Efficiency of parallelisation of genetic algorithms in the data analysis context

Most real-life data analysis problems are difficult to solve using exact methods, due to the size of the datasets and the nature of the underlying mechanisms of the system under investigation. As datasets grow even larger, finding the balance between the quality of the approximation and the computing time of the heuristic becomes non-trivial. One solution is to consider parallel methods, and to use the increased computational power to perform a deeper exploration of the solution space in a similar time. It is, however, difficult to estimate a priori whether parallelisation will provide the expected improvement. In this paper we consider a well-known method, genetic algorithms, and evaluate on two distinct problem types the behaviour of the classic and parallel implementations.

Experimental and numerical investigation of strain-rate dependent mechanical properties of single living cells

The objective of this project is to investigate the strain-rate dependent mechanical behaviour of single living cells using both experimental and numerical techniques. The results revealed that living cells behave as porohyperlastic materials and that both solid and fluid phases within the cells play important roles in their mechanical responses. The research reported in this thesis provides a better understanding of the mechanisms underlying the cellular responses to external mechanical loadings and of the process of mechanical signal transduction in living cells. It would help us to enhance knowledge of and insight into the role of mechanical forces in supporting tissue regeneration or degeneration.

An improved modal strain energy method for structural damage detection, 2D simulation

Structural damage detection using modal strain energy (MSE) is one of the most efficient and reliable structural health monitoring techniques. However, some of the existing MSE methods have been validated for special types of structures such as beams or steel truss bridges which demands improving the available methods. The purpose of this study is to improve an efficient modal strain energy method to detect and quantify the damage in complex structures at early stage of formation. In this paper, a modal strain energy method was mathematically developed and then numerically applied to a fixed-end beam and a three-story frame including single and multiple damage scenarios in absence and presence of up to five per cent noise. For each damage scenario, all mode shapes and natural frequencies of intact structures and the first five mode shapes of assumed damaged structures were obtained using STRAND7. The derived mode shapes of each intact and damaged structure at any damage scenario were then separately used in the improved formulation using MATLAB to detect the location and quantify the severity of damage as compared to those obtained from previous method. It was found that the improved method is more accurate, efficient and convergent than its predecessors. The outcomes of this study can be safely and inexpensively used for structural health monitoring to minimize the loss of lives and property by identifying the unforeseen structural damages.

Genetic characterisation and structural analysis of the O-specific polysaccharide of Yersinia pseudotuberculosis serotype O:1c

Many, but not all, of the current 21 serotypes of Yersinia pseudotuberculosis have been investigated with regard to the chemical structures of their O-specific polysaccharide (OPS) and the genetic basis of their biosynthesis. Completion of the genetics and structures of the remaining serotypes will enhance our understanding of the emerging relationship between genetics and structures within this species. Here, we present a structural and genetic analysis of the Y. pseudotuberculosis serotype O:1c OPS. Our results showed that this OPS has the same backbone as Y. pseudotuberculosis O:2b, but with a 3,6-dideoxy-D-ribo-hexofuranose (paratofuranose, Parf) side-branch instead of a 3,6-dideoxy-D-xylo-hexopyranose (abequopyranose, Abep). The 3'-end of the gene cluster is the same as for O:2b and has the genes for synthesis of the backbone and for processing the completed repeat unit. The 5'-end of the cluster consists of the same genes as O:1b for synthesis of Parf and a related gene for its transfer to the repeating unit backbone.

Structure of the K2 capsule associated with the KL2 gene cluster of Acinetobacter baumannii

The repeat unit structure of the K2 capsule from an extensively antibiotic-resistant Acinetobacter baumannii global clone 2 (GC2) strain was determined. The oligosaccharide contains three simple sugars, d-glucopyranose, d-galatopyranose and N-acetyl-d-galactosamine, and the complex sugar, 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-non-2-ulosonic acid (Pse5Ac7Ac or pseudaminic acid), which has not previously been reported in any A. baumannii capsule. The strain was found to carry all the genes required for the synthesis of the sugars and construction of the K2 structure. The linkages catalyzed by the initiating transferase, three glycosyltransferases and the Wzy polymerase were also predicted. Examination of publicly available A. baumannii genome sequences revealed that the same gene cluster, KL2, often occurs in extensively antibiotic-resistant GC2 isolates and in further strain types. The gene module responsible for the synthesis of pseudaminic acid was also detected in four other K loci. A related module including genes for an acylated relative of pseudaminic acid was also found in two new KL types. A polymerase chain reaction scheme was developed to detect all modules containing genes for sugars based on pseudaminic acid and to specifically detect KL2.

Genome Sequence of Acinetobacter baumannii Strain A1, an Early Example of Antibiotic-Resistant Global Clone 1

Acinetobacter baumannii isolate A1 was recovered in the United Kingdom in 1982 and belongs to global clone 1 (GC1). Here, we present its complete 3.91-Mbp genome sequence, generated via a combination of short-read sequencing (Illumina), long-read sequencing (PacBio), and manual finishing.

Can perceptual indices estimate physiological strain across a range of environments and metabolic workloads when wearing explosive ordnance disposal and chemical protective clothing?

Objective Explosive ordnance disposal (EOD) often requires technicians to wear multiple protective garments in challenging environmental conditions. The accumulative effect of increased metabolic cost coupled with decreased heat dissipation associated with these garments predisposes technicians to high levels of physiological strain. It has been proposed that a perceptual strain index (PeSI) using subjective ratings of thermal sensation and perceived exertion as surrogate measures of core body temperature and heart rate, may provide an accurate estimation of physiological strain. Therefore, this study aimed to determine if the PeSI could estimate the physiological strain index (PSI) across a range of metabolic workloads and environments while wearing heavy EOD and chemical protective clothing. Methods Eleven healthy males wore an EOD and chemical protective ensemble while walking on a treadmill at 2.5, 4 and 5.5 km·h− 1 at 1% grade in environmental conditions equivalent to wet bulb globe temperature (WBGT) 21, 30 and 37 °C. WBGT conditions were randomly presented and a maximum of three randomised treadmill walking trials were completed in a single testing day. Trials were ceased at a maximum of 60-min or until the attainment of termination criteria. A Pearson's correlation coefficient, mixed linear model, absolute agreement and receiver operating characteristic (ROC) curves were used to determine the relationship between the PeSI and PSI. Results A significant moderate relationship between the PeSI and the PSI was observed [r = 0.77; p < 0.001; mean difference = 0.8 ± 1.1 a.u. (modified 95% limits of agreement − 1.3 to 3.0)]. The ROC curves indicated that the PeSI had a good predictive power when used with two, single-threshold cut-offs to differentiate between low and high levels of physiological strain (area under curve: PSI three cut-off = 0.936 and seven cut-off = 0.841). Conclusions These findings support the use of the PeSI for monitoring physiological strain while wearing EOD and chemical protective clothing. However, future research is needed to confirm the validity of the PeSI for active EOD technicians operating in the field.

Microscale consolidation analysis of relaxation behavior of single living chondrocytes subjected to varying strain-rates

Besides the elastic stiffness, the relaxation behavior of single living cells is also of interest of various researchers when studying cell mechanics. It is hypothesized that the relaxation response of the cells is governed by both intrinsic viscoelasticity of the solid phase and fluid-solid interactions mechanisms. There are a number of mechanical models have been developed to investigate the relaxation behavior of single cells. However, there is lack of model enable to accurately capture both of the mechanisms. Therefore, in this study, the porohyperelastic (PHE) model, which is an extension of the consolidation theory, combined with inverse Finite Element Analysis (FEA) technique was used at the first time to investigate the relaxation response of living chondrocytes. This model was also utilized to study the dependence of relaxation behavior of the cells on strain-rates. The stress-relaxation experiments under the various strain-rates were conducted with the Atomic Force Microscopy (AFM). The results have demonstrated that the PHE model could effectively capture the stress-relaxation behavior of the living chondrocytes, especially at intermediate to high strain-rates. Although this model gave some errors at lower strain-rates, its performance was acceptable. Therefore, the PHE model is properly a promising model for single cell mechanics studies. Moreover, it has been found that the hydraulic permeability of living chondrocytes reduced with decreasing of strain-rates. It might be due to the intracellular fluid volume fraction and the fluid pore pressure gradients of chondrocytes were higher when higher strain-rates applied.

Molecular analysis of asymptomatic bacteriuria escherichia coli strain VR50 reveals adaptation to the urinary tract by gene acquisition

Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. © 2013 Springer-Verlag Berlin Heidelberg.

The future for genetic studies in reproduction

Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies(GWAS) have revolutionized gene discovery forcommontraits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases.GWAS 'hits' provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.

Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10(-8)), including rs12700667 on 7p15.2 (P = 1.6 × 10(-9)), rs7521902 near WNT4 (P = 1.8 × 10(-15)), rs10859871 near VEZT (P = 4.7 × 10(-15)), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10(-8)), rs7739264 near ID4 (P = 6.2 × 10(-10)) and rs13394619 in GREB1 (P = 4.5 × 10(-8)). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10(-8)) and rs4141819 on 2p14 (P = 9.2 × 10(-8)). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways.

Different approaches of applying single-objective binary genetic algorithm on the wind farm design

This paper discusses three different ways of applying the single-objective binary genetic algorithm into designing the wind farm. The introduction of different applications is through altering the binary encoding methods in GA codes. The first encoding method is the traditional one with fixed wind turbine positions. The second involves varying the initial positions from results of the first method, and it is achieved by using binary digits to represent the coordination of wind turbine on X or Y axis. The third is the mixing of the first encoding method with another one, which is by adding four more binary digits to represent one of the unavailable plots. The goal of this paper is to demonstrate how the single-objective binary algorithm can be applied and how the wind turbines are distributed under various conditions with best fitness. The main emphasis of discussion is focused on the scenario of wind direction varying from 0° to 45°. Results show that choosing the appropriate position of wind turbines is more significant than choosing the wind turbine numbers, considering that the former has a bigger influence on the whole farm fitness than the latter. And the farm has best performance of fitness values, farm efficiency, and total power with the direction between 20°to 30°.

Molecular genetic investigation of mitochondrial dysfunction in relation to migraine susceptibility

The aim of this research was to assess the role of genetic variation in mitochondrial function and how this relates to migraine pathophysiology. Using our unique Norfolk Island population, a custom in-house next generation sequencing methodology was developed. This data for the first time showed that there is a molecular genetic link between mitochondrial dysfunction and migraine susceptibility. This work has provided the foundation for further studies aimed at utilising the identified markers in improved migraine diagnostic and therapeutic strategies.