Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk.

Genome-wide association studies (GWASs) have characterized 13 loci associated with melanoma, which only account for a small part of melanoma risk. To identify new genes with too small an effect to be detected individually but which collectively influence melanoma risk and/or show interactive effects, we used a two-step analysis strategy including pathway analysis of genome-wide SNP data, in a first step, and epistasis analysis within significant pathways, in a second step. Pathway analysis, using the gene-set enrichment analysis (GSEA) approach and the gene ontology (GO) database, was applied to the outcomes of MELARISK (3,976 subjects) and MDACC (2,827 subjects) GWASs. Cross-gene SNP-SNP interaction analysis within melanoma-associated GOs was performed using the INTERSNP software. Five GO categories were significantly enriched in genes associated with melanoma (false discovery rate ≤ 5% in both studies): response to light stimulus, regulation of mitotic cell cycle, induction of programmed cell death, cytokine activity and oxidative phosphorylation. Epistasis analysis, within each of the five significant GOs, showed significant evidence for interaction for one SNP pair at TERF1 and AFAP1L2 loci (pmeta-int  = 2.0 × 10(-7) , which met both the pathway and overall multiple-testing corrected thresholds that are equal to 9.8 × 10(-7) and 2.0 × 10(-7) , respectively) and suggestive evidence for another pair involving correlated SNPs at the same loci (pmeta-int  = 3.6 × 10(-6) ). This interaction has important biological relevance given the key role of TERF1 in telomere biology and the reported physical interaction between TERF1 and AFAP1L2 proteins. This finding brings a novel piece of evidence for the emerging role of telomere dysfunction into melanoma development.

Interactive Effects of Plant Species and Organic Carbon on Nitrate Removal in Chesapeake Bay Treatment Wetlands

Nitrate from agricultural runoff are a significant cause of algal blooms in estuarine ecosystems such as the Chesapeake Bay. These blooms block sunlight vital to submerged aquatic vegetation, leading to hypoxic areas. Natural and constructed wetlands have been shown to reduce the amount of nitrate flowing into adjacent bodies of water. We tested three wetland plant species native to Maryland, Typha latifolia (cattail), Panicum virgatum (switchgrass), and Schoenoplectus validus (soft-stem bulrush), in wetland microcosms to determine the effect of species combination and organic amendment on nitrate removal. In the first phase of our study, we found that microcosms containing sawdust exhibited significantly greater nitrate removal than microcosms amended with glucose or hay at a low nitrate loading rate. In the second phase of our study, we confirmed that combining these plants removed nitrate, although no one combination was significantly better. Furthermore, the above-ground biomass of microcosms containing switchgrass had a significantly greater percentage of carbon than microcosms without switchgrass, which can be studied for potential biofuel use. Based on our data, future environmental groups can make a more informed decision when choosing biofuel-capable plant species for artificial wetlands native to the Chesapeake Bay Watershed.

Adapting Behavioral Parent Training as an Interactive Computer Game

Behavioral Parent Training (BPT) is a well-established therapy that reduces child externalized behaviors and parent stress. Although BPT was originally developed for parents of children with defiant behaviors, the program’s key concepts are relevant to parenting all children. Since parents might not fully utilize BPT due to cost and program location, we created an online game as a low-cost, easily accessible alternative or complement to BPT. We tested the game with nineteen undergraduate students at the University of Maryland. The experimental group completed pretest survey on core BPT knowledge, played the game, and completed a BPT posttest, while the control group completed a pretest and posttest survey over a three week period. Participants in the experimental group also completed a survey to indicate their satisfaction with the overall program. The experimental group demonstrated significantly higher levels of BPT knowledge than the control group and high levels of satisfaction. This suggests that an interactive, online BPT platform is an engaging and accessible way for parents to learn key concepts.

The F4 fimbrial chaperone FaeE is stable as a monomer that does not require self-capping of its pilin-interactive surfaces.

Many Gram-negative bacteria use the chaperone-usher pathway to express adhesive surface structures, such as fimbriae, in order to mediate attachment to host cells. Periplasmic chaperones are required to shuttle fimbrial subunits or pilins through the periplasmic space in an assembly-competent form. The chaperones cap the hydrophobic surface of the pilins through a donor-strand complementation mechanism. FaeE is the periplasmic chaperone required for the assembly of the F4 fimbriae of enterotoxigenic Escherichia coli. The FaeE crystal structure shows a dimer formed by interaction between the pilin-binding interfaces of the two monomers. Dimerization and tetramerization have been observed previously in crystal structures of fimbrial chaperones and have been suggested to serve as a self-capping mechanism that protects the pilin-interactive surfaces in solution in the absence of the pilins. However, thermodynamic and biochemical data show that FaeE occurs as a stable monomer in solution. Other lines of evidence indicate that self-capping of the pilin-interactive interfaces is not a mechanism that is conservedly applied by all periplasmic chaperones, but is rather a case-specific solution to cap aggregation-prone surfaces.

The specification and design of an interactive virtual environment for use in teacher training

The original concept was to create a 'simulation' which would provide trainee teachers, specializing in Information and Communications Technology (ICT) with the opportunity to explore a primary school environment. Within the simulation, factors affecting the development and implementation of ICT would be modelled so that trainees would be able to develop the skills, knowledge and understanding necessary to identify appropriate strategies to overcome the limitations. To this end, we have developed Allsorts Primary - the prototype of a simulated interactive environment, representing a typical primary school

The Shared Memory Parallelisation of an Ocean Modelling Code using an Interactive Parallelisation Toolkit

This paper briefly describes an interactive parallelisation toolkit that can be used to generate parallel code suitable for either a distributed memory system (using message passing) or a shared memory system (using OpenMP). This study focuses on how the toolkit is used to parallelise a complex heterogeneous ocean modelling code within a few hours for use on a shared memory parallel system. The generated parallel code is essentially the serial code with OpenMP directives added to express the parallelism. The results show that substantial gains in performance can be achieved over the single thread version with very little effort.

Using an interactive parallelisation toolkit to parallelise an ocean modelling code

This paper describes an interactive parallelisation toolkit that can be used to generate parallel code suitable for either a distributed memory system (using message passing) or a shared memory system (using OpenMP). This study focuses on how the toolkit is used to parallelise a complex heterogeneous ocean modelling code within a few hours for use on a shared memory parallel system. The generated parallel code is essentially the serial code with OpenMP directives added to express the parallelism. The results show that substantial gains in performance can be achieved over the single thread version with very little effort.

Generating OpenMP code using an interactive parallelization environment

Code parallelization using OpenMP for shared memory systems is relatively easier than using message passing for distributed memory systems. Despite this, it is still a challenge to use OpenMP to parallelize application codes in a way that yields effective scalable performance when executed on a shared memory parallel system. We describe an environment that will assist the programmer in the various tasks of code parallelization and this is achieved in a greatly reduced time frame and level of skill required. The parallelization environment includes a number of tools that address the main tasks of parallelism detection, OpenMP source code generation, debugging and optimization. These tools include a high quality, fully interprocedural dependence analysis with user interaction capabilities to facilitate the generation of efficient parallel code, an automatic relative debugging tool to identify erroneous user decisions in that interaction and also performance profiling to identify bottlenecks. Finally, experiences of parallelizing some NASA application codes are presented to illustrate some of the benefits of using the evolving environment.

Using an interactive software environment for the parallelization of real-world scientific applications

The parallelization of real-world compute intensive Fortran application codes is generally not a trivial task. If the time to complete the parallelization is to be significantly reduced then an environment is needed that will assist the programmer in the various tasks of code parallelization. In this paper the authors present a code parallelization environment where a number of tools that address the main tasks such as code parallelization, debugging and optimization are available. The ParaWise and CAPO parallelization tools are discussed which enable the near automatic parallelization of real-world scientific application codes for shared and distributed memory-based parallel systems. As user involvement in the parallelization process can introduce errors, a relative debugging tool (P2d2) is also available and can be used to perform nearly automatic relative debugging of a program that has been parallelized using the tools. A high quality interprocedural dependence analysis as well as user-tool interaction are also highlighted and are vital to the generation of efficient parallel code and in the optimization of the backtracking and speculation process used in relative debugging. Results of benchmark and real-world application codes parallelized are presented and show the benefits of using the environment

Ghost/Machine: cinema in a digital age

Cinema, with its passive cinematic apparatus and linear narrative is often characterised as a contrast to new media narrative strategies, yet from Vertov’s Man with a Movie Camera to Mike Figgis’ TimeCode and Wong Kar Wei’s 2046 cinema provides narrative strategies and spatial conceptualisations which prefigure or are contiguous with new media environments. Both our perception of what cyberspace constitutes and the technology that actualises those perceptions arise out of and are driven by fantasy and desire. This paper will explore the metaphors used to represent and understand new media aesthetics through cinematic representations of new media environments. Two key themes relevant to new media aesthetics emerge. Irigaray, Haraway, and Grosz are used to explore the de-essentialising haptic and penetrative potential of new technologies and their ability to collapse the boundary between the body and the machine. The second fantasy, of new media as a liminal space that expresses the memorialising function of technology and its relation to mourning, is analysed using Benjamin, Burgin and Rutsky. These altered spaces and perceptions of the body and memory of the post-cinematic subject are illustrated through an analysis of Gondry’s Eternal Sunshine of the Spotless Mind and Jonze’s Being John Malkovich. [From the Author]

Representations of multicultural identities in British Cinema

This paper explores the transnational and interstitial dimensions of cultural production in Britain today, and the representation of migrant and diasporic identities in contemporary mainstream British cinema. The box office success of films like Gurindha Chadha’s Bhaji on the Beach (1993) and Bend it Like Beckham (2002) and East is East (Daniel O’Donnell 1999) and their precursors My Beautiful Launderette (Stephen Frears 1985), Sammy and Rosie Get Laid (Stephen Frears 1987) and the TV mini-series Buddha of Suburbia (Roger Mitchell 1993) seem to celebrate and articulate a set of values around hybridity and alterity: a discourse of multiculturalism. This paper will engage with a series of key questions. Are there ideological values implicit within and common to all these texts? Can we map a rhetoric or discourse of multiculturalism within popular culture? Do mainstream representations of immigrant identities represent a discourse of resistance, a decolonising global culture or is this Western brand of multiculturalism still located within an Orientalising gaze? In what ways are multiculturalism and postcolonialism overlapping and yet opposing rhetorics? [From the Author]