Evidence for three tumor suppressor loci on chromosome 9p involved in melanoma development

Cytogenetic and loss of heterozygosity (LOH) studies have long indicated the presence of a tumor suppressor gene (TSG) on 9p involved in the development of melanoma. Although LOH at 9p has been reported in approximately 60% of melanoma tumors, only 5-10% of these tumors have been shown to carry CDKN2A mutations, raising the possibility that another TSG involved in melanoma maps to chromosome 9p. To investigate this possibility, a panel of 37 melanomas derived from 35 individuals was analyzed for CDKN2A mutations by single-strand conformation polymorphism analysis and sequencing. The melanoma samples were then typed for 15 markers that map to 9p13-24 to investigate LOH trends in this region. In those tumors demonstrating retention of heterozygosity at markers flanking CDKN2A and LOH on one or both sides of the gene, multiplex microsatellite PCR was performed to rule out homozygous deletion of the region encompassing CDKN2A. CDKN2A mutations were found in tumors from 5 patients [5 (14%) of 35], 4 of which demonstrated LOH across the entire region examined. The remaining tumor with no observed LOH carried two point mutations, one on each allele. Although LOH was identified at one or more markers in 22 (59%) of 37 melanoma tumors corresponding to 20 (57%) of 35 individuals, only 11 tumors from 9 individuals [9 (26%) of 35] demonstrated LOH at D9S942 and D9S1748 the markers closest to CDKN2A. Of the remaining 11 tumors with LOH 9 demonstrated LOH at two or more contiguous markers either centromeric and/or telomeric to CDKN2A while retaining heterozygosity at several markers adjacent to CDKN2A. Multiplex PCR revealed one tumor carried a homozygous deletion extending from D9S1748 to the IFN-alpha locus. In the remaining eight tumors, multiplex PCR demonstrated that the observed heterozygosity was not attributable to homozygous deletion and stromal contamination at D9S1748, D9S942, or D9S974, as measured by comparative amplification strengths, which indicates that retention of heterozygosity with flanking LOH does not always indicate a homozygous deletion. This report supports the conclusions of previous studies that a least two TSGs involved in melanoma development in addition to CDKN2A may reside on chromosome 9p.

Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes

Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10−11, OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.

Public acceptance of carbon dioxide capture and storage in a proposed demonstration area

With the rising levels of CO2 in the atmosphere, low-emission technologies with carbon dioxide capture and storage (CCS) provide one option for transforming the global energy infrastructure into a more environmentally, climate sustainable system. However, like many technology innovations, there is a social risk to the acceptance of CCS. This article presents the findings of an engagement process using facilitated workshops conducted in two communities in rural Queensland, Australia, where a demonstration project for IGCC with CCS has been announced. The findings demonstrate that workshop participants were concerned about climate change and wanted leadership from government and industry to address the issue. After the workshops, participants reported increased knowledge and more positive attitudes towards CCS, expressing support for the demonstration project to continue in their local area. The process developed is one that could be utilized around the world to successfully engage communities on the low carbon emission technology options.

Value creation and value capture fro open source software publisher : a new business model based on mutualisation

Key topics: Since the birth of the Open Source movement in the mid-80's, open source software has become more and more widespread. Amongst others, the Linux operating system, the Apache web server and the Firefox internet explorer have taken substantial market shares to their proprietary competitors. Open source software is governed by particular types of licenses. As proprietary licenses only allow the software's use in exchange for a fee, open source licenses grant users more rights like the free use, free copy, free modification and free distribution of the software, as well as free access to the source code. This new phenomenon has raised many managerial questions: organizational issues related to the system of governance that underlie such open source communities (Raymond, 1999a; Lerner and Tirole, 2002; Lee and Cole 2003; Mockus et al. 2000; Tuomi, 2000; Demil and Lecocq, 2006; O'Mahony and Ferraro, 2007;Fleming and Waguespack, 2007), collaborative innovation issues (Von Hippel, 2003; Von Krogh et al., 2003; Von Hippel and Von Krogh, 2003; Dahlander, 2005; Osterloh, 2007; David, 2008), issues related to the nature as well as the motivations of developers (Lerner and Tirole, 2002; Hertel, 2003; Dahlander and McKelvey, 2005; Jeppesen and Frederiksen, 2006), public policy and innovation issues (Jullien and Zimmermann, 2005; Lee, 2006), technological competitions issues related to standard battles between proprietary and open source software (Bonaccorsi and Rossi, 2003; Bonaccorsi et al. 2004, Economides and Katsamakas, 2005; Chen, 2007), intellectual property rights and licensing issues (Laat 2005; Lerner and Tirole, 2005; Gambardella, 2006; Determann et al., 2007). A major unresolved issue concerns open source business models and revenue capture, given that open source licenses imply no fee for users. On this topic, articles show that a commercial activity based on open source software is possible, as they describe different possible ways of doing business around open source (Raymond, 1999; Dahlander, 2004; Daffara, 2007; Bonaccorsi and Merito, 2007). These studies usually look at open source-based companies. Open source-based companies encompass a wide range of firms with different categories of activities: providers of packaged open source solutions, IT Services&Software Engineering firms and open source software publishers. However, business models implications are different for each of these categories: providers of packaged solutions and IT Services&Software Engineering firms' activities are based on software developed outside their boundaries, whereas commercial software publishers sponsor the development of the open source software. This paper focuses on open source software publishers' business models as this issue is even more crucial for this category of firms which take the risk of investing in the development of the software. Literature at last identifies and depicts only two generic types of business models for open source software publishers: the business models of ''bundling'' (Pal and Madanmohan, 2002; Dahlander 2004) and the dual licensing business models (Välimäki, 2003; Comino and Manenti, 2007). Nevertheless, these business models are not applicable in all circumstances. Methodology: The objectives of this paper are: (1) to explore in which contexts the two generic business models described in literature can be implemented successfully and (2) to depict an additional business model for open source software publishers which can be used in a different context. To do so, this paper draws upon an explorative case study of IdealX, a French open source security software publisher. This case study consists in a series of 3 interviews conducted between February 2005 and April 2006 with the co-founder and the business manager. It aims at depicting the process of IdealX's search for the appropriate business model between its creation in 2000 and 2006. This software publisher has tried both generic types of open source software publishers' business models before designing its own. Consequently, through IdealX's trials and errors, I investigate the conditions under which such generic business models can be effective. Moreover, this study describes the business model finally designed and adopted by IdealX: an additional open source software publisher's business model based on the principle of ''mutualisation'', which is applicable in a different context. Results and implications: Finally, this article contributes to ongoing empirical work within entrepreneurship and strategic management on open source software publishers' business models: it provides the characteristics of three generic business models (the business model of bundling, the dual licensing business model and the business model of mutualisation) as well as conditions under which they can be successfully implemented (regarding the type of product developed and the competencies of the firm). This paper also goes further into the traditional concept of business model used by scholars in the open source related literature. In this article, a business model is not only considered as a way of generating incomes (''revenue model'' (Amit and Zott, 2001)), but rather as the necessary conjunction of value creation and value capture, according to the recent literature about business models (Amit and Zott, 2001; Chresbrough and Rosenblum, 2002; Teece, 2007). Consequently, this paper analyses the business models from these two components' point of view.

Using digital storytelling to capture responses to the Apology

This article discusses a pilot project that adapted the methods of digital storytelling and oral history to capture a range of personal responses to the official Apology to Australia’s Indigenous Peoples delivered by Prime Minister Kevin Rudd on 13 February 2008. The project was an initiative of State Library of Queensland and resulted in a small collection of multimedia stories, incorporating a variety of personal and political perspectives. The article describes how the traditional digital storytelling workshop method was adapted for use in the project, and then proceeds to reflect on the outcomes and continuing life of the project. The article concludes by suggesting that aspects of the resultant model might be applied to other projects carried out by cultural institutions and community-based media organizations.

Rare chromosome disorders and their developmental consequences

Professionals working in disability services often encounter clients who have chromosome disorders such as Williams, Angelman or Down syndromes. As chromosome testing becomes increasingly sophisticated, however, more people are being diagnosed with very rare chromosome disorders that are identified not by a syndrome name, but rather by a description of the number, size and shape of their chromosomes (called the karyotype) or by a report of chromosome losses and gains detected through an advanced process known as microarray-based comparative genomic hybridisation (array CGH). For practitioners who work with individuals with rare chromosome disorders and their families, a basic level of knowledge about the evolving field of genetics, as well as specific knowledge about chromosome abnormalities, is essential since they must be able to demonstrate their knowledge and skills to clients (Simic & Turk, 2004). In addition, knowledge about the developmental consequences of various rare chromosome disorders is important for guiding prognoses, expectations, decisions and interventions. The current article provides information that aims to help practitioners work more effectively with this population. It begins by presenting essential information about chromosomes and their numerical and structural abnormalities and then considers the developmental consequences of rare chromosome disorders through a critical review of relevant literature.

A brush with the real world : the future of inertial motion capture in live performance

3D Motion capture is a medium that plots motion, typically human motion, converting it into a form that can be represented digitally. It is a fast evolving field and recent inertial technology may provide new artistic possibilities for its use in live performance. Although not often used in this context, motion capture has a combination of attributes that can provide unique forms of collaboration with performance arts. The inertial motion capture suit used for this study has orientation sensors placed at strategic points on the body to map body motion. Its portability, real-time performance, ease of use, and its immunity from line-of-sight problems inherent in optical systems suggest it would work well as a live performance technology. Many animation techniques can be used in real-time. This research examines a broad cross-section of these techniques using four practice-led cases to assess the suitability of inertial motion capture to live performance. Although each case explores different visual possibilities, all make use of the performativity of the medium, using either an improvisational format or interactivity among stage, audience and screen that would be difficult to emulate any other way. A real-time environment is not capable of reproducing the depth and sophistication of animation people have come to expect through media. These environments take many hours to render. In time the combination of what can be produced in real-time and the tools available in a 3D environment will no doubt create their own tree of aesthetic directions in live performance. The case study looks at the potential of interactivity that this technology offers.

Inertial motion capture and live performance (with a focus on dance)

3D Motion capture is a fast evolving field and recent inertial technology may expand the artistic possibilities for its use in live performance. Inertial motion capture has three attributes that make it suitable for use with live performance; it is portable, easy to use and can operate in real-time. Using four projects, this paper discusses the suitability of inertial motion capture to live performance with a particular emphasis on dance. Dance is an artistic application of human movement and motion capture is the means to record human movement as digital data. As such, dance is clearly a field in which the use of real-time motion capture is likely to become more common, particularly as projected visual effects including real-time video are already often used in dance performances. Understandably, animation generated in real-time using motion capture is not as extensive or as clean as the highly mediated animation used in movies and games, but the quality is still impressive and the ‘liveness’ of the animation has compensating features that offer new ways of communicating with an audience.

The silk road project : dance and embodiment in the age of motion capture

The Silk Road Project was a practice-based research project investigating the potential of motion capture technology to inform perceptions of embodiment in dance performance. The project created a multi-disciplinary collaborative performance event using dance performance and real-time motion capture at Deakin University’s Deakin Motion Lab. Several new technological advances in producing real-time motion capture performance were produced, along with a performance event that examined the aesthetic interplay between a dancer’s movement and the precise mappings of its trajectories created by motion capture and real-time motion graphic visualisations.

Directing for the 360 degree frame : developing a directorial approach to performance capture

What happens when the traditional framing mechanisms of our performance environments are removed and we are forced as directors to work with actors in digital environments that capture performance in 360 degrees? As directors contend with the challenges of interactive performance, the emergence of the online audience and the powerful influence of the games industry, how can we approach the challenges of directing work that is performance captured and presented in real time using motion capture and associated 3D imaging software? The 360 degree real time capture of performance, while allowing for an unlimited amount of framing potential, demands a unique and uncompromisingly disciplined style of direction and performance that has thus far remained unstudied and unquantified. By a close analysis of the groundbreaking work of artists like Robert Zemeckis and the Wetta Digital studio it is possible to begin to quantify what the technical requirements and challenges of 360 degree direction might be, but little has been discovered about the challenges of communicating the unlimited potential of framing and focus to the actors who work with these directors within these systems. It cannot be argued that the potential of theatrical space has evolved beyond the physical and moved into a more accessible virtual and digitised form, so how then can we direct for this unlimited potential and where do we place the focus of our directed (and captured) performance?

A world elsewhere : virtual reality, motion capture and early modern theatre

This paper investigates virtual reality representations of the 1599 Boar’s Head Theatre and the Rose Theatre, two renaissance places and spaces. These models become a “world elsewhere” in that they represent virtual recreations of these venues in as much detail as possible. The models are based on accurate archeological and theatre historical records and are easy to navigate particularly for current use. This paper demonstrates the ways in which these models can be instructive for reading theatre today. More importantly we introduce human figures onto the stage via motion capture which allows us to explore the potential between space, actor and environment. This facilitates a new way of thinking about early modern playwrights’ “attitudes to locality and localities large and small”. These venues are thus activated to intersect productively with early modern studies so that the paper can test the historical and contemporary limits of such research.