Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

Farmscape online : participatory design of internet meetings with farmers

This paper presents aspects of a longitudinal study in the design and practice of Internet meetings between farmer their advisors and researchers in rural Australia. It reports on the use of Microsoft NetMeeting (NM) by a group of agricultural researchers from Australia's CSIRO (Commonwealth Scientific and Industrial Research Organisation) for regular meetings, over nine years, with farmers and the commercial advisers. It describes lessons drawn from this experience about the conditions under which telecollaborative tools, such as NM and video conferencing, are likely to be both useful and used.

A genetic algorithm for the multi-source and multi-sink minimum vertex cut problem and its applications

We present a new penalty-based genetic algorithm for the multi-source and multi-sink minimum vertex cut problem, and illustrate the algorithm’s usefulness with two real-world applications. It is proved in this paper that the genetic algorithm always produces a feasible solution by exploiting some domain-specific knowledge. The genetic algorithm has been implemented on the example applications and evaluated to show how well it scales as the problem size increases.

QoS-Based Web Service Scheduling Accommodating Inter-Service Dependencies Using Minimal-Conflict Hill-Climbing Repair Genetic Algorithm

In the filed of semantic grid, QoS-based Web service scheduling for workflow optimization is an important problem.However, in semantic and service rich environment like semantic grid, the emergence of context constraints on Web services is very common making the scheduling consider not only quality properties of Web services, but also inter service dependencies which are formed due to the context constraints imposed on Web services. In this paper, we present a repair genetic algorithm, namely minimal-conflict hill-climbing repair genetic algorithm, to address scheduling optimization problems in workflow applications in the presence of domain constraints and inter service dependencies. Experimental results demonstrate the scalability and effectiveness of the genetic algorithm.

A Penalty-based Genetic Algorithm for QoS-AwareWeb Service Composition with Inter-Service Dependencies and Conflicts

In Web service based systems, new value-added Web services can be constructed by integrating existing Web services. A Web service may have many implementations, which are functionally identical, but have different Quality of Service (QoS) attributes, such as response time, price, reputation, reliability, availability and so on. Thus, a significant research problem in Web service composition is how to select an implementation for each of the component Web services so that the overall QoS of the composite Web service is optimal. This is so called QoS-aware Web service composition problem. In some composite Web services there are some dependencies and conflicts between the Web service implementations. However, existing approaches cannot handle the constraints. This paper tackles the QoS-aware Web service composition problem with inter service dependencies and conflicts using a penalty-based genetic algorithm (GA). Experimental results demonstrate the effectiveness and the scalability of the penalty-based GA.

Unsupervised speaker adaptation for telephone call transcription

The use of the PC and Internet for placing telephone calls will present new opportunities to capture vast amounts of un-transcribed speech for a particular speaker. This paper investigates how to best exploit this data for speaker-dependent speech recognition. Supervised and unsupervised experiments in acoustic model and language model adaptation are presented. Using one hour of automatically transcribed speech per speaker with a word error rate of 36.0%, unsupervised adaptation resulted in an absolute gain of 6.3%, equivalent to 70% of the gain from the supervised case, with additional adaptation data likely to yield further improvements. LM adaptation experiments suggested that although there seems to be a small degree of speaker idiolect, adaptation to the speaker alone, without considering the topic of the conversation, is in itself unlikely to improve transcription accuracy.

Channel tracking algorithms for highly efficient wireless broadband communications in rural areas

High-speed broadband internet access is widely recognised as a catalyst to social and economic development, having a significant impact on global economy. Rural Australia’s inherent dispersed population over a large geographical area make the delivery of efficient, well-maintained and cost-effective internet a challenging task. The novel and highly-efficient Multi-User-Single-Antenna for MIMO (MUSA-MIMO) broadband wireless communication technology can effectively be used to deliver wireless broadband access to rural areas. This research aims to develop for the first time, an efficient and accurate algorithm for the tracking and prediction of Channel State Information (CSI) at the transmitter, by characterising time variation effects of the wireless communication channel on the performance of a highly-efficient MUSA-MIMO technology particularly suited for rural communities, improving their quality of life and economic prosperity.

QoS-oriented sesource allocation and scheduling of multiple composite web services in a hybrid cloud using a random-key genetic algorithm

In cloud computing resource allocation and scheduling of multiple composite web services is an important challenge. This is especially so in a hybrid cloud where there may be some free resources available from private clouds but some fee-paying resources from public clouds. Meeting this challenge involves two classical computational problems. One is assigning resources to each of the tasks in the composite web service. The other is scheduling the allocated resources when each resource may be used by more than one task and may be needed at different points of time. In addition, we must consider Quality-of-Service issues, such as execution time and running costs. Existing approaches to resource allocation and scheduling in public clouds and grid computing are not applicable to this new problem. This paper presents a random-key genetic algorithm that solves new resource allocation and scheduling problem. Experimental results demonstrate the effectiveness and scalability of the algorithm.

Multiple camera management using wide baseline matching

Camera calibration information is required in order for multiple camera networks to deliver more than the sum of many single camera systems. Methods exist for manually calibrating cameras with high accuracy. Manually calibrating networks with many cameras is, however, time consuming, expensive and impractical for networks that undergo frequent change. For this reason, automatic calibration techniques have been vigorously researched in recent years. Fully automatic calibration methods depend on the ability to automatically find point correspondences between overlapping views. In typical camera networks, cameras are placed far apart to maximise coverage. This is referred to as a wide base-line scenario. Finding sufficient correspondences for camera calibration in wide base-line scenarios presents a significant challenge. This thesis focuses on developing more effective and efficient techniques for finding correspondences in uncalibrated, wide baseline, multiple-camera scenarios. The project consists of two major areas of work. The first is the development of more effective and efficient view covariant local feature extractors. The second area involves finding methods to extract scene information using the information contained in a limited set of matched affine features. Several novel affine adaptation techniques for salient features have been developed. A method is presented for efficiently computing the discrete scale space primal sketch of local image features. A scale selection method was implemented that makes use of the primal sketch. The primal sketch-based scale selection method has several advantages over the existing methods. It allows greater freedom in how the scale space is sampled, enables more accurate scale selection, is more effective at combining different functions for spatial position and scale selection, and leads to greater computational efficiency. Existing affine adaptation methods make use of the second moment matrix to estimate the local affine shape of local image features. In this thesis, it is shown that the Hessian matrix can be used in a similar way to estimate local feature shape. The Hessian matrix is effective for estimating the shape of blob-like structures, but is less effective for corner structures. It is simpler to compute than the second moment matrix, leading to a significant reduction in computational cost. A wide baseline dense correspondence extraction system, called WiDense, is presented in this thesis. It allows the extraction of large numbers of additional accurate correspondences, given only a few initial putative correspondences. It consists of the following algorithms: An affine region alignment algorithm that ensures accurate alignment between matched features; A method for extracting more matches in the vicinity of a matched pair of affine features, using the alignment information contained in the match; An algorithm for extracting large numbers of highly accurate point correspondences from an aligned pair of feature regions. Experiments show that the correspondences generated by the WiDense system improves the success rate of computing the epipolar geometry of very widely separated views. This new method is successful in many cases where the features produced by the best wide baseline matching algorithms are insufficient for computing the scene geometry.

Beyond statistical procedures for predictive modelling: Data mining algorithms and support for university research at QUT

In a seminal data mining article, Leo Breiman [1] argued that to develop effective predictive classification and regression models, we need to move away from the sole dependency on statistical algorithms and embrace a wider toolkit of modeling algorithms that include data mining procedures. Nevertheless, many researchers still rely solely on statistical procedures when undertaking data modeling tasks; the sole reliance on these procedures has lead to the development of irrelevant theory and questionable research conclusions ([1], p.199). We will outline initiatives that the HPC & Research Support group is undertaking to engage researchers with data mining tools and techniques; including a new range of seminars, workshops, and one-on-one consultations covering data mining algorithms, the relationship between data mining and the research cycle, and limitations and problems with these new algorithms. Organisational limitations and restrictions to these initiatives are also discussed.

Teaching parallel computing concepts with a desktop computer

Parallel computing is currently used in many engineering problems. However, because of limitations in curriculum design, it is not always possible to offer students specific formal teaching in this topic. Furthermore, parallel machines are still too expensive for many institutions. The latest microprocessors, such as Intel’s Pentium III and IV, embody single instruction multiple-data (SIMD) type parallel features, which makes them a viable solution for introducing parallel computing concepts to students. Final year projects have been initiated utilizing SSE (streaming SIMD extensions) features and it has been observed that students can easily learn parallel programming concepts after going through some programming exercises. They can now experiment with parallel algorithms on their own PCs at home. Keywords

From social butterfly to engaged citizen: Urban informatics, social media, ubiquitous computing, and mobile technology to support citizen engagement

Web applications such as blogs, wikis, video and photo sharing sites, and social networking systems have been termed ‘Web 2.0’ to highlight an arguably more open, collaborative, personalisable, and therefore more participatory internet experience than what had previously been possible. Giving rise to a culture of participation, an increasing number of these social applications are now available on mobile phones where they take advantage of device-specific features such as sensors, location and context awareness. This international volume of book chapters will make a contribution towards exploring and better understanding the opportunities and challenges provided by tools, interfaces, methods and practices of social and mobile technology that enable participation and engagement. It brings together an international group of academics and practitioners from a diverse range of disciplines such as computing and engineering, social sciences, digital media and human-computer interaction to critically examine a range of applications of social and mobile technology, such as social networking, mobile interaction, wikis, twitter, blogging, virtual worlds, shared displays and urban sceens, and their impact to foster community activism, civic engagement and cultural citizenship.

Enhancing the use of Internet and Web services for quality learning : an action research

Internet and Web services have been used in both teaching and learning and are gaining popularity in today’s world. E-Learning is becoming popular and considered the latest advance in technology based learning. Despite the potential advantages for learning in a small country like Bhutan, there is lack of eServices at the Paro College of Education. This study investigated students’ attitudes towards online communities and frequency of access to the Internet, and how students locate and use different sources of information in their project tasks. Since improvement was at the heart of this research, an action research approach was used. Based on the idea of purposeful sampling, a semi-structured interview and observations were used as data collection instruments. 10 randomly selected students (5 girls and 5 boys) participated in this research as the controlled group. The study findings indicated that there is a lack of educational information technology services, such as e-learning at the college. Internet connection being very slow was the main barrier to learning using e-learning or accessing Internet resources. There is a strong relationship between the quality of written task and the source of the information, and between Web searching and learning. The source of information used in assignments and project work is limited to books in the library which are often outdated and of poor quality. Project tasks submitted by most of the students were of poor quality.