914 resultados para Single Point Mutations
Resumo:
Traditional information retrieval (IR) systems respond to user queries with ranked lists of relevant documents. The separation of content and structure in XML documents allows individual XML elements to be selected in isolation. Thus, users expect XML-IR systems to return highly relevant results that are more precise than entire documents. In this paper we describe the implementation of a search engine for XML document collections. The system is keyword based and is built upon an XML inverted file system. We describe the approach that was adopted to meet the requirements of Content Only (CO) and Vague Content and Structure (VCAS) queries in INEX 2004.
Resumo:
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.
Resumo:
This is an initial report of the PolyU SD part of the team to study Pre-fabricated Building Design and Construction Methodology and marks the completion of Phase 1. It follows our first notes prepared for the meeting on 2 February that identified some critical issues including future lifestyles, life expectancy of buildings, sustainability, size, flexibility and planning considerations. It is also an expansion of our presentation in Dongguan on 23 February. It is not a comprehensive survey of existing approaches or possible ways forward, but it has homed in on certain specific issues and does give specific examples to make the suggestions concrete. It is recommended that more comprehensive research be done to establish previous work and experience internationally. It is also recommended that more research be done on lifestyles as a preliminary to developing at least three concepts for evaluation before proceeding to the detailed design of one concept for full prototyping and market testing. The goal at this point is not to define a single direction but to suggest several future trajectories for further consideration. By the same token, this report is not intended as an exhaustive description of the considerable base of knowledge and ideas brought by the PolyU team to this exciting task. Before taking on an issue of this magnitude and importance in the definition of Hong Kong's future, one must carry out a thoughtful analysis of the issues at hand and an informed definition of paradigms, directions, goals and methods whereby our energies can be best used in the next steps. This report is the result of this analysis
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Cultural policy settings attempting to foster the growth and development of the Australian feature film industry in era of globalisation are coming under increasing pressure. Global forces and emerging production and distribution models are challenging the “narrowness” of cultural policy – mandating a particular film culture, circumscribing certain notions of value and limiting the variety of films produced through cultural policy driven subvention models. Australian horror film production is an important case study. Horror films are a production strategy well suited to the financial limitations of the Australian film industry with competitive advantages for producers against international competitors. However, emerging within a “national” cinema driven by public subsidy and social/cultural objectives, horror films – internationally oriented with a low-culture status – have been severely marginalised within public funding environments. This paper introduces Australian horror film production, and examines the limitations of cultural policy, and the impacts of these questions for the Producer Offset.
Resumo:
Debates concerning the veracity, ethics and politics of the documentary form circle endlessly around the function of those who participate in it, and the meaning attributed to their participation. Great significance is attached to the way that documentary filmmakers do or do not participate in the world they seek to represent, just as great significance is attached to those subjects whose participation extends beyond playing the part of eyewitness or expert, such that they become part of the very filmmaking process itself. This Ph.D. explores the interface between documentary practice and participatory culture by looking at how their practices, discursive fields and histories intersect, but also by looking at how participating in one might mean participating in the other. In short, the research is an examination of participatory culture through the lens of documentary practice and documentary criticism. In the process, however, this examination of participatory culture will in turn shed light on documentary thinking, especially the meaning and function of ‘the participant’ in contemporary documentary practice. A number of ways of conceiving of participation in documentary practice are discussed in this research, but one of the ideas that gives purpose to that investigation is the notion that the participant in contemporary documentary practice is someone who belongs to a participatory culture in particular. Not only does this mean that those subjects who play a part in a documentary are already informed by their engagement with a range of everyday media practices before the documentary apparatus arrives, the audience for such films are similarly informed and engaged. This audience have their own expectations about how they should be addressed by media producers in general, a fact that feeds back into their expectations about participatory approaches to documentary practice too. It is the ambition of this research to get closer to understanding the relationship between participants in the audience, in documentary and ancillary media texts, as well as behind the camera, and to think about how these relationships constitute a context for the production and reception of documentary films, but also how this context might provide a model for thinking about participatory culture itself. One way that documentary practice and participatory culture converge in this research is in the kind of participatory documentary that I call the ‘Camera Movie’, a narrow mode of documentary filmmaking that appeals directly to contemporary audiences’ desires for innovation and participation, something that is achieved in this case by giving documentary subjects control of the camera. If there is a certain inevitability about this research having to contend with the notion of the ‘participatory documentary’, the ‘participatory camera’ also emerges strongly in this context, especially as a conduit between producer and consumer. Making up the creative component of this research are two documentaries about the reality television event Band In A Bubble, and participatory media practices more broadly. The single-screen film, Hubbub , gives form to the collective intelligence and polyphonous voice of contemporary audiences who must be addressed and solicited in increasingly innovative ways. One More Like That is a split-screen, DVD-Video with alternate audio channels selected by a user who thereby chooses who listens and who speaks in the ongoing conversation between media producers and media consumers. It should be clear from the description above that my own practice does not extend to highly interactive, multi-authored or web-enabled practices, nor the distributed practices one might associate with social media and online collaboration. Mine is fundamentally a single authored, documentary video practice that seeks to analyse and represent participatory culture on screen, and for this reason the Ph.D. refrains from a sustained discussion of the kinds of collaborative practices listed above. This is not to say that such practices don’t also represent an important intersection of documentary practice and participatory culture, they simply represent a different point of intersection. Being practice-led, this research takes its procedural cues from the nature of the practice itself, and sketches parameters that are most enabling of the idea that the practice sets the terms of its own investigation.