Identity and genetic origins : an ethical exploration of the late discovery of adoptive and donor-insemination offspring status

This thesis is an ethical and empirical exploration of the late discovery of genetic origins in two contexts, adoption and sperm donor-assisted conception. This exploration has two interlinked strands of concern. The first is the identification of ‘late discovery’ as a significant issue of concern, deserving of recognition and acknowledgment. The second concerns the ethical implications of late discovery experiences for the welfare of the child. The apparently simple act of recognition of a phenomenon is a precondition to any analysis and critique of it. This is especially important when the phenomenon arises out of social practices that arouse significant debate in ethical and legal contexts. As the new reproductive technologies and some adoption practices remain highly contested, an ethical exploration of this long neglected experience has the potential to offer new insights and perspectives in a range of contexts. It provides an opportunity to revisit developmental debate on the relative merit or otherwise of biological versus social influences, from the perspective of those who have lived this dichotomy in practise. Their experiences are the human face of the effects arising from decisions taken by others to intentionally separate their biological and social worlds, an action which has then been compounded by family and institutional secrecy from birth. This has been accompanied by a failure to ensure that normative standards and values are upheld for them. Following discovery, these factors can be exacerbated by a lack of recognition and acknowledgement of their concerns by family, friends, community and institutions. Late discovery experiences offer valuable insights to inform discussions on the ethical meanings of child welfare, best interests, parental responsibility, duty of care and child identity rights in this and other contexts. They can strengthen understandings of what factors are necessary for a child to be able to live a reasonably happy or worthwhile life.

A parallel cooperative co-evolutionary genetic algorithm for the composite SaaS placement problem in Cloud computing

A composite SaaS (Software as a Service) is a software that is comprised of several software components and data components. The composite SaaS placement problem is to determine where each of the components should be deployed in a cloud computing environment such that the performance of the composite SaaS is optimal. From the computational point of view, the composite SaaS placement problem is a large-scale combinatorial optimization problem. Thus, an Iterative Cooperative Co-evolutionary Genetic Algorithm (ICCGA) was proposed. The ICCGA can find reasonable quality of solutions. However, its computation time is noticeably slow. Aiming at improving the computation time, we propose an unsynchronized Parallel Cooperative Co-evolutionary Genetic Algorithm (PCCGA) in this paper. Experimental results have shown that the PCCGA not only has quicker computation time, but also generates better quality of solutions than the ICCGA.

Association between prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data

Background: Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives: We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results: Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p, 0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7610 24). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions: Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes.

Novel molecular markers of Chlamydia pecorum genetic diversity in the koala (Phascolarctos cinereus)

Background Chlamydia pecorum is an obligate intracellular bacterium and the causative agent of reproductive and ocular disease in several animal hosts including koalas, sheep, cattle and goats. C. pecorum strains detected in koalas are genetically diverse, raising interesting questions about the origin and transmission of this species within koala hosts. While the ompA gene remains the most widely-used target in C. pecorum typing studies, it is generally recognised that surface protein encoding genes are not suited for phylogenetic analysis and it is becoming increasingly apparent that the ompA gene locus is not congruent with the phylogeny of the C. pecorum genome. Using the recently sequenced C. pecorum genome sequence (E58), we analysed 10 genes, including ompA, to evaluate the use of ompA as a molecular marker in the study of koala C. pecorum genetic diversity. Results Three genes (incA, ORF663, tarP) were found to contain sufficient nucleotide diversity and discriminatory power for detailed analysis and were used, with ompA, to genotype 24 C. pecorum PCR-positive koala samples from four populations. The most robust representation of the phylogeny of these samples was achieved through concatenation of all four gene sequences, enabling the recreation of a "true" phylogenetic signal. OmpA and incA were of limited value as fine-detailed genetic markers as they were unable to confer accurate phylogenetic distinctions between samples. On the other hand, the tarP and ORF663 genes were identified as useful "neutral" and "contingency" markers respectively, to represent the broad evolutionary history and intra-species genetic diversity of koala C. pecorum. Furthermore, the concatenation of ompA, incA and ORF663 sequences highlighted the monophyletic nature of koala C. pecorum infections by demonstrating a single evolutionary trajectory for koala hosts that is distinct from that seen in non-koala hosts. Conclusions While the continued use of ompA as a fine-detailed molecular marker for epidemiological analysis appears justified, the tarP and ORF663 genes also appear to be valuable markers of phylogenetic or biogeographic divisions at the C. pecorum intra-species level. This research has significant implications for future typing studies to understand the phylogeny, genetic diversity, and epidemiology of C. pecorum infections in the koala and other animal species.

Persistence of multiple genetic lineages within intra-host populations of Ross River virus

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances

Correlation-based damage detection for complicated truss bridges using multi-layer genetic algorithms

The study presents a multi-layer genetic algorithm (GA) approach using correlation-based methods to facilitate damage determination for through-truss bridge structures. To begin, the structure’s damage-suspicious elements are divided into several groups. In the first GA layer, the damage is initially optimised for all groups using correlation objective function. In the second layer, the groups are combined to larger groups and the optimisation starts over at the normalised point of the first layer result. Then the identification process repeats until reaching the final layer where one group includes all structural elements and only minor optimisations are required to fine tune the final result. Several damage scenarios on a complicated through-truss bridge example are nominated to address the proposed approach’s effectiveness. Structural modal strain energy has been employed as the variable vector in the correlation function for damage determination. Simulations and comparison with the traditional single-layer optimisation shows that the proposed approach is efficient and feasible for complicated truss bridge structures when the measurement noise is taken into account.

Genetic algorithms to schedule container transfers at multimodal terminals

Optimising the container transfer schedule at the multimodal terminals is known to be NP-hard, which implies that the best solution becomes computationally infeasible as problem sizes increase. Genetic Algorithm (GA) techniques are used to reduce container handling/transfer times and ships' time at the port by speeding up handling operations. The GA is chosen due to the relatively good results that have been reported even with the simplest GA implementations to obtain near-optimal solutions in reasonable time. Also discussed, is the application of the model to assess the consequences of increased scheduled throughput time as well as different strategies such as the alternative plant layouts, storage policies and number of yard machines. A real data set used for the solution and subsequent sensitivity analysis is applied to the alternative plant layouts, storage policies and number of yard machines.

A penalty-based grouping genetic algorithm for multiple composite SaaS components clustering in Cloud

Software as a Service (SaaS) in Cloud is getting more and more significant among software users and providers recently. A SaaS that is delivered as composite application has many benefits including reduced delivery costs, flexible offers of the SaaS functions and decreased subscription cost for users. However, this approach has introduced a new problem in managing the resources allocated to the composite SaaS. The resource allocation that has been done at the initial stage may be overloaded or wasted due to the dynamic environment of a Cloud. A typical data center resource management usually triggers a placement reconfiguration for the SaaS in order to maintain its performance as well as to minimize the resource used. Existing approaches for this problem often ignore the underlying dependencies between SaaS components. In addition, the reconfiguration also has to comply with SaaS constraints in terms of its resource requirements, placement requirement as well as its SLA. To tackle the problem, this paper proposes a penalty-based Grouping Genetic Algorithm for multiple composite SaaS components clustering in Cloud. The main objective is to minimize the resource used by the SaaS by clustering its component without violating any constraint. Experimental results demonstrate the feasibility and the scalability of the proposed algorithm.

Energy-efficient virtual machine placement in data centers by genetic algorithm

Server consolidation using virtualization technology has become an important technology to improve the energy efficiency of data centers. Virtual machine placement is the key in the server consolidation. In the past few years, many approaches to the virtual machine placement have been proposed. However, existing virtual machine placement approaches to the virtual machine placement problem consider the energy consumption by physical machines in a data center only, but do not consider the energy consumption in communication network in the data center. However, the energy consumption in the communication network in a data center is not trivial, and therefore should be considered in the virtual machine placement in order to make the data center more energy-efficient. In this paper, we propose a genetic algorithm for a new virtual machine placement problem that considers the energy consumption in both the servers and the communication network in the data center. Experimental results show that the genetic algorithm performs well when tackling test problems of different kinds, and scales up well when the problem size increases.

Early inflammatory and myogenic responses to resistance exercise in the elderly

Introduction and Methods: This study compared changes in myokine and myogenic genes following resistance exercise (3 sets of 12 repetitions of maximal unilateral knee extension) in 20 elderly men (67.8 ± 1.0 years) and 15 elderly women (67.2 ± 1.5 years). Results: Monocyte chemotactic protein (MCP)-1, macrophage inhibitory protein (MIP)-1β, interleukin (IL)-6 and MyoD mRNA increased significantly (P < 0.05), whereas myogenin and myostatin mRNA decreased significantly after exercise in both groups. Macrophage-1 (Mac-1) and MCP-3 mRNA did not change significantly after exercise in either group. MIP-1β, Mac-1 and myostatin mRNA were significantly higher before and after exercise in men compared with women. In contrast, MCP-3 and myogenin mRNA were significantly higher before and after exercise in the women compared with the men. Conclusions: In elderly individuals, gender influences the mRNA expression of certain myokines and growth factors, both at rest and after resistance exercise. These differences may influence muscle regeneration following muscle injury

Wolbachia-mediated resistance to dengue virus infection and death at the cellular level

Dengue is currently the most important arthropod-borne viral disease of humans. Recent work has shown dengue virus displays limited replication in its primary vector, the mosquito Aedes aegypti, when the insect harbors the endosymbiotic bacterium Wolbachia pipientis. Wolbachia-mediated inhibition of virus replication may lead to novel methods of arboviral control, yet the functional and cellular mechanisms that underpin it are unknown.

Australian lungfish (Neoceratodus forsteri: Dipnoi) have low genetic variation at allozyme and mitochondrial DNA loci : a conservation alert?

Genetic variation at allozyme and mitochondrial DNA loci was investigated in the Australian lungfish, Neoceratodus forsteri Krefft 1870. Tissue samples for genetic analysis were taken non-lethally from 278 individuals representing two spatially distinct endemic populations (Mary and Burnett rivers), as well as one population thought to be derived from an anthropogenic translocation in the 1890's (Brisbane river). Two of 24 allozyme loci resolved from muscle tissue were polymorphic. Mitochondrial DNA nucleotide sequence diversity estimated across 2,235 base pairs in each of 40 individuals ranged between 0.000423 and 0.001470 per river. Low genetic variation at allozyme and mitochondrial loci could be attributed to population bottlenecks, possibly induced by Pleistocene aridity. Limited genetic differentiation was detected among rivers using nuclear and mitochondrial markers suggesting that admixture may have occurred between the endemic Mary and Burnett populations during periods of low sea level when the drainages may have converged before reaching the ocean. Genetic data was consistent with the explanation that lungfish were introduced to the Brisbane river from the Mary river. Further research using more variable genetic loci is needed before the conservation status of populations can be determined, particularly as anthropogenic demands on lungfish habitat are increasing. In the interim we recommend a management strategy aimed at conserving existing genetic variation within and between rivers.

Inflammatory cytokine responses to progressive resistance training and supplementation with fortified milk in men aged 50+ years : an 18-month randomized controlled trial

We examined the effects of progressive resistance training (PRT) and supplementation with calcium-vitamin D(3) fortified milk on markers of systemic inflammation, and the relationship between inflammation and changes in muscle mass, size and strength. Healthy men aged 50-79 years (n = 180) participated in this 18-month randomized controlled trial that comprised a factorial 2 x 2 design. Participants were randomized to (1) PRT + fortified milk supplement, (2) PRT, (3) fortified milk supplement, or (4) a control group. Participants assigned to PRT trained 3 days per week, while those in the supplement groups consumed 400 ml day(-1) of milk containing 1,000 mg calcium plus 800 IU vitamin D(3). We collected venous blood samples at baseline, 12 and 18 months to measure the serum concentrations of IL-6, TNF-alpha and hs-CRP. There were no exercise x supplement interactions, but serum IL-6 was 29% lower (95% CI, -62, 0) in the PRT group compared with the control group after 12 months. Conversely, IL-6 was 31% higher (95% CI, -2, 65) in the supplement group compared with the non-supplemented groups after 12 and 18 months. These between-group differences did not persist after adjusting for changes in fat mass. In the PRT group, mid-tibia muscle cross-sectional area increased less in men with higher pre-training inflammation compared with those men with lower inflammation (net difference similar to 2.5%, p < 0.05). In conclusion, serum IL-6 concentration decreased following PRT, whereas it increased after supplementation with fortified milk concomitant with changes in fat mass. Furthermore, low-grade inflammation at baseline restricted muscle hypertrophy following PRT.