SNP technologies for drug discovery : a current review

Single nucleotide polymorphisms (SNPs) are unique genetic differences between individuals that contribute in significant ways to the determination of human variation including physical characteristics like height and appearance as well as less obvious traits such as personality, behaviour and disease susceptibility. SNPs can also significantly influence responses to pharmacotherapy and whether drugs will produce adverse reactions. The development of new drugs can be made far cheaper and more rapid by selecting participants in drug trials based on their genetically determined response to drugs. Technology that can rapidly and inexpensively genotype thousands of samples for thousands of SNPs at a time is therefore in high demand. With the completion of the human genome project, about 12 million true SNPs have been identified to date. However, most have not yet been associated with disease susceptibility or drug response. Testing for the appropriate drug response SNPs in a patient requiring treatment would enable individualised therapy with the right drug and dose administered correctly the first time. Many pharmaceutical companies are also interested in identifying SNPs associated with polygenic traits so novel therapeutic targets can be discovered. This review focuses on technologies that can be used for genotyping known SNPs as well as for the discovery of novel SNPs associated with drug response.

A longitudinal study comparing bereavement phenomena in recently bereaved spouses, adult children and parents

Objective: The study investigated previous research findings and clinical impressions which indicated that the intensity of grief for parents who had lost a child was likely to be higher than that for widows/widowers, who in turn were likely to have more intense reactions than adult children losing a parent. Method: In order to compare the intensities of the bereavement reactions among representative community samples of bereaved spouses (n = 44), adult children (n = 40) and parents (n = 36), and to follow the course of such phenomena, a detailed Bereavement Questionnaire was administered at four time points over a 13-month period following the loss. Results: Measures based on items central to the construct of bereavement showed significant time and group differences in accordance with the proposed hypothesis. More global items associated with the construct of resolution showed a significant time effect, but without significant group differences. Conclusions: Evidence from this study supports the hypothesis that in non-clinical, community-based populations the frequency with which core bereavement phenomena are experienced is in the order: bereaved parents bereaved spouses bereaved adult children.

The role of periosteum : a neglected aspect of osteoporosis

Most current studies on the pathogenesis of osteoporosis emphasize the bone metabolic activities occurring on endosteal surfaces, whereas the periosteal aspect is somewhat neglected. In terms of bone physiology, periosteum plays a determining role in de novo cortical bone formation and cortical bone expansion through periosteum is the most efficient way of increasing bone strength against fractures. Despite the important role of periosteum in the pathogenesis and treatment of osteoporosis, little is known about the structural and cellular features of periosteum in osteoporosis. This chapter will focus on the major changes occurring in the periosteum of osteoporosis and possible implications of these changes in the pathogenesis of osteoporosis. The changes identified in the periosteum of osteoporosis are mainly located in the metaphyseal compartment, which include: (a) much thicker and more cellular cambial layer; (b) increased number of TRAP (tartrate resistant acid phosphatase), VEGF (vascular endothelial growth factor) cells and the degree of vascularization; and (c) enhanced expression of sympathetic nerve fibers. The structural and cellular changes of osteoporotic periosteum indicate that periosteum plays an important role in the cortical bone resorption in metaphyseal areas and this pathological process may be regulated by the sympathetic nervous system.

The true cost and performance of individual residential property investment and the implication on real estate agency practice

Investment in residential property in Australia is not dominated by the major investment institutions in to the same degree as the commercial, industrial and retail property markets. As at December 2001, the Property Council of Australia Investment Performance Index contained residential property with a total value of $235 million, which represents only 0.3% of the total PCA Performance Index value. The majority of investment in the Australian residential property market is by small investment companies and individual investors. The limited exposure of residential property in the institutional investment portfolios has also limited the research that has been undertaken in relation to residential property performance. However the importance of individual investment in residential property is continuing to gain importance as both individuals are now taking control of their own superannuation portfolios and the various State Governments of Australia are decreasing their involvement in the construction of public housing by subsidizing low-income families into the private residential property market. This paper will: • Provide a comparison of the cost to initially purchase residential property in the various capital city residential property markets in Australia, and • Analyse the true cost and investment performance of residential property in the main residential property markets in Australia based on a standard investment portfolio in each of the State capital cities and relate these results to real estate marketing and agency practice.

Particle emissions, volatility, and toxicity from an ethanol fumigated compression ignition engine

Particle emissions, volatility, and the concentration of reactive oxygen species (ROS) were investigated for a pre-Euro I compression ignition engine to study the potential health impacts of employing ethanol fumigation technology. Engine testing was performed in two separate experimental campaigns with most testing performed at intermediate speed with four different load settings and various ethanol substitutions. A scanning mobility particle sizer (SMPS) was used to determine particle size distributions, a volatilization tandem differential mobility analyzer (V-TDMA) was used to explore particle volatility, and a new profluorescent nitroxide probe, BPEAnit, was used to investigate the potential toxicity of particles. The greatest particulate mass reduction was achieved with ethanol fumigation at full load, which contributed to the formation of a nucleation mode. Ethanol fumigation increased the volatility of particles by coating the particles with organic material or by making extra organic material available as an external mixture. In addition, the particle-related ROS concentrations increased with ethanol fumigation and were associated with the formation of a nucleation mode. The smaller particles, the increased volatility, and the increase in potential particle toxicity with ethanol fumigation may provide a substantial barrier for the uptake of fumigation technology using ethanol as a supplementary fuel.

Osteoarthritic cartilage chondrocytes alter subchondral bone osteoblast differentiation via MAPK signalling pathway involving ERK1/2

Osteoarthritic subchondral bone is characterized by abnormal bone density and enhanced production of bone turnover markers, an indication of osteoblast dysfunction. Several studies have proposed that pathological changes in articular cartilage influence the subchondral bone changes, which are typical of the progression of osteoarthritis; however, direct evidence of this has yet to be reported. The aim of the present study was to investigate what effects articular cartilage cells, isolated from normal and osteoarthritic joints, may have on the subchondral bone osteoblast phenotype, and also the potential involvement of the mitogen activated protein kinase (MAPK) signalling pathway during this process. Our results suggest that chondrocytes isolated from a normal joint inhibited osteoblast differentiation, whereas chondrocytes isolated from an osteoarthritic joint enhanced osteoblast differentiation, both via a direct and indirect cell interaction mechanisms. Furthermore, the interaction of subchondral bone osteoblasts with osteoarthritic chondrocyte conditioned media appeared to significantly activate ERK1/2 phosphorylation. On the other hand, conditioned media from normal articular chondrocytes did not affect ERK1/2 phosphorylation. Inhibition of the MAPK–ERK1/2 pathways reversed the phenotype changes of subchondral bone osteoblast, which would otherwise be induced by the conditioned media from osteoarthritic chondrocytes. In conclusion, our findings provide evidence that osteoarthritic chondrocytes affect subchondral bone osteoblast metabolism via an ERK1/2 dependent pathway.

Unwrapping an ancient Egyptian mummy using x-rays

This article describes a project to unwrap an ancient Egyptian mummy using X-ray computed tomography (CT). About 600 X-ray CT images were obtained through the mummified body of a female named Tjetmutjengebtiu (or Jeni for short), who was a singer in the great temple of Karnak in Egypt during the 22nd dynasty (c. 945-715 BC). The X-ray CT images reveal details of the remains of body organs, wrappings and jewellery. 3D reconstructions of Jeni’s teeth suggest that she was probably only around 20 years old when she died, although the cause of death cannot be ascertained from the CT scans. The CT images were used to build a 3D model of Jeni’s head which enabled an artist to paint a picture of what Jeni may have looked like during life. A PowerPoint presentation and movie clips are provided as supplementary material that may be useful for teaching.

Conceptualising a Chinese corporate governance framework : tensions between tradition, ideologies and modernity

Reflects on the challenges facing China's efforts to reform its corporate governance framework, and the extent to which the modernisation can be reconciled with the country's cultural traditions. Examines the development of China's legal and economic reforms since 1978, the debate which these have generated ad the shortcomings of the current corporate governance regime. Discusses how Confucian principles might be applied to issues of director's duties and corporate governance, and explains the benefits of such an approach.

Application of autologous periosteal cells for the regeneration of class III furcation defects in Beagle dogs

The aim of this study was to evaluate the healing of class III furcation defects following transplantation of autogenous periosteal cells combined with b-tricalcium phosphate (b-TCP). Periosteal cells obtained from Beagle dogs’ periosteum explant cultures, were inoculated onto the surface of b-TCP. Class III furcation defects were created in the mandibular premolars. Three experimental groups were used to test the defects’ healing: group A, b-TCP seeded with periosteal cells were transplanted into the defects; group B, b-TCP alone was used for defect filling; and group C, the defect was without filling materials. Twelve weeks post surgery, the tissue samples were collected for histology, immunohistology and X-ray examination. It was found that both the length of newly formed periodontal ligament and the area of newly formed alveolar bone in group A, were significantly increased compared with both group B and C. Furthermore, both the proportion of newly formed periodontal ligament and newly formed alveolar bone in group A were much higher than those of group B and C. The quantity of cementum and its percentage in the defects (group A) were also significantly higher than those of group C. These results indicate that autogenous periosteal cells combined with b-TCP application can improve periodontal tissue regeneration in class III furcation defects.

The importance of environmental issues and costs in Life Cycle Cost Analysis (LCCA) for highway projects

Sustainability has been increasingly recognised as an integral part of highway infrastructure development. In practice however, the fact that financial return is still a project’s top priority for many, environmental aspects tend to be overlooked or considered as a burden, as they add to project costs. Sustainability and its implications have a far-reaching effect on each project over time. Therefore, with highway infrastructure’s long-term life span and huge capital demand, the consideration of environmental cost/ benefit issues is more crucial in life-cycle cost analysis (LCCA). To date, there is little in existing literature studies on viable estimation methods for environmental costs. This situation presents the potential for focused studies on environmental costs and issues in the context of life-cycle cost analysis. This paper discusses a research project which aims to integrate the environmental cost elements and issues into a conceptual framework for life cycle costing analysis for highway projects. Cost elements and issues concerning the environment were first identified through literature. Through questionnaires, these environmental cost elements will be validated by practitioners before their consolidation into the extension of existing and worked models of life-cycle costing analysis (LCCA). A holistic decision support framework is being developed to assist highway infrastructure stakeholders to evaluate their investment decision. This will generate financial returns while maximising environmental benefits and sustainability outcome.

Employers and child workers : an institutional approach

This article explores employers' perspectives on the introduction of child employment legislation in Australia through the lens of the three pillars—regulative, normative and cultural-cognitive—of institutional theory. The study extends the traditional industrial relations (IR) focus on regulation to examine how human resource (HR) practices around child employment become legitimised, normalised and socially supported.

Profiling off-road motorcycle and all-terrain riders in Queensland, Australia

The current research aimed to profile off-road riders to identify specific sub-groups in relation to their risk-related behaviours and perceptions. A total of 235 adults from the Australian state of Queensland who had ridden a motorcycle or ATV off-road in the last 12 months were recruited. A cluster analysis was applied to the survey data. Two distinct clusters of riders were identified, which corresponded with the self-report of injury from an off-road riding crash in the prior 12 months. The injured cluster had a significantly higher mean risk propensity and use of safety equipment, though did not differ on self-reported risk taking. The injured cluster as a whole included a higher percentage of males, was younger, and rode more often for recreational or competitive purposes than the non-crash involved cluster. The results indicate that the crash cluster may be both more aware of the potential risks of riding and more willing to ride in a riskier manner.