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.

Mobile communications : a study of factors influencing consumer use of m-services

New mobile digital communication technologies present opportunities for advertisers to capitalize on the evolving relationships of consumers with their mobile devices and their desire to access enhanced information services while mobile (m-services). Consumers already use mobile devices (cell phones, personal mobile digital assistants) for traditional phone calls and message handling (e.g., Kalakota and Robinson, 2002; Sullivan Mort and Drennan, 2002). The combination of rapidly developing mobile digital technology and high uptake rates of mobile devices presents enormous potential for delivery of m-services through these devices (Bitner, Brown, and Meuter, 2000). M-services encompass a wide variety of types including the ability to trade stock, to book theater and movie tickets while accessing seating plans online, to send and receive text and pictures, and receive personalized direct advertising such as alerts for shopping bargains. Marketing communications, and specifically advertising, may be delivered as an m-service and termed m-services advertising, forming part of the broader category of m-services. However, advertising research has not yet addressed the area of m-services and needs to do so to be able to take advantage of the advanced interactivity (Yadav and Varadarajan, 2005) of mobile communication devices. Such advertising research is likely to help develop open attitudes and responses to new business models as has been advocated for other new technology such as advanced television (Tauder, 2005). In this article, we model the factors influencing the use of m-services, in the context of consumers' existing relationships with mobile devices. First, we address the value propositions underpinning consumer involvement with mobile devices. Next, we canvass the types of involvement relevant to this consumption domain and argue that involvement, together with personal attributes innovativeness and self-efficacy, will influence use of m-services. Finally, implications for advertising delivered as an m-service are discussed, the potential for m-services advertising as part of m-commerce are canvassed, and directions for future research identified.

Finding order in chaos : a problem based collaborative assignment for 1300 students across 19 disciplines

The use of collaborative assignments for assessment is a risky undertaking for students and course designers. Yet the benefits, in terms of core learning outcomes, competencies, collaborative sense making and student involvement, suggest that the effort is worthwhile. Formal descriptions and rules do little to ameliorate the perception of risk and increased anxiety by students. (Ryan, 2007). BEB100 Introducing Professional Learning is a faculty-wide foundation unit with over 1300 students from 19 disciplines across the Faculty of the Built Environment and Engineering (“BEE”) at the Queensland University of Technology (“QUT”), Brisbane, Australia. Finding order in chaos outlines the approach and justification, assessment criteria, learning resources, teamwork tools, tutorial management, communication strategies, 2007-09 Student Learning Experience Survey results, annual improvements, findings and outcomes.

In search of a theory of integrated marketing communication

For the most part, the literature base for Integrated Marketing Communication (IMC) has developed from an applied or tactical level rather than from an intellectual or theoretical one. Since industry, practitioner and even academic studies have provided little insight into what IMC is and how it operates, our approach has been to investigate that other IMC community, that is, the academic or instructional group responsible for disseminating IMC knowledge. We proposed that the people providing course instruction and directing research activities have some basis for how they organize, consider and therefore instruct in the area of IMC. A syllabi analysis of 87 IMC units in six countries investigated the content of the unit, its delivery both physically and conceptually, and defined the audience of the unit. The study failed to discover any type of latent theoretical foundation that might be used as a base for understanding IMC. The students who are being prepared to extend, expand and enhance IMC concepts do not appear to be well-served by the curriculum we found in our research. The study concludes with a model for further IMC curriculum development.

A framework for analyzing system intelligence of the building control system : a study of the integrated building management system

The lack of satisfactory consensus for characterizing the system intelligence and structured analytical decision models has inhibited the developers and practitioners to understand and configure optimum intelligent building systems in a fully informed manner. So far, little research has been conducted in this aspect. This research is designed to identify the key intelligent indicators, and develop analytical models for computing the system intelligence score of smart building system in the intelligent building. The integrated building management system (IBMS) was used as an illustrative example to present a framework. The models presented in this study applied the system intelligence theory, and the conceptual analytical framework. A total of 16 key intelligent indicators were first identified from a general survey. Then, two multi-criteria decision making (MCDM) approaches, the analytic hierarchy process (AHP) and analytic network process (ANP), were employed to develop the system intelligence analytical models. Top intelligence indicators of IBMS include: self-diagnostic of operation deviations; adaptive limiting control algorithm; and, year-round time schedule performance. The developed conceptual framework was then transformed to the practical model. The effectiveness of the practical model was evaluated by means of expert validation. The main contribution of this research is to promote understanding of the intelligent indicators, and to set the foundation for a systemic framework that provide developers and building stakeholders a consolidated inclusive tool for the system intelligence evaluation of the proposed components design configurations.

Relationships between employees and their nomadic, non-territorial work environment

Recent and current socio-cultural trends are significant factors impacting on how business is conduced and correspondingly, on how work environments are designed. New communication technology is helping to break physical boundaries and change the way and speed of conducting business. One of the main characteristics of these new workplaces is non-permanency wherein the individual employee has no dedicated personally assigned office, work station, or desk. In this non-territorial, nomadic situation, employees undertake their work tasks in a wide variety of work settings inside and outside the office building. Such environments are understood to be must suitable where there is the need for high interaction with others as well as a high level of concentrated, independent work. This thesis reports on a project designed to develop a deeper understanding of the relationships between people (P) and their built environment (E) in the context of everyday work practice in a nomadic and non-territorial work environment. To achieve this, the study focuses on the experiences of employees as they understand them in relation to their work and the designed/ physical work environment. In this sense, the study is qualitative and grounded in nature. It does not assume any previously established theory nor test any presenting hypothesis. Instead it interviews the participants about their situations at work in their workplace, interprets natural interaction and creates a foundation for the development of theory informing workplace design, particularly theory that recognises the human nature of work and the need, as highlighted by several seminal researchers, for a greater understanding of how people manage and adapt in dynamic work environments.

The exploration of consumer power in online brand communities : a comparison case study in Australia and China

Aided by the development of information technology, the balance of power in the market place is rapidly shifting from marketers towards consumers and nowhere is this more obvious than in the online environment (Denegri-Knott, Zwick, & Schroeder, 2006; Moynagh & Worsley, 2002; Newcomer, 2000; Samli, 2001). From the inception and continuous development of the Internet, consumers are becoming more empowered. They can choose what they want to click on the Internet, they can shop and transact payments, watch and download video, chat with others, be it friends or even total strangers. Especially in online communities, like-minded consumers share and exchange information, ideas and opinions. One form of online community is the online brand community, which gathers specific brand lovers. As with any social unit, people form different roles in the community and exert different effects on each other. Their interaction online can greatly influence the brand and marketers. A comprehensive understanding of the operation of this special group form is essential to advancing marketing thought and practice (Kozinets, 1999). While online communities have strongly shifted the balance of power from marketers to consumers, the current marketing literature is sparse on power theory (Merlo, Whitwell, & Lukas, 2004). Some studies have been conducted from an economic point of view (Smith, 1987), however their application to marketing has been limited. Denegri-Knott (2006) explored power based on the struggle between consumers and marketers online and identified consumer power formats such as control over the relationship, information, aggregation and participation. Her study has built a foundation for future power studies in the online environment. This research project bridges the limited marketing literature on power theory with the growing recognition of online communities among marketing academics and practitioners. Specifically, this study extends and redefines consumer power by exploring the concept of power in online brand communities, in order to better understand power structure and distribution in this context. This research investigates the applicability of the factors of consumer power identified by Denegri-Knott (2006) to the online brand community. In addition, by acknowledging the model proposed by McAlexander, Schouten, & Koenig (2002), which emphasized that community study should focus on the role of consumers and identifying multiple relationships among the community, this research further explores how member role changes will affect power relationships as well as consumer likings of the brand. As a further extension to the literature, this study also considers cultural differences and their effect on community member roles and power structure. Based on the study of Hofstede (1980), Australia and China were chosen as two distinct samples to represent differences in two cultural dimensions, namely individualism verses collectivism and high power distance verses low power distance. This contribution to the research also helps answer the research gap identified by Muñiz Jr & O'Guinn (2001), who pointed out the lack of cross cultural studies within the online brand community context. This research adopts a case study methodology to investigate the issues identified above. Case study is an appropriate research strategy to answer “how” and “why” questions of a contemporary phenomenon in real-life context (Yin, 2003). The online brand communities of “Haloforum.net” in Australia and “NGA.cn” in China were selected as two cases. In-depth interviews were used as the primary data collection method. As a result of the geographical dispersion and the preference of a certain number of participants, online synchronic interviews via MSN messenger were utilized along with the face-to-face interviews. As a supplementary approach, online observation was carried over two months, covering a two week period prior to the interviews and a six week period following the interviews. Triangulation techniques were used to strengthen the credibility and validity of the research findings (Yin, 2003). The findings of this research study suggest a new definition of power in an online brand community. This research also redefines the consumer power types and broadens the brand community model developed by McAlexander et al. (2002) in an online context by extending the various relationships between brand and members. This presents a more complete picture of how the perceived power relationships are structured in the online brand community. A new member role is discovered in the Australian online brand community in addition to the four member roles identified by Kozinets (1999), in contrast however, all four roles do not exist in the Chinese online brand community. The research proposes a model which links the defined power types and identified member roles. Furthermore, given the results of the cross-cultural comparison between Australia and China showed certain discrepancies, the research suggests that power studies in the online brand community should be country-specific. This research contributes to the body of knowledge on online consumer power, by applying it to the context of an online brand community, as well as considering factors such as cross cultural difference. Importantly, it provides insights for marketing practitioners on how to best leverage consumer power to serve brand objective in online brand communities. This, in turn, should lead to more cost effective and successful communication strategies. Finally, the study proposes future research directions. The research should be extended to communities of different sizes, to different extents of marketer control over the community, to the connection between online and offline activities within the brand community, and (given the cross-cultural findings) to different countries. In addition, a greater amount of research in this area is recommended to determine the generalizability of this study.

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

Literature Review Value Alignment Process for Project Delivery

The objective of the project “Value Alignment Process for Project Delivery” is to provide a catalyst and tools for reform in the building and construction industry to transform business-as-usual performance into exceptional performance. The outcomes of this project will be beneficial to not only the construction industry, but to the community as a whole because a more sophisticated industry can deliver more effective use of assets, financing, operating and maintenance of facilities to suit the community’s needs. The research project consists of a study into best practice project delivery and the development of a suite of products, resources and services to guide project teams towards the best approach for a specific project. These resources will be focused on promoting the principles that underlie best practice project delivery, rather than on identifying a particular delivery system. The need for such tools and resources becomes more and more acute as the environment within which the construction industry operates becomes more and more complex, and as business and political imperatives shift to encompass or represent diverse stakeholder interests. To this end, this literature review looks at why it is essential to achieve transformation in the Australian construction industry in the context of its importance to the Australian economy. It seeks to investigate the concepts of ‘alignment’ and value’ as they pertain to construction industry processes and relationships. It comprehensively reviews drivers of project excellence and best practice project delivery principles and looks at how clients approach selection of project delivery systems. It critiques existing project delivery strategies and gives an overview of recent best practice initiatives. The literature review represents a milestone against the Project Agreement and forms a foundation document for this research project

Accounting : building business skills, 3rd ed.

The new edition of this widely used and respected introductory accounting textbook continues to provide students and academics with a well written and accessible resource, with ample illustrations and applications to business for a first study of accounting. The text effectively maintains the balance between a 'user' and 'preparer' perspective by integrating real financial information and business decisions throughout. Through the use of real company information and financial statements students will quickly appreciate the use and users of accounting information. The textbook clearly outlines to students how a financial statement - such as a balance sheet, income statement, cash flow statement - communicates the financing, operating, and investing activities of a business. The text builds a strong conceptual understanding and develops skills in the application of accounting principles and techniques, providing students with a solid foundation for further studies in accounting. The integral role of financial statements for decision making is also emphasised in this text and is reinforced throughout by the Decision Toolkit in each chapter. Students are provided with an extensive set of tools necessary to make business decisions based on financial information.

Building mentoring capacities in experienced teachers

While teacher education equips beginning teachers with critical knowledge and skills about teaching and fosters an understanding of learning in and from teaching some of the most critical elements of teaching are only learned in the workplace when beginning teachers commence their professional teaching careers. This transition to professional practice may be facilitated by mentoring from a more experienced teacher. Expert mentoring assists beginning teachers to build their teaching capacities more quickly and also lays the foundation for innovative professional practice. However, the presence of a mentor alone is not sufficient with the success of mentoring reliant on the skills and knowledge of mentors. Mentoring relationships are most effective when mentors are trained for their roles. While mentor preparation is the single most important factor in contributing to mentoring success, few teachers receive formal training to prepare them adequately for mentoring roles. The purpose of this paper is to report on the implementation of a mentoring development program designed to build mentoring capacities in experienced teachers. The program was trialled in a school in rural Australia. A range of qualitative data was collected from participants over the duration of the mentoring program and follow up data collected six months subsequent to the conclusion of the program.

Floating on a sea of talk: Reading comprehension through speaking and listening

Talk is the foundation for thought and understanding, and the key to literacy learning. Research demonstrates that powerful meta-cognitive strategies can be taught to help students self-monitor their comprehension when reading print and digital texts. This paper provides a repertoire of motivating speaking and listening tips to develop the meta-cognitive thinking of students in the elementary years.

Experimental methodology report

In architectural design and the construction industry, there is insufficient evidence about the way designers collaborate in their normal working environments using both traditional and digital media. It is this gap in empirical evidence that the CRC project, “Team Collaboration in High Bandwidth Virtual Environments” addresses. The project is primarily, but not exclusively, concerned with the conceptual stages of design carried out by professional designers working in different offices. The aim is to increase opportunities for communication and interaction between people in geographically distant locations in order to improve the quality of collaboration. In order to understand the practical implications of introducing new digital tools on working practices, research into how designers work collaboratively using both traditional and digital media is being undertaken. This will involve a series of empirical studies in the work places of the industry partners in the project. The studies of collaboration processes will provide empirical results that will lead to more effective use of virtual environments in design and construction processes. The report describes the research approach, the industry study, the methods for data collection and analysis and the foundation research methodologies. A distinctive aspect is that the research has been devised to enable field studies to be undertaken in a live industrial environment where the participant designers carry out real projects alongside their colleagues and in familiar locations. There are two basic research objectives: one is to obtain evidence about design practice that will inform the architecture and construction industries about the impact and potential benefit of using digital collaboration technologies; the second is to add to long term research knowledge of human cognitive and behavioural processes based on real world data. In order to achieve this, the research methods must be able to acquire a rich and heterogeneous set of data from design activities as they are carried out in the normal working environment. This places different demands upon the data collection and analysis methods to those of laboratory studies where controlled conditions are required. In order to address this, the research approach that has been adopted is ethnographic in nature and case study-based. The plan is to carry out a series of indepth studies in order to provide baseline results for future research across a wider community of user groups. An important objective has been to develop a methodology that will produce valid, significant and transferable results. The research will contribute to knowledge about how architectural design and the construction industry may benefit from the introduction of leading edge collaboration technologies. The outcomes will provide a sound foundation for the production of guidelines for the assessment of high bandwidth tools and their future deployment. The knowledge will form the basis for the specification of future collaboration products and collaboration processes. This project directly addresses the industry-identified focus on cultural change, image, e-project management, and innovative methods.

Financial accounting: building accounting knowledge

Financial Accounting: Building Accounting Knowledge is a new textbook written for the first financial accounting subject that a student majoring in accounting is required to study. Based on the successful introductory accounting textbook, 'Accounting: building business skills', this text will provide students and academics with a well written and accessible textbook on the principles of financial accounting, with ample illustrations and applications to business. The text maintains the balance between a 'user' and 'preparer' perspective effectively by integrating real financial information and business decision choices throughout the chapters. Through the use of real company information and financial statements students will quickly appreciate the use of accounting information. The textbook clearly outlines to students how accounting information communicates the financing, operating, and investing activities of a business. The text builds a strong conceptual understanding and develops skills in the application of accounting principles and techniques, providing students with a solid foundation for studying accounting.

Management

Building on the strengths of its popular previous editions, Management 4th Australasian edition has been thoroughly revised and updated to both reflect contemporarymanagement thinking and to highlight the issues facing managers of the21st century. A solid foundation of theory provides the background to a wealth ofillustrative examples, highlighting organisations operating inAustralia, New Zealand and the Asia-Pacific region. A balance of small-to medium- size enterprises and larger multinational corporations arefeatured. A critical thinking perspective is integrated throughout thebook, asking and encouraging student to analyse research and theory inthe light of contemporary management practice. Each copy of the printed textbook comes with a free copy of the Wiley Desktop Edition:a full electronic version of the text that allows students to easilysearch for key concepts, create their own colour-coded highlights andmake electronic notes in the text for revision. Key themes of the text include: The importance of ethical and socially responsible management Recognition of the continuing need to cater for the increasing diversity of the workforce The importance of managing people, technology, knowledge and quality in achieving organisational goals An appreciation of the challenges and opportunities presented bythe ever changing environment in which contemporary managers operate.