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.

Teacher-child relationship quality for young children with parent reported language concerns

Previous research has demonstrated the importance of the qualities of the teacher-child relationship on children’s development. Close teacher-child relationships are especially important for children at risk. Positive relationships have been shown to have beneficial effects on children’s social and academic development (Birch & Ladd, 1997; Pianta & Stuhlman, 2004). Children with language difficulties are likely to face increased risks with regard to long term social and academic outcomes. The purpose of the current research was to gain greater understanding of the qualities of teacher-child relationships for young children with parent reported language concerns. The research analyses completed for this thesis involved the use of data from the public-access database of Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC). LSAC is a longitudinal study involving a nationally representative sample of 10,000 Australian children. Data are being collected biennially from 2004 (Wave 1 data collection) until 2010 (Wave 4 data collection). LSAC has a cross-sequential research design involving two cohorts, an infant cohort (0-1 year at age of recruitment) and a kindergarten cohort (4-5 years at age of recruitment). Two studies are reported in this thesis using data for the LSAC Kindergarten Cohort which had 4983 child participants at recruitment. Study 1 used Wave 1 data to identify the differences between teacher-child relationship qualities for children with parent reported language concerns and their peers. Children identified by parents for whom concerns were held about their receptive and expressive language, as measured by items from the Parents’ Evaluation of Developmental Status (PEDS) (Glascoe, 2000) were the target (at risk) group in the study (n = 210). A matched case control group of peers (n = 210), matched on the child characteristics of sex, age, cultural and linguistic differences (CALD), and socio-economic positioning (SEP), were the comparison group for this analysis. Teacher-child relationship quality was measured by teacher reports on the Closeness and Conflict scales from the short version of the Student-Teacher Relationship Scale (STRS) (Pianta, 2001). There were statistically significant differences in the levels of closeness and conflict between the two groups. The target group had relationships with their teachers that had lower levels of closeness and higher levels of conflict than the control group. Study 2 reports analyses that examined the stability of the qualities of the teacher-child relationships at Wave 1 (4-5 years) and the qualities of the teacher-child relationships at Wave 2 (6-7 years). This time frame crosses the period of the children’s transition to school. The study examined whether early patterns in the qualities of the teacher-child relationship for children with parent reported language concerns at Wave 1 predicted the qualities of the teacher-child relationship outcomes in the early years of formal school. The sample for this study consisted of the group of children identified with PEDS language concerns at Wave 1 who also had teacher report data at Wave 2 (n = 145). Teacher-child relationship quality at Wave 1 and Wave 2 was again measured by the STRS scales of Closeness and Conflict. Results from multiple regression models indicated that teacher-child relationship quality at Wave 1 significantly contributed to the prediction of the quality of the teacher-child relationship at Wave 2, beyond other predictor variables included in the regression models. Specifically, Wave 1 STRS Closeness scores were the most significant predictor for STRS Closeness scores at Wave 2, while Wave 1 STRS Conflict scores were the only significant predictor for Wave 2 STRS Conflict outcomes. These results indicate that the qualities of the teacher-child relationship experienced prior to school by children with parent reported language concerns remained stable across transitions into formal schooling at which time the child had a different teacher. The results of these studies provide valuable insight into the nature of teacher-child relationship quality for young children with parent reported language concerns. These children experienced teacher-child relationships of a lower quality when compared with peers and, additionally, the qualities of these relationships prior to formal schooling were predictive of the qualities of the relationships in the early years of formal schooling. This raises concerns, given the increased risks of poorer social and academic outcomes already faced by children with language difficulties, that these early teacher-child relationships have an impact on future teacher-child relationships. Results of these studies are discussed with these considerations in mind and also discussed in terms of the implications for educational theory, policy and practice.

Hypercapitalism: language, new media and social perceptions of value

Using examples from contemporary policy and business discourses, and exemplary historical texts dealing with the notion of value, I put forward an argument as to why a critical scholarship that draws on media history, language analysis, philosophy and political economy is necessary to understand the dynamics of what is being called 'the global knowledge economy'. I argue that the social changes associated with new modes of value determination are closely associated with new media forms.

Peer to peer English/Chinese cross-language information retrieval

Peer to peer systems have been widely used in the internet. However, most of the peer to peer information systems are still missing some of the important features, for example cross-language IR (Information Retrieval) and collection selection / fusion features. Cross-language IR is the state-of-art research area in IR research community. It has not been used in any real world IR systems yet. Cross-language IR has the ability to issue a query in one language and receive documents in other languages. In typical peer to peer environment, users are from multiple countries. Their collections are definitely in multiple languages. Cross-language IR can help users to find documents more easily. E.g. many Chinese researchers will search research papers in both Chinese and English. With Cross-language IR, they can do one query in Chinese and get documents in two languages. The Out Of Vocabulary (OOV) problem is one of the key research areas in crosslanguage information retrieval. In recent years, web mining was shown to be one of the effective approaches to solving this problem. However, how to extract Multiword Lexical Units (MLUs) from the web content and how to select the correct translations from the extracted candidate MLUs are still two difficult problems in web mining based automated translation approaches. Discovering resource descriptions and merging results obtained from remote search engines are two key issues in distributed information retrieval studies. In uncooperative environments, query-based sampling and normalized-score based merging strategies are well-known approaches to solve such problems. However, such approaches only consider the content of the remote database but do not consider the retrieval performance of the remote search engine. This thesis presents research on building a peer to peer IR system with crosslanguage IR and advance collection profiling technique for fusion features. Particularly, this thesis first presents a new Chinese term measurement and new Chinese MLU extraction process that works well on small corpora. An approach to selection of MLUs in a more accurate manner is also presented. After that, this thesis proposes a collection profiling strategy which can discover not only collection content but also retrieval performance of the remote search engine. Based on collection profiling, a web-based query classification method and two collection fusion approaches are developed and presented in this thesis. Our experiments show that the proposed strategies are effective in merging results in uncooperative peer to peer environments. Here, an uncooperative environment is defined as each peer in the system is autonomous. Peer like to share documents but they do not share collection statistics. This environment is a typical peer to peer IR environment. Finally, all those approaches are grouped together to build up a secure peer to peer multilingual IR system that cooperates through X.509 and email system.

Does venture opportunity variation matter? investigating systematic process differences between innovative and imitative new ventures

The central thesis in the article is that the venture creation process is different for innovative versus imitative ventures. This holds up; the pace of the process differs by type of venture as do, in line with theory-based hypotheses, the effects of certain human capital (HC) and social capital (SC) predictors. Importantly, and somewhat unexpectedly, the theoretically derived models using HC, SC, and certain controls are relatively successful explaining progress in the creation process for the minority of innovative ventures, but achieve very limited success for the imitative majority. This may be due to a rationalistic bias in conventional theorizing and suggests that there is need for considerable theoretical development regarding the important phenomenon of new venture creation processes. Another important result is that the building up of instrumental social capital, which we assess comprehensively and as a time variant construct, is important for making progress with both types of ventures, and increasingly, so as the process progresses. This result corroborates with stronger operationalization and more appropriate analysis method what previously published research has only been able to hint at.

Space-time variation of malaria incidence in Yunnan province, China

Abstract Background Understanding spatio-temporal variation in malaria incidence provides a basis for effective disease control planning and monitoring. Methods Monthly surveillance data between 1991 and 2006 for Plasmodium vivax and Plasmodium falciparum malaria across 128 counties were assembled for Yunnan, a province of China with one of the highest burdens of malaria. County-level Bayesian Poisson regression models of incidence were constructed, with effects for rainfall, maximum temperature and temporal trend. The model also allowed for spatial variation in county-level incidence and temporal trend, and dependence between incidence in June–September and the preceding January–February. Results Models revealed strong associations between malaria incidence and both rainfall and maximum temperature. There was a significant association between incidence in June–September and the preceding January–February. Raw standardised morbidity ratios showed a high incidence in some counties bordering Myanmar, Laos and Vietnam, and counties in the Red River valley. Clusters of counties in south-western and northern Yunnan were identified that had high incidence not explained by climate. The overall trend in incidence decreased, but there was significant variation between counties. Conclusion Dependence between incidence in summer and the preceding January–February suggests a role of intrinsic host-pathogen dynamics. Incidence during the summer peak might be predictable based on incidence in January–February, facilitating malaria control planning, scaled months in advance to the magnitude of the summer malaria burden. Heterogeneities in county-level temporal trends suggest that reductions in the burden of malaria have been unevenly distributed throughout the province.

Learning, language and leadership : conduits to dynamic public service networks

Networks are having a profound impact on the way society is organised at the local, national and international level. Networks are not ‘business as usual’. The defining feature of networks and a key indicator for their success is the strength and quality of the interactions between members. This relational power of networks provides the mechanism to bring together previously dispersed and even competitive entities into a collective venture. Such an operating context demands the ability to work in a more horizontal, relational manner. In addition a social infrastructure must be formed that will support and encourage efforts to become more collaborative. This paper seeks to understand how network members come to know about working in networks, how they work on their relationships and create new meanings about the nature of their linked work. In doing so, it proposes that learning, language and leadership, herein defined as the ‘3Ls’ represent critical mediating aspects for networks.

Final : report assessing risk and variation in maintenance and rehabilitation costs for road network

This report presents the results of research projects conducted by The Australian Cooperative Research Centre for Construction Innovation, Queensland University of Technology, RMIT University, Queensland Government Department of Main Roads and Queensland Department of Public Works. The research projects aimed at developing a methodology for assessing variation and risk in investment in road network, including the application of the method in assessing road network performance and maintenance and rehabilitation costs for short- and long-term future investment.

Report : development of a methodology for assessing variation in maintenance and rehabilitation costs

In the previous research CRC CI 2001-010-C “Investment Decision Framework for Infrastructure Asset Management”, a method for assessing variation in cost estimates for road maintenance and rehabilitation was developed. The variability of pavement strength collected from a 92km national highway was used in the analysis to demonstrate the concept. Further analysis was conducted to identify critical input parameters that significantly affect the prediction of road deterioration. In addition to pavement strength, rut depth, annual traffic loading and initial roughness were found to be critical input parameters for road deterioration. This report presents a method developed to incorporate other critical parameters in the analysis, such as unit costs, which are suspected to contribute to a certain degree to cost estimate variation. Thus, the variability of unit costs will be incorporated in this analysis. Bruce Highway located in the tropical east coast of Queensland has been identified to be the network for the analysis. This report presents a step by step methodology for assessing variation in road maintenance and rehabilitation cost estimates.

Literacy, numeracy and learning in school-aged children identified as having speech and language impairment in early childhood

The progress of a nationally representative sample of 3632 children was followed from early childhood through to primary school, using data from the Longitudinal Study of Australian Children (LSAC). The aim was to examine the predictive effects of different aspects of communicative ability, and of early vs. sustained identification of speech and language impairment, on children's achievement and adjustment at school. Four indicators identified speech and language impairment: parent-rated expressive language concern; parent-rated receptive language concern; use of speech-language pathology services; below average scores on the adapted Peabody Picture Vocabulary Test-III. School outcomes were assessed by teachers' ratings of language/literacy ability, numeracy/mathematical thinking and approaches to learning. Comparison of group differences, using ANOVA, provided clear evidence that children who were identified as having speech and language impairment in their early childhood years did not perform as well at school, two years later, as their non-impaired peers on all three outcomes: Language and Literacy, Mathematical Thinking, and Approaches to Learning. The effects of early speech and language status on literacy, numeracy, and approaches to learning outcomes were similar in magnitude to the effect of family socio-economic factors, after controlling for child characteristics. Additionally, early identification of speech and language impairment (at age 4-5) was found to be a better predictor of school outcomes than sustained identification (at aged 4-5 and 6-7 years). Parent-reports of speech and language impairment in early childhood are useful in foreshadowing later difficulties with school and providing early intervention and targeted support from speech-language pathologists and specialist teachers.

Case study of collaborative learning in two contexts : what do English language learners gain?

This chapter describes the use of collaborative learning as an approach to enhance English language learning by students from non-English speaking backgrounds. Communicative Language Teaching (CLT) principles were applied to two case studies, one comprising of undergraduate English as Foreign Language Learners in Turkey and the other involved English as Second Language learners in Australia. Social constructivism inspired communicative language teaching using collaborative learning activities such as team work, interactive peer-based learning, and iterative stages of learning matrix were incorporated to enhance students' learning outcomes. Data collected after the CLT intervention was made up of field notes, reflective logs and focus group interviews which revealed complementarities, as well as subtle differences between the two cases. The findings were summarized as learning dispositions; speaking fluency and confidence; learning diagnostics and completion deficiencies; task engagement, flow theory and higher order thinking skills; in addition to self efficacy and development of student identity. CLT has the potential to provide a more inclusive and dynamic education for diverse learners through vital outcomes and benefits which resonate with the real world.

Language and Inclusion in Mainstream Classrooms

Understanding what the teacher says or what is written in texts used in class is a key to academic engagement. Yet, for students who are learning the medium of instruction as an additional language, understanding is often elusive. The study reported in this chapter looked at how African middle school students and parents, and educators in Australian schools, talked about problems of understanding, and responsibility for redressing these, at intensive language school and in transition to a mainstream Australian high school. In general, participants assumed students should signal confusion and teachers should resolve it. However, student talk of current and past anxiety about asking for help in class warrants attention. Challenges include: (1) the need to create receptive peer environments for asking questions; and (2) to recognise when it is inappropriate to rely on students signalling confusion.

Critical literacy and second language learning

An introductory overview of the historical foundations, practical precedents of current 'critical' approaches to English as a Second Language teaching - with specific reference to 'critical pedagogy' and 'text analytic' work.

Justifications in young children’s language in an early childhood classroom

This paper examines the interactional phenomenon of justification as it is produced in young children’s language. A justification provides a reason for one’s position and can be produced in children’s language at an early age. There are various pragmatic reasons for justifications. For example, justifications may be drawn upon by members to compensate for the disruption of the existing social order or to explain something that is possibly questionable. Justifications are also drawn upon to extend or close disputes. This study uses the analytical techniques of conversation analysis and membership categorisation to analyse video-recorded and transcribed interactions of young children (aged 4-6 years) in a preparatory classroom in a primary school in Australia. The focus is an episode that occurred within the block play area of the classroom that involved a dispute of ownership relating to a small, wooden plank. In analysing this dispute, justifications were frequent occurrences and the young participants drew upon justificatory devices in their everyday arguments. As the turns surrounding the justificatory language were examined, a pattern emerged: in each excerpt observed, a justification arose in response to a challenge. This pattern provided the basis for developing a model that helped to discern where, why and what type of justifications occurred in the interaction. To depict this interactional phenomenon, the model of ‘if x, then y’ was used, ‘x’ referring to the challenge or prompt, and ‘y’ referring to the justificatory response. Justifications related to the concepts of ownership and were used as devices by those engaged in disputes to support their positions and provide reasons for their actions. The children drew upon these child-constructed rules as resources to use in disputes with their peers, in order to construct and maintain the social order of the block area in the classroom.