A choice function hyper-heuristic framework for the allocation of maintenance tasks in Danish railways

This work has been partially funded by the DAASE project, EPSRC programme grant EP/J017515/1

A hybrid Constraint Programming/Mixed Integer Programming framework for the preventive signaling maintenance crew scheduling problem

This research has been carried out as part of the PhD research project funded by Technical University of Denmark and Banedanmark company which is responsible for the operation and maintenance of the Danish railway network. This work has been partially funded by the DAASE project, EPSRC programme grant EP/J017515/1

Searching for configurations in clone evaluation - A replication study

Clone detection is the process of finding duplicated code within a software code base in an automated manner. It is useful in several areas of software development such as code quality analysis, bug detection, and program understanding.We replicate a study of a geneticalgorithm based framework that optimises parameters for clone agreement (EvaClone). We apply the framework to 14 releases of Mockito, a Java mocking framework. We observe that the optimised parameters outperform the tools’ default parameters in term of clone agreement by 19.91% to 66.43 %. However, the framework gives undesirable results in term of clone quality. EvaClone either maximises or minimises a number of clones in order to achieve the highest agreement resulting in more false positives or false negatives introduced consequently

A Hyper-heuristic for Multi-objective Integration and Test Ordering in Google Guava

Integration testing seeks to find communication problems between different units of a software system. As the order in which units are considered can impact the overall effort required to perform integration testing, deciding an appropriate sequence to integrate and test units is vital. Here we apply a multi-objective hyper-heuristic set within an NSGA-II framework to the Integration and Test Order Problem (ITO) for Google Guava, a set of open-source common libraries for Java. Our results show that an NSGA-II based hyper-heuristic employing a simplified version of Choice Function heuristic selection, outperforms standard NSGA-II for this problem

Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

Automated generation of constructive ordering heuristics for educational timetabling

Construction heuristics play an important role in solving combinatorial optimization problems. These heuristics are usually used to create an initial solution to the problem which is improved using optimization techniques such as metaheuristics. For examination timetabling and university course timetabling problems essentially graph colouring heuristics have been used for this purpose. The process of deriving heuristics manually for educational timetabling is a time consuming task. Furthermore, according to the no free lunch theorem different heuristics will perform well for different problems and problem instances. Hence, automating the induction of construction heuristics will reduce the man hours involved in creating such heuristics, allow for the derivation of problem specific heuristics and possibly result in the derivation of heuristics that humans have not thought of. This paper presents generation construction hyper-heuristics for educational timetabling. The study investigates the automatic induction of two types of construction heuristics, namely, arithmetic heuristics and hierarchical heuristics. Genetic programming is used to evolve arithmetic heuristics. Genetic programming, genetic algorithms and the generation of random heuristic combinations is examined for the generation of hierarchical heuristics. The hyper-heuristics generating both types of heuristics are applied to the examination timetabling and the curriculum based university course timetabling problems. The evolved heuristics were found to perform much better than the existing graph colouring heuristics used for this domain. Furthermore, it was found that the while the arithmetic heuristics were more effective for the examination timetabling problem, the hierarchical heuristics produced better results than the arithmetic heuristics for the curriculum based course timetabling problem. Genetic algorithms proved to be the most effective at inducing hierarchical heuristics

Correcting the Site Frequency Spectrum for Divergence-Based Ascertainment

Comparative genomics based on sequenced referenced genomes is essential to hypothesis generation and testing within population genetics. However, selection of candidate regions for further study on the basis of elevated or depressed divergence between species leads to a divergence-based ascertainment bias in the site frequency spectrum within selected candidate loci. Here, a method to correct this problem is developed that obtains maximum-likelihood estimates of the unascertained allele frequency distribution using numerical optimization. I show how divergence-based ascertainment may mimic the effects of natural selection and offer correction formulae for performing proper estimation into the strength of selection in candidate regions in a maximum-likelihood setting

Performance of selection hyper-heuristics on the extended HyFlex domains

Selection hyper-heuristics perform search over the space of heuristics by mixing and controlling a predefined set of low level heuristics for solving computationally hard combinatorial optimisation problems. Being reusable methods, they are expected to be applicable to multiple problem domains, hence performing well in cross-domain search. HyFlex is a general purpose heuristic search API which separates the high level search control from the domain details enabling rapid development and performance comparison of heuristic search methods, particularly hyper-heuristics. In this study, the performance of six previously proposed selection hyper-heuristics are evaluated on three recently introduced extended HyFlex problem domains, namely 0–1 Knapsack, Quadratic Assignment and Max-Cut. The empirical results indicate the strong generalising capability of two adaptive selection hyper-heuristics which perform well across the ‘unseen’ problems in addition to the six standard HyFlex problem domains

Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system