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.

Persistence of multiple genetic lineages within intra-host populations of Ross River virus

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances

A tissue engineering solution for segmental defect regeneration in load-bearing long bones

The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep - a model closely resembling human bone formation and structure - were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

Bone tissue engineering : reconstruction of critical sized segmental bone defects in the ovine tibia

Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds. Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.

Development and characterisation of tri- and tetra-nucleotide polymorphic microsatellite markers for skipjack tuna (Katsuwonus pelamis)

Skipjack tuna (katsuwonus pelamis) (SJT) is the largest tuna fishery in all the major oceans around the world, and the largest marine fishery in Sri Lanka. Knowledge of genetic population structure and effective population size of SJT in the Indian Ocean and other major oceans, however, is still lacking for better management practices and conservation strategies. We developed microsatellite genetic markers using SJT around Sri Lanka in the Indian Ocean, and characterise one tri- and seven tetra-nucleotide microsatellite loci isolated from enriched genomic libraries from SJT, to provide tools for addressing both conservation and fisheries management questions. An analysis of these eight microsatellite markers in two populations of SJT from eastern Sri Lanka (n = 44) and the Maldives Islands (n = 53) showed that all eight microsatellites were polymorphic with an average number of alleles per locus of 11.80 (range 5-27). Expected heterozygosities at marker loci ranged from 0.450 to 0.961. These markers are being used currently to characterise population structure and extent of natural gene flow in SJT populations from the eastern and western Indian Ocean. No significant linkage disequilibrium was detected among any loci pairs.

Multi-objective design optimization of morphing UAV aerofoil/wing using hybridised MOGA

The paper investigates two advanced Computational Intelligence Systems (CIS) for a morphing Unmanned Aerial Vehicle (UAV) aerofoil/wing shape design optimisation. The first CIS uses Genetic Algorithm (GA) and the second CIS uses Hybridized GA (HGA) with the concept of Nash-Equilibrium to speed up the optimisation process. During the optimisation, Nash-Game will act as a pre-conditioner. Both CISs; GA and HGA, are based on Pareto optimality and they are coupled to Euler based Computational Fluid Dynamic (CFD) analyser and one type of Computer Aided Design (CAD) system during the optimisation.

Innovative damage assessment of steel truss bridges using modal strain energy correlation

As a part of vital infrastructure and transportation network, bridge structures must function safely at all times. Bridges are designed to have a long life span. At any point in time, however, some bridges are aged. The ageing of bridge structures, given the rapidly growing demand of heavy and fast inter-city passages and continuous increase of freight transportation, would require diligence on bridge owners to ensure that the infrastructure is healthy at reasonable cost. In recent decades, a new technique, structural health monitoring (SHM), has emerged to meet this challenge. In this new engineering discipline, structural modal identification and damage detection have formed a vital component. Witnessed by an increasing number of publications is that the change in vibration characteristics is widely and deeply investigated to assess structural damage. Although a number of publications have addressed the feasibility of various methods through experimental verifications, few of them have focused on steel truss bridges. Finding a feasible vibration-based damage indicator for steel truss bridges and solving the difficulties in practical modal identification to support damage detection motivated this research project. This research was to derive an innovative method to assess structural damage in steel truss bridges. First, it proposed a new damage indicator that relies on optimising the correlation between theoretical and measured modal strain energy. The optimisation is powered by a newly proposed multilayer genetic algorithm. In addition, a selection criterion for damage-sensitive modes has been studied to achieve more efficient and accurate damage detection results. Second, in order to support the proposed damage indicator, the research studied the applications of two state-of-the-art modal identification techniques by considering some practical difficulties: the limited instrumentation, the influence of environmental noise, the difficulties in finite element model updating, and the data selection problem in the output-only modal identification methods. The numerical (by a planer truss model) and experimental (by a laboratory through truss bridge) verifications have proved the effectiveness and feasibility of the proposed damage detection scheme. The modal strain energy-based indicator was found to be sensitive to the damage in steel truss bridges with incomplete measurement. It has shown the damage indicator's potential in practical applications of steel truss bridges. Lastly, the achievement and limitation of this study, and lessons learnt from the modal analysis have been summarised.

Application of a human bone engineering platform to an in vitro and in vivo breast cancer metastasis model

Breast cancer in its advanced stage has a high predilection to the skeleton. Currently, treatment options of breast cancer-related bone metastasis are restricted to only palliative therapeutic modalities. This is due to the fact that mechanisms regarding the breast cancer celI-bone colonisation as well as the interactions of breast cancer cells with the bone microenvironment are not fully understood, yet. This might be explained through a lack of appropriate in vitro and in vivo models that are currently addressing the above mentioned issue. Hence the hypothesis that the translation of a bone tissue engineering platform could lead to improved and more physiological in vitro and in vivo model systems in order to investigate breast cancer related bone colonisation was embraced in this PhD thesis. Therefore the first objective was to develop an in vitro model system that mimics human mineralised bone matrix to the highest possible extent to examine the specific biological question, how the human bone matrix influences breast cancer cell behaviour. Thus, primary human osteoblasts were isolated from human bone and cultured under osteogenic conditions. Upon ammonium hydroxide treatment, a cell-free intact mineralised human bone matrix was left behind. Analyses revealed a similar protein and mineral composition of the decellularised osteoblast matrix to human bone. Seeding of a panel of breast cancer cells onto the bone mimicking matrix as well as reference substrates like standard tissue culture plastic and collagen coated tissue culture plastic revealed substrate specific differences of cellular behaviour. Analyses of attachment, alignment, migration, proliferation, invasion, as well as downstream signalling pathways showed that these cellular properties were influenced through the osteoblast matrix. The second objective of this PhD project was the development of a human ectopic bone model in NOD/SCID mice using medical grade polycaprolactone tricalcium phosphate (mPCL-TCP) scaffold. Human osteoblasts and mesenchymal stem cells were seeded onto an mPCL-TCP scaffold, fabricated using a fused deposition modelling technique. After subcutaneous implantation in conjunction with the bone morphogenetic protein 7, limited bone formation was observed due to the mechanical properties of the applied scaffold and restricted integration into the soft tissue of flank of NOD/SCID mice. Thus, a different scaffold fabrication technique was chosen using the same polymer. Electrospun tubular scaffolds were seeded with human osteoblasts, as they showed previously the highest amount of bone formation and implanted into the flanks of NOD/SCID mice. Ectopic bone formation with sufficient vascularisation could be observed. After implantation of breast cancer cells using a polyethylene glycol hydrogel in close proximity to the newly formed bone, macroscopic communication between the newly formed bone and the tumour could be observed. Taken together, this PhD project showed that bone tissue engineering platforms could be used to develop an in vitro and in vivo model system to study cancer cell colonisation in the bone microenvironment.

Piecing together an integrative taxonomic puzzle: microsatellite, wing shape and aedeagus length analyses of Bactrocera dorsalis s.l. (Diptera: Tephritidae) find no evidence of multiple lineages in a proposed contact zone along the Thai/Malay Peninsula

Bactrocera dorsalis (Hendel) and B. papayae Drew & Hancock represent a closely related sibling species pair for which the biological species limits are unclear; i.e., it is uncertain if they are truely two biological species, or one biological species which has been incorrectly taxonomically split. The geographic ranges of the two taxa are thought to abut or overlap on or around the Isthmus of Kra, a recognised biogeographic barrier located on the narrowest portion of the Thai Peninsula. We collected fresh material of B. dorsalis sensu lato (i.e., B. dorsalis sensu stricto + B. papayae) in a north-south transect down the Thai Peninsula, from areas regarded as being exclusively B. dorsalis s.s., across the Kra Isthmus, and into regions regarded as exclusively B. papayae. We carried out microsatellite analyses and took measurements of male genitalia and wing shape. Both the latter morphological tests have been used previously to separate these two taxa. No significant population structuring was found in the microsatellite analysis and results were consistent with an interpretation of one, predominantly panmictic population. Both morphological datasets showed consistent, clinal variation along the transect, with no evidence for disjunction. No evidence in any tests supported historical vicariance driven by the Isthmus of Kra, and none of the three datasets supported the current taxonomy of two species. Rather, within and across the area of range overlap or abutment between the two species, only continuous morphological and genetic variation was recorded. Recognition that morphological traits previously used to separate these taxa are continuous, and that there is no genetic evidence for population segregation in the region of suspected species overlap, is consistent with a growing body of literature that reports no evidence of biological differentiation between these taxa.

Innovative approaches to teaching engineering drawing at tertiary institutions

This paper arises from our concern for the level of teaching of engineering drawing at tertiary institutions in Australia. Little attention is paid to teaching hand drawing and tolerancing. Teaching of engineering drawing is usually limited to computer-aided design (CAD) using AutoCAD or one of the solid-modelling packages. As a result, many engineering graduates have diffi culties in understanding how views are produced in different projection angles, are unable to produce engineering drawings of professional quality, or read engineering drawings, and unable to select fits and limits or surface roughness. In the Faculty of Built Environment and Engineering at the Queensland University of Technology new approaches to teaching engineering drawing have been introduced. In this paper the results of these innovative approaches are examined through surveys and other research methods.

Minimization of railhead edge stresses through shape optimization

The railhead is severely stressed under the localized wheel contact patch close to the gaps in insulated rail joints. A modified railhead profile in the vicinity of the gapped joint, through a shape optimization model based on a coupled genetic algorithm and finite element method, effectively alters the contact zone and reduces the railhead edge stress concentration significantly. Two optimization methods, a grid search method and a genetic algorithm, were employed for this optimization problem. The optimal results from these two methods are discussed and, in particular, their suitability for the rail end stress minimization problem is studied. Through several numerical examples, the optimal profile is shown to be unaffected by either the magnitude or the contact position of the loaded wheel. The numerical results are validated through a large-scale experimental study.

Collaborative efforts to enhance power engineering education in Australia

A review of the issues for supporting learning of power engineering in Australia is presented in this paper. The learning needs of students and the support available in blended learning and through distance educations are explored in this review. Specific software tools to assist the learning environment are appraised and the relevance for the next generation of power engineers assessed.

β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice

Objective The spondylarthritides (SpA), including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of the large peripheral and axial joints, eyes, skin, ileum, and colon. Genetic studies reveal common candidate genes for AS, PsA, and Crohn's disease, including IL23R, IL12B, STAT3, and CARD9, all of which are associated with interleukin-23 (IL-23) signaling downstream of the dectin 1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17–dependent inflammatory arthritis developed after dectin 1–mediated fungal infection. This study was undertaken to determine whether SKG mice injected with 1,3-β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process. Methods SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly, and organs were assessed for pathologic features. Anti–IL-23 monoclonal antibodies were injected into curdlan-treated SKG mice. CD4+ T cells were transferred from curdlan-treated mice to SCID mice, and sera were analyzed for autoantibodies. Results After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle, and sacroiliac joint arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell– and IL-23–dependent and were transferable to SCID recipients with CD4+ T cells. SpA was associated with collagen- and proteoglycan-specific autoantibodies. Conclusion Our findings indicate that the SKG ZAP-70W163C mutation predisposes BALB/c mice to SpA, resulting from innate and adaptive autoimmunity, after systemic β-glucan or mannan exposure.