypes emerged and included differences in the O-antigen, capsular polysaccharide, motility, and colony morphology. The >13-year co-existence of two long-lived lineages presents interesting hypotheses that can be tested in future studies to provide additional insights into selective pressures, niche differentiation, and microbial adaptation. This unusual melioidosis case presents a rare example of the evolutionary progression towards commensalism by a highly virulent pathogen within a single human host

Stereotypes concerning students with special educational needs: teachers´ beliefs, -expectations and -emotions

Dieses Kapitel geht der Frage nach, ob Lehrer*innenüberzeugungen und -erwartungen je nach sonderpädagogischem Förderbedarf variieren. Außerdem wurde deren Einfluss sowohl auf die Gefühle bei Auseinandersetzung mit der Inklusion von unterschiedlichen Schüler*innen als auch auf die persönliche Bereitschaft, Inklusion umzusetzen, untersucht. Die Studien basieren einerseits auf dem Kontinuum-Modell der Eindrucksbildung und betrachten andererseits das Stereotype-Content-Modell, nach dem Wärme und Kompetenz über 80 % der Unterschiedlichkeit in der Personenwahrnehmung erklären. Die Ergebnisse zeigten, dass Überzeugungen und Erwartungen von der Art des Förderbedarfs beeinflusst werden. Positivere Überzeugungen bezüglich der Schüler*innenmerkmale (Wärme und Kompetenz) und höhere Leistungserwartungen waren hierbei mit positiveren Gefühlen und einer stärker ausgeprägten persönlichen Bereitschaft, die Schüler*innen mit sonderpädagogischem Förderbedarf zu inkludieren, verbunden. Abschließend werden die daraus resultierenden Konsequenzen für die Lehreraus- und weiterbildung abgeleitet und diskutiert