Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds

Germline mutations within the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and one of its targets, the cyclin dependent kinase 4 (CDK4) gene, have been identified in a proportion of melanoma kindreds. In the case of CDK4, only one specific mutation, resulting in the substitution of a cysteine for an arginine at codon 24 (R24C), has been found to be associated with melanoma. We have previously reported the identification of germline CDKN2A mutations in 7/18 Australian melanoma kindreds and the absence of the R24C CDK4 mutation in 21 families lacking evidence of a CDKN2A mutation. The current study represents an expansion of these efforts and includes a total of 48 melanoma families from Australia. All of these families have now been screened for mutations within CDKN2A and CDK4, as well as for mutations within the CDKN2A homolog and 9p21 neighbor, the CDKN2B gene, and the alternative exon 1 (E1beta) of CDKN2A. Families lacking CDKN2A mutations, but positive for a polymorphism(s) within this gene, were further evaluated to determine if their disease was associated with transcriptional silencing of one CDKN2A allele. Overall, CDKN2A mutations were detected in 3/30 (10%) of the new kindreds. Two of these mutations have been observed previously: a 24 bp duplication at the 5' end of the gene and a G to C transversion in exon 2 resulting in an M531 substitution. A novel G to A transition in exon 2, resulting in a D108N substitution was also detected. Combined with our previous findings, we have now detected germline CDKN2A mutations in 10/48 (21%) of our melanoma kindreds. In none of the 'CDKN2A-negative' families was melanoma found to segregate with either an untranscribed CDKN2A allele, an R24C CDK4 mutation, a CDKN2B mutation, or an E1beta mutation. The last three observations suggest that these other cell cycle control genes (or alternative gene products) are either not involved at all, or to any great extent, in melanoma predisposition.

The Fifth 48 Hour Game Making Challenge (2011)

The 48-hour game making challenge started out in 2007 as a creative community event. We have run this event each year since and seen over 120 games made. 2011 was the most remarkable in that each of the 20 teams made a playable game – the shape of the challenge has changed …. We have invested in the process of reflective practice & action research, with the event being part of a sweep of programs that inform this research, with each year giving us fresh insights into both the creative practice and essential concerns, process and trends of the independent games industry creative community, which we then respond to within our curatorial development of the subsequent programming. The 2011 48-hour challenge research project focused on the people and the site. We were specifically interested in the manner in which the community occupied the creative space.

Perceived gender differences in STEM learning in the middle school

Women are underrepresented in science, technology, engineering and mathematics (STEM) university coursework, reflecting long-standing gender issues that have existed in core middle-school STEM subject areas. Using data from a survey and written responses, we report on findings following the introduction of engineering education in middle school classes across three schools (grade level 7, n=122). The engineering experiences fused science, technology and mathematics concepts. The survey revealed higher percentages for girls than boys in 13 of the 24 items; however there were six items with a 20% difference in their perceptions about learning in STEM. For instance, despite girls recording that they have been provided equal or more opportunities than boys in STEM, they believed they do not do as well as boys (80% boys, 48% girls) or want to seek a career in STEM (39% boys, 17% girls). The written responses revealed gender differences across a number of themes in the students’ responses, including resources, group work, the nature and type of learning experiences, content knowledge, and teachers’ instructional style. Exposing students to STEM education facilitates an awareness of their learning and may assist girls to consider studying STEM subjects or STEM careers.

Visualising the 48 hour game making challenge

We have always felt that “something very special” was happening in the 48hr and other similar game jams. This “something” is more than the intensity and challenge of the experience, although this certainly has appeal for the participants. We had an intuition that these intense 48 hour game jams exposed something pertinent to the changing shape of the Australian games industry where we see the demise of the late 20th century large studio - the “Night Elf” model and the growth of the small independent model. There are a large number of wider economic and cultural factors around this evolution but our interest is specifically in the change from “industry” to “creative industry” and the growth of games as a cultural media and art practice. If we are correct in our intuition, then illuminating this something also has important ramifications for those courses which teach game and interaction design and development. Rather than undertake a formal ethno-methodological approach, we decided to track as many of the actors in the event as possible. We documented the experience (Keith Novak’s beautiful B&W photography), the individual and their technology (IOGraph mouse tracking), the teams as a group (Time lapse photography) and movement tracking throughout the whole space (Blue tooth phone tracking). The raw data collected has given us opportunity to start a commentary on the “something special” happening in the 48hr.

Unusual scene detection using distributed behaviour model and sparse representation

The ability to detect unusual events in surviellance footage as they happen is a highly desireable feature for a surveillance system. However, this problem remains challenging in crowded scenes due to occlusions and the clustering of people. In this paper, we propose using the Distributed Behavior Model (DBM), which has been widely used in computer graphics, for video event detection. Our approach does not rely on object tracking, and is robust to camera movements. We use sparse coding for classification, and test our approach on various datasets. Our proposed approach outperforms a state-of-the-art work which uses the social force model and Latent Dirichlet Allocation.

Performance characteristics of compound curved sandwich shell structures

Sandwich shells have recently emerged as aesthetically pleasing, efficient and economical structural systems, with a number of applications. They combine the advantages of sandwich layer technology together with those of shell action. With different materials and thicknesses used in the sandwich layers, their performance characteristics largely remain un-quantified and there are no guidelines at present for their design. This research paper provides verification, through finite element modeling and testing, for the application of this technology to dome styled dwellings with research currently being conducted into the further application to roofing and floor structures.

Persistent digital hyperthermia over a 48 h period does not induce laminitis in horses

Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl 2 was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an internal control. Clinical signs of lameness at the walk were not detected at 0h, 24h or 48h post-infusion. Mean±SE hoof wall temperatures of the left forefoot (29.4±0.25°C) were higher (P<0.05) than those on the right (27.5±0.38°C). Serum insulin (15.0±2.89μIU/mL) and blood glucose (5.4±0.22mM) concentrations remained unchanged during the experiment. Histopathological evidence of laminitis was not detected in any horse. The results demonstrated that digital vasodilation up to 30 °C for a period of 48. h does not trigger laminitis in the absence of hyperinsulinaemia. Thus, although digital hyperthermia may play a role in the pathogenesis of laminitis, it is not the sole mechanism involved.

Assessment of tumor prevention in Type 1 Neurofibromatosis using a nitroxide compound

Background Type 1 Neurofibromatosis (NF1) is a genetic disorder linked to mutations of the NF1 gene. Clinical symptoms are varied, but hallmark features of the disease include skin pigmentation anomalies (café au lait macules, skinfold freckling) and dermal neurofibromas. Method These dermal manifestations of NF1 have previously been reported in a mouse model where Nf1+/− mice are topically treated with dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). We adopted this mouse model to test the protective effects of a nitroxide antioxidant, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO). Antioxidants have previously been shown to increase longevity in nf1-deficient fruitflies. Doses of 4 μM and 40 μM CTMIO provided ad libitum in drinking water were given to Nf1-deficient mice. Results Consistent with previous reports, Nf1-deficient mice showed a 4.7-fold increase in papilloma formation (P < 0.036). However, neither dose of CTMIO had any significant affect on papilloma formation. A non-significant decrease in skin pigmentation abnormalities was seen with 4 μM but not 40 μM CTMIO. Subsequent analysis of genomic DNA isolated from papillomas indicated that DMBA/TPA induced tumors did not exhibit a local loss of heterozygosity (LOH) at the Nf1 locus. Conclusion These data reveal that oral antioxidant therapy with CTMIO does not reduce tumor formation in a multistage cancer model, but also that this model does not feature LOH for Nf1.

Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine : involvement of adenosine and dopamine receptors

Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.

Evaluation of implementation of a healthy food and drink supply strategy throughout the whole school environment in Queensland state schools, Australia

BACKGROUND/OBJECTIVES: This paper reports on the evaluation of the Smart Choices healthy food and drink supply strategy for Queensland schools (Smart Choices) implementation across the whole school environment in state government primary and secondary schools in Queensland, Australia. SUBJECTS/METHODS: Three concurrent surveys using different methods for each group of stakeholders that targeted all 1275 school Principals, all 1258 Parent and Citizens’ Associations (P&Cs) and a random sample of 526 tuckshop convenors throughout Queensland. Nine hundred and seventy-three Principals, 598 P&Cs and 513 tuckshop convenors participated with response rates of 78%, 48% and 98%, respectively. RESULTS: Nearly all Principals (97%), P&Cs (99%) and tuckshop convenors (97%) reported that their school tuckshop had implemented Smart Choices. The majority of Principals and P&Cs reported implementation, respectively, in: school breakfast programs (98 and 92%); vending machine stock (94 and 83%); vending machine advertising (85 and 84%); school events (87 and 88%); school sporting events (81 and 80%); sponsorship and advertising (93 and 84%); fundraising events (80 and 84%); and sporting clubs (73 and 75%). Implementation in curriculum activities, classroom rewards and class parties was reported, respectively, by 97%, 86% and 75% of Principals. Respondents also reported very high levels of understanding of Smart Choices and engagement of the school community. CONCLUSIONS: The results demonstrated that food supply interventions to promote nutrition across all domains of the school environment can be implemented successfully.

Effect of a novel compound from Lycopodium obscurum L. on osteogenic activity of osteoblasts in vitro

We investigated the potential of an extract of Lycopodium obscurum L.; stigmastane-3-oxo-21-oic acid (SA), to enhance osteogensis of mouse osteoblastic MC3T3-E1 cells. SA at a concentration of 16 µM was found to have no significant effect upon the viability of the cells, thus concentrations of 8 µM and 16 µM of SA were used in all further experiments. Both concentrations of SA had an inhibitory affect upon alkaline phosphatase activity (ALP) after 8 days incubation, however, after 16 days activity was restored to control levels. However Alizarin red S staining showed increased levels of mineralization for both concentrations after 16 days culture. Real time PCR showed inhibition of genes Runx2 and Osterix genes responsible for the up-regulation of ALP. However early time point (8 days) up-regulation of bone matrix mineralization genes OPN and OCN, and late time point (16 days) up-regulation of both Jun-D and Fra-2 mRNA expression was significantly enhanced. These results suggest a potential me-chanism of SA in enhancing bone fracture healing is through the up-regulating bone matrix minera-lization.

Is mental health education really needed?

Dietitians play a key role in supporting and advocating for the physical health care of mental health (MH) consumers, with 68-80% seeing clients with associated depression issues in Australia. The DAA Mental Health Curricula Project found dietetic training in MH was inadequate and recommended increased MH education. A MH resource package was developed and sent to universities in 2010 for incorporation into teaching. The aim of this study was to assess dietetic students’ baseline MH knowledge, attitudes and exposure prior to dietetics coursework and package implementation. An online survey measured dietetic students’ mental health knowledge (MHK), attitudes towards mental illness (MHA) and previous exposure to mental illness. MHK was assessed by sixteen dietetics-specific questions. MHA were measured by Day’s Mental Illness Stigma Scale. Exposure was assessed using an adapted version of Eack’s Social Work Students’ Experiences with Schizophrenia questions. Fifty-nine dietetic students (30% response rate) from two universities were surveyed at the beginning of dietetic coursework. Survey responses revealed students had low MHK (mean 5.48, scale 0-16) with no significant difference between cohorts (p=0.67). Half of respondents (n=31) recorded never or rarely being in contact with people with mental illness. 82% of respondents (n=48) reported having no or little experience with mental illness. Data suggests low levels of sitgmatising attitudes about people with mental illness. Given the high prevalence of clients with MH issues in everyday dietetic practice, this study is a first step in addressing integration of MH education into dietetics training.

Average structure of an An (sub 48) plagioclase from the Hogarth Ranges

The average structure (CI) of a volcanic plagioclase megacryst with composition Ano, from the Hogarth Ranges, Australia, has been determined using three-dimensional, singlecrystal neutron and X-ray diffraction data. Least squaresr efinements, incorporating anisotropic thermal motion of all atoms and an extinction correction, resulted in weighted R factors (based on intensities) of 0.076 and 0.056, respectively, for the neutron and X-ray data. Very weak e reflections could be detected in long-exposure X-ray and electron diffraction photographs of this crystal, but the refined average structure is believed to be unaffected by the presence of such a weak superstructure. The ratio of the scattering power of Na to that of Ca is different for X ray and neutron radiation, and this radiation-dependence of scattering power has been used to determine the distribution of Na and Ca over a split-atom M site (two sites designated M' and M") in this Ano, plagioclase. Relative peak-height ratios M'/M", revealed in difference Fourier sections calculated from neutron and X-ray data, formed the basis for the cation-distribution analysis. As neutron and X-ray data sets were directly compared in this analysis, it was important that systematic bias between refined neutron and X-ray positional parameters could be demonstrated to be absent. In summary, with an M-site model constrained only by the electron-microprobedetermined bulk composition of the crystal, the following values were obtained for the M-site occupanciesN: ar, : 0.29(7),N ar. : 0.23(7),C ar, : 0.15(4),a nd Car" : 0.33(4). These results indicate that restrictive assumptions about M sites, on which previous plagioclase refinements have been based, are not applicable to this Ano, and possibly not to the entire compositional range. T-site ordering determined by (T-O) bond-length variation-t,o : 0.51(l), trm = t2o = t2m = 0.32(l)-is weak, as might be expectedf rom the volcanic origin of this megacryst.

Fresh water and acid sensitivity of authigenic clays in sandstone reservoirs

Authigenic illite-smectite and chlorite in reservoir sandstones from several Pacific rim sedimentary basins in Australia and New Zealand have been examined using an Electroscan Environmental Scanning Electron Microscope (ESEM) before, during, and after treatment with fresh water and HCl, respectively. These dynamic experiments are possible in the ESEM because, unlike conventional SEMs that require a high vacuum in the sample chamber (10-6 torr), the ESEM will operate at high pressures up to 20 torr. This means that materials and processes can be examined at high magnifications in their natural states, wet or dry, and over a range of temperatures (-20 to 1000 degrees C) and pressures. Sandstones containing the illite-smectite (60-70% illite interlayers) were flushed with fresh water for periods of up to 12 hours. Close examination of the same illite-smectite lines or filled pores, both before and after freshwater treatments, showed that the morphology of the illite-smectite was not changed by prolonged freshwater treatment. Chlorite-bearing sandstones (Fe-rich chlorite) were reacted with 1M to 10M HCl at temperatures of up to 80 degrees C and for periods of up to 48 hours. Before treatment the chlorites showed typically platy morphologies. After HCl treatment the chlorite grains were coated with an amorphous gel composed of Ca, Cl, and possibly amorphous Si, as determined by EDS analyses on the freshly treated rock surface. Brief washing in water removed this surface coating and revealed apparently unchanged chlorite showing no signs of dissolution or acid attack. However, although the chlorite showed no morphological changes, elemental analysis only detected silicon and oxygen.