High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Pharmacogenetics of migraine : genetic variants and their potential role in migraine therapy

Migraine is a paroxysmal neurological disorder affecting up to 6% of males and 18% of females in the general population, and has been demonstrated to have a strong, but complex, genetic component. Genetic investigation of migraine provides hope that new targets for medications and individual specific therapy will be developed. The identification of polymorphisms or genetic biomarkers for disease susceptibility and treatment should aid in providing a better understanding of migraine pathology and, consequently, more appropriate and efficient treatment for migraineurs. In this review, we will discuss results investigating genetic biomarkers for migraine and their potential role in future therapy planning.

The influence of oxygenated organic aerosols (OOA) on the oxidative potential of diesel and biodiesel particulate matter

Generally, the magnitude of pollutant emissions from diesel engines running on biodiesel fuel is ultimately coupled to the structure of respective molecules that constitutes the fuel. Previous studies demonstrated the relationship between organic fraction of PM and its oxidative potential. Herein, emissions from a diesel engine running on different biofuels were analysed in more detail to explore the role different organic fractions play in the measured oxidative potential. In this work, a more detailed chemical analysis of biofuel PM was undertaken using a compact Time of Flight Aerosol Mass Spectrometer (c-ToF AMS). This enabled a better identification of the different organic fractions that contribute to the overall measured oxidative potentials. The concentration of reactive oxygen species (ROS) was measured using a profluorescent nitroxide molecular probe 9-(1,1,3,3-tetramethylisoindolin-2-yloxyl-5-ethynyl)-10-(phenylethynyl)anthracene (BPEAnit). Therefore the oxidative potential of the PM, measured through the ROS content, although proportional to the total organic content in certain cases shows a much higher correlation with the oxygenated organic fraction as measured by the c-ToF AMS. This highlights the importance of knowing the surface chemistry of particles for assessing their health impacts. It also sheds light onto new aspects of particulate emissions that should be taken into account when establishing relevant metrics for assessing health implications of replacing diesel with alternative fuels.

Capturing gazelles : features of high potential firms and new venture growth

This paper investigates the characteristics of ventures which have the potential to reach high growth and compares this with ‘everyday’ new ventures. Findings of interest in this paper include: • HP firms are characterised by higher human capital, are more likely to have a team of founders, are more likely to be product based. • HP firms are more likely to achieve more extreme levels of growth (both positive and negative). • HP ventures that make a loss are more likely to do so early in the venture process. Those that do hold on show that there can higher levels of loss made later on in firm development. HP firms have higher resource needs, in terms of seeking external finance, but are no more likely to receive external finance than regular firms.

The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

The intervening role of Agreeableness in the relationship between trait emotional intelligence and Machiavellianism : reassessing the potential dark side of EI

Previous research into the potential ‘dark’ side of trait emotional intelligence (EI) has repeatedly demonstrated that trait EI is negatively associated with Machiavellianism. In this study, we reassess the potential dark side of trait EI, by testing whether Agreeableness mediates and/or moderates the relationship between trait EI and Machiavellianism. Hypothesized mediation and moderation effects were tested using a large sample of 884 workers who completed several self-report questionnaires. Results provide support for both hypotheses; Agreeableness was found to mediate and moderate the relationship between trait EI and Machiavellianism. Overall, results indicate that individuals high in trait EI tend to have low levels of Machiavellianism because they generally have a positive nature (i.e. are agreeable) and not because they are emotionally competent per se. Results also indicate that individuals high in ‘perceived emotional competence’ have the potential to be high in Machiavellianism, particularly when they are low in Agreeableness.

Making the train : an examination of five perspectives of rail access and how they resonate with existing and potential passengers

Rail operators recognize a need to increase ridership in order to improve the economic viability of rail service, and to magnify the role that rail travel plays in making cities feel liveable. This study extends previous research that used cluster analysis with a small sample of rail passengers to identify five salient perspectives of rail access (Zuniga et al, 2013). In this project stage, we used correlation techniques to determine how those perspectives would resonate with two larger study populations, including a relatively homogeneous sample of university students in Brisbane, Australia and a diverse sample of rail passengers in Melbourne, Australia. Findings from Zuniga et al. (2013) described a complex typology of current passengers that was based on respondents’ subjective attitudes and perceptions rather than socio-demographic or travel behaviour characteristics commonly used for segmentation analysis. The typology included five qualitative perspectives of rail travel. Based on the transport accessibility literature, we expected to find that perspectives from that study emphasizing physical access to rail stations would be shared by current and potential rail passengers who live further from rail stations. Other perspectives might be shared among respondents who live nearby, since the relevance of distance would be diminished. The population living nearby would thus represent an important target group for increasing ridership, since making rail travel accessible to them does not require expansion of costly infrastructure such as new lines or stations. By measuring the prevalence of each perspective in a larger respondent pool, results from this study provide insight into the typical socio-demographic and travel behaviour characteristics that correspond to each perspective of intra-urban rail travel. In several instances, our quantitative findings reinforced Zuniga et al.’s (2013) qualitative descriptions of passenger types, further validating the original research. This work may directly inform rail operators’ approach to increasing ridership through marketing and improvements to service quality and station experience. Operators in other parts of Australia and internationally may also choose to replicate the study locally, to fine-tune understanding of diverse customer bases. Developing regional and international collaboration would provide additional opportunities to evaluate and benchmark service and station amenities as they address the various access dimensions.

An exploratory study of the potential of resurfacing articular cartilage with synthetic phospholipids

This thesis is aimed at further understanding the uppermost lipid-filled membranous layer (i.e. surface amorphous layer (SAL)) of articular cartilage and to develop a scientific framework for re-introducing lipids onto the surface of lipid-depleted articular cartilage (i.e. "resurfacing"). The outcome will potentially contribute to knowledge that will facilitate the repair of the articular surface of cartilage where degradation is limited to the loss of the lipids of the SAL only. The surface amorphous layer is of utmost importance to the effective load-spreading, lubrication, and semipermeability (which controls its fluid management, nutrient transport and waste removal) of articular cartilage in the mammalian joints. However, because this uppermost layer of cartilage is often in contact during physiological function, it is prone to wear and tear, and thus, is the site for damage initiation that can lead to the early stages of joint condition like osteoarthritis, and related conditions that cause pain and discomfort leading to low quality of life in patients. It is therefore imperative to conduct a study which offers insight into remedying this problem. It is hypothesized that restoration (resurfacing) of the surface amorphous layer can be achieved by re-introducing synthetic surface-active phospholipids (SAPL) into the joint space. This hypothesis was tested in this thesis by exposing cartilage samples whose surface lipids had been depleted to individual and mixtures of synthetic saturated and unsaturated phospholipids. The surfaces of normal, delipidized, and relipidized samples of cartilage were characterized for their structural integrity and functionality using atomic force microscope (AFM), confocal microscope (COFM), Raman spectroscopy, magnetic resonance imaging (MRI) with image processing in the MATLAB® environment and mechanical loading experiments. The results from AFM imaging, confocal microscopy, and Raman spectroscopy revealed a successful deposition of new surface layer on delipidized cartilage when incubated in synthetic phospholipids. The relipidization resulted in a significant improvement in the surface nanostructure of the artificially degraded cartilage, with the complete SAPL mixture providing better outcomes in comparison to those created with the single SAPL components (palmitoyl-oleoyl-phosphatidylcholine, POPC and dipalmitoyl-phosphatidylcholine, DPPC). MRI analysis revealed that the surface created with the complete mixture of synthetic lipids was capable of providing semipermeability to the surface layer of the treated cartilage samples relative to the normal intact surface. Furthermore, deformation energy analysis revealed that the treated samples were capable of delivering the elastic properties required for load bearing and recovery of the tissue relative to the normal intact samples, with this capability closer between the normal and the samples incubated in the complete lipid mixture. In conclusion, this thesis has established that it is possible to deposit/create a potentially viable layer on the surface of cartilage following degradation/lipid loss through incubation in synthetic lipid solutions. However, further studies will be required to advance the ideas developed in this thesis, for the development of synthetic lipid-based injections/drugs for treatment of osteoarthritis and other related joint conditions.

Zeta-potential and morphology of electrospun nano- and microfibers from biopolymers and their blends used as scaffolds in tissue engineering

Electrostatic spinning or electrospinning is a fiber spinning technique driven by a high-voltage electric field that produces fibers with diameters in a submicrometer to nanometer range.1 Nanofibers are typical one-dimensional colloidal objects with an increased tensile strength, whose length can achieve a few kilometers and the specific surface area can be 100 m2 g–1 or higher.2 Nano- and microfibers from biocompatible polymers and biopolymers have received much attention in medical applications3 including biomedical structural elements (scaffolding used in tissue engineering,2,4–6 wound dressing,7 artificial organs and vascular grafts8), drug and vaccine delivery,9–11 protective shields in speciality fabrics, multifunctional membranes, etc. Other applications concern superhydrophobic coatings,12 encapsulation of solid materials,13 filter media for submicron particles in separation industry, composite reinforcement and structures for nano-electronic machines.

Heat-producing crust regulation of subsurface temperatures : a stochastic model re-evaluation of the geothermal potential in western Queensland, Australia

A large subsurface, elevated temperature anomaly is well documented in Central Australia. High Heat Producing Granites (HHPGs) intersected by drilling at Innamincka are often assumed to be the dominant cause of the elevated subsurface temperatures, although their presence in other parts of the temperature anomaly has not been confirmed. Geological controls on the temperature anomaly remain poorly understood. Additionally, methods previously used to predict temperature at 5 km depth in this area are simplistic and possibly do not give an accurate representation of the true distribution and magnitude of the temperature anomaly. Here we re-evaluate the geological controls on geothermal potential in the Queensland part of the temperature anomaly using a stochastic thermal model. The results illustrate that the temperature distribution is most sensitive to the thermal conductivity structure of the top 5 km. Furthermore, the results indicate the presence of silicic crust enriched in heat producing elements between and 40 km.

From production to purpose : using design led innovation to Build Strategic Potential in a Family-Owned SME

There is an evident need to develop the strategic capabilities of companies from within, to ensure competitive competence in a time where strategy is a necessity. This paper is based on the first 4 months of a longitudinal embedded case study of a family-owned Australian small to medium enterprise, in their journey towards design integration. The first author was embedded as a ‘Design Innovation Catalyst’ to collaborate on overcoming early barriers of strategic development, using design led innovation. Action research methodology, semi-structured interviews with seven out of eight employees and a reflective journal revealed the absence of a shared vision, conflicting drivers and a focus on operational efficiency rather than strategy. Through the Catalyst’s facilitation, a company vision, general awareness, practice and knowledge in strategic development have emerged as the first steps to generating strategic design competence within the firm.

Synthesis and evaluation of resveratrol-based nitroxides as potential treatments for hypertension

The synthesis and evaluation of novel resveratrol-based nitroxides have been explored for the potential treatment of hypertension. New methodology for the direct aryl iodination of isoindoline and isoindoline nitroxide using periodic acid and potassium iodide in concentrated sulphuric acid was developed. Diiodinated tetramethyl and tetraethyl isoindolines and a tetramethyl isoindoline nitroxide were prepared in excellent yields (70 – 82%). A diiodinated tetraethyl isoindoline nitroxide was generated from the corresponding nitroxide in modest yield (37%) alongside iodinated nitrones. The mono-iodinated species were also generated in modest yields (34 – 48%). Incorporation of the nitroxide unit into the structure of resveratrol was achieved using palladium-catalysed Heck coupling. Use of the previously prepared iodo products 5-iodo-1,1,3,3-tetramethylisoindolin-2-yloyl 18 and 5,6-diiodo-1,1,3,3-tetramethylisoindolin-2-yloyl 22 gave resveratrol nitroxides 12 and 13 in yields of 50% (optimized) and 1.6% respectively. Preliminary evaluation of the resveratrol analogue 12 as a treatment for hypertension was undertaken in the DOCA-salt rat model. A reduction in systolic blood pressure as well as alleviation of ventricular hypertrophy was observed. A larger study involving the DOCA salt rats is currently in progress.

Safety at railway level crossings : driver acceptance of potential ITS interventions

There is a continuing need to improve safety at Railway Level Crossings (RLX) particularly those that do not have gates and lights regulating traffic flow. A number of Intelligent Transport System (ITS) interventions have been proposed to improve drivers’ awareness and reduce errors in detecting and responding appropriately at level crossings. However, as with other technologies, successful implementation and ultimately effectiveness rests with the acceptance of the technology by the end user. In the current research, four focus groups were held (n=38) with drivers in metropolitan and regional locations in Queensland to examine their perceptions of potential in-vehicle and road-based ITS interventions to improve safety at RLX. The findings imply that further development of the ITS interventions, in particular the design and related promotion of the final product, must consider ease of use, usefulness and relative cost.

The potential of Circles of Support and Accountability (COSA) to reduce child sexual abuse in Australia

This report addresses a number of issues relating to Circles of Support and Accountability, and their compatibility with the Australian criminal justice context, including: - What are Circles of Support and Accountability? - When and how did Circles of Support and Accountability emerge? - What forms do Circles of Support and Accountability take? - What is the purpose of Circles of Support and Accountability? - Where do Circles of Support and Accountability currently operate? - Why is it important for Australia to understand Circles of Support and Accountability? - What is the scope of the problem of child sexual abuse in Australia? - What is the research evidence about the effectiveness of Circles of Support and Accountability? - Some key issues for consideration. - Some limitations and potential “dangers” of Circles of Support and Accountability. - Recommendations for Australia. The report concludes that given the research evidence about Circles of Support and Accountability, Australia should build on its existing interest to more fully implement Circles of Support and Accountability, while taking the limitations of this criminal justice measure into consideration.

Potential role of bcl-2 as a suppressor of tumour angiogenesis in non- small-cell lung cancer

It has been reported that genes regulating apoptosis may play a role in tumoral angiogenesis. This study examined the relationship between tumour vascularization, a measure of tumour angiogenesis, and bcl-2 and p53 expression in operable non-small-cell lung cancer (NSCLC). The relationship between bcl-2, p53 and tumour vascularization and epidermal-growth-factor- receptor(EGFR) and c-erbB-2 expression was also studied. Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl-2, p53, EGFR and c-erbB-2 expression. bcl-2 expression was found in 20/107 (19%) cases and was associated with squamous-cell histology (p = 0.03). A strong inverse relationship was found between bcl-2 expression and vascular grade (p = 0.005). All c-erbB-2-positive cases were negative for bcl-2 expression (p = 0.01). Overall no association was found between c-erbB-2 expression and vascular grade. However, in bcl-2-negative cases positive c-erbB-2 expression correlated with low angiogenesis (p = 0.05). No relationship was found between p53 and EGFR expression and bcl-2, c-erbB-2 or vascular grade. The improved prognosis reported in bcl-2-positive NSCLC may be related to low tumour vascularization. The results suggest that the anti-apoptotic gene bcl- 2 plays a role in regulating tumour angiogenesis. Since normal lung epithelium expresses bcl-2, a sequence of tumour progression involving loss of bcl-2, then activation of c-erbB-2 or increase in tumour vascularization is proposed.