Proteasome inhibitors as anti-cancer agents

The ubiquitin (Ub)-proteasome pathway is the major nonlysosomal pathway of proteolysis in human cells and accounts for the degradation of most short-lived, misfolded or damaged proteins. This pathway is important in the regulation of a number of key biological regulatory mechanisms. Proteins are usually targeted for proteasome-mediated degradation by polyubiquitinylation, the covalent addition of multiple units of the 76 amino acid protein Ub, which are ligated to 1-amino groups of lysine residues in the substrate. Polyubiquitinylated proteins are degraded by the 26S proteasome, a large, ATP-dependent multicatalytic protease complex, which also regenerates monomeric Ub. The targets of this pathway include key regulators of cell proliferation and cell death. An alternative form of the proteasome, termed the immunoproteasome, also has important functions in the generation of peptides for presentation by MHC class I molecules. In recent years there has been a great deal of interest in the possibility that proteasome inhibitors, through elevation of the levels of proteasome targets, might prove useful as a novel class of anti-cancer drugs. Here we review the progress made to date in this area and highlight the potential advantages and weaknesses of this approach.

Undrained sediment loading key to long-runout submarine mass movements : evidence from the Caribbean Volcanic Arc

Long undersea debris runout can be facilitated by a boundary layer formed by weak marine sediments under a moving slide mass. Undrained loading of such offshore sediment results in a profound drop of basal shear resistance, compared to subaerial shear resistance, enabling long undersea runout. Thus large long-runout submarine landslides are not truly enigmatic (Voight and Elsworth 1992, 1997), but are understandable in terms of conventional geotechnical principles. A corollary is that remoulded undrained strength, and not friction angle, should be used for basal resistance in numerical simulations. This hypothesis is testable via drilling and examining the structure at the soles of undersea debris avalanches for indications of incorporation of sheared marine sediments, by tests of soil properties, and by simulations. Such considerations of emplacement process are an aim of ongoing research in the Lesser Antilles (Caribbean Sea), where multiple offshore debris avalanche and dome-collapse debris deposits have been identified since 1999 on swath bathymetric surveys collected in five oceanographic cruises. This paper reviews the prehistoric and historic collapses that have occurred offshore of Antilles arc islands and summarizes ongoing research on emplacement processes.

From homepages to network profiles : balancing personal and social identity

The World Wide Web constitutes one of the most important inventions of the late 20th century: it has changed culture, society, business, communication, politics, and many other fields of human endeavour, not least also by providing a more user-friendly pathway of access to its major underlying technology, the Internet itself. Key phases in its development can be charted, especially by how it has been used to present and share information – and here, the personal or professional, private or official homepage stands in as a useful representation of wider Web trends overall. From hand-coded beginnings through several successive stages of experimentation and standardisation, to the shifting balance between personal sites and social networks, the homepage demonstrates how the Web itself, and its place in our lives, have changed.

Uncertainty analysis of pollutant build-up modelling based on a Bayesian Weighted Least Squares approach

Reliable pollutant build-up prediction plays a critical role in the accuracy of urban stormwater quality modelling outcomes. However, water quality data collection is resource demanding compared to streamflow data monitoring, where a greater quantity of data is generally available. Consequently, available water quality data sets span only relatively short time scales unlike water quantity data. Therefore, the ability to take due consideration of the variability associated with pollutant processes and natural phenomena is constrained. This in turn gives rise to uncertainty in the modelling outcomes as research has shown that pollutant loadings on catchment surfaces and rainfall within an area can vary considerably over space and time scales. Therefore, the assessment of model uncertainty is an essential element of informed decision making in urban stormwater management. This paper presents the application of a range of regression approaches such as ordinary least squares regression, weighted least squares Regression and Bayesian Weighted Least Squares Regression for the estimation of uncertainty associated with pollutant build-up prediction using limited data sets. The study outcomes confirmed that the use of ordinary least squares regression with fixed model inputs and limited observational data may not provide realistic estimates. The stochastic nature of the dependent and independent variables need to be taken into consideration in pollutant build-up prediction. It was found that the use of the Bayesian approach along with the Monte Carlo simulation technique provides a powerful tool, which attempts to make the best use of the available knowledge in the prediction and thereby presents a practical solution to counteract the limitations which are otherwise imposed on water quality modelling.

The borate mineral jeremejevite Al6(BO3)5(F,OH)3 – A vibrational spectroscopic study

Jeremejevite is a borate mineral of aluminium and is of variable colour, making the mineral and important inexpensive jewel. The mineral contains variable amounts of F and OH, depending on origin. A comparison of the vibrational spectroscopic data is made with the published data of borate minerals. Raman spectra were averaged over a range of crystal orientations. Two intense Raman bands observed at 961 and 1067 cm−1 are assigned to the symmetric stretching and antisymmetric stretching modes of trigonal boron. Infrared spectrum, bands observed at 1229, 1304, 1350, 1388 and 1448 cm−1 are attributed to BOH in-plane bending modes. Intense Raman band found at 372 cm−1 with other bands of significant intensity at 327 and 417 cm−1 is assigned to trigonal borate bending modes. A quite intense Raman band is found at 3673 cm−1 with other sharp Raman bands found at 3521, 3625 and 3703 cm−1 are assigned to the stretching modes of OH. Raman and infrared spectroscopy has been used to assess the molecular structure of the mineral jeremejevite. Such research is important in the study of borate based nanomaterials.

Detection of excessive diesel engine piston slap using acoustic emission signals

This paper presents a study whereby a series of tests was undertaken using a naturally aspirated 4 cylinder, 2.216 litre, Perkins Diesel engine fitted with a piston having an undersized skirt. This experimental simulation resulted in engine running conditions that included abnormally high levels of piston slap occurring in one of the cylinders. The detectability of the resultant Diesel engine piston slap was investigated using acoustic emission signals. Data corresponding to both normal and piston slap engine running conditions was captured using acoustic emission transducers along with both; in-cylinder pressure and top-dead centre reference signals. Using these signals it was possible to demonstrate that the increased piston slap running conditions were distinguishable by monitoring the piston slap events occurring near the piston mid-stroke positions. However, when monitoring the piston slap events occurring near the TDC/BDC piston stroke positions, the normal and excessive piston slap engine running condition were not clearly distinguishable.

The Levels of Job Satisfaction, Stress and Burnout In Australian and New Zealand Haemodialysis Nurses

Background: Job dissatisfaction, stress and burnout is linked to high rates of nurses leaving the profession, poor morale, poor patient outcomes and increased financial expenditure. Haemodialysis nurses find their work satisfying although it can be stressful. Little is known, however, about job satisfaction, stress or burnout levels of haemodialysis nurses in Australia and New Zealand. Aims: To assess the current levels of job satisfaction, stress, burnout and nurses’ perception of the haemodialysis work environment. Methods: An observational study involved a cross-sectional sample of 417 registered or enrolled nurses working in Australian or New Zealand haemodialysis units. Data was collected using an on-line questionnaire containing demographic and work characteristics as well as validated measures of job satisfaction, stress, burnout and the work environment Results: 74% of respondents were aged over 40 and 75% had more than six years of haemodialysis nursing experience. Job satisfaction levels were comparable to studies in other practice areas with higher satisfaction derived from professional status and interactions with colleagues. Despite nurses viewing their work environment favourably, moderate levels of burnout were noted with frequent stressors related to workload and patient death and dying. Interestingly there were no differences found between the type or location of dialysis unit. Conclusion: Despite acceptable levels of job satisfaction and burnout, stress with workloads and facets of patient care were found. Understanding the factors that contribute to job satisfaction, stress and burnout can impact the healthcare system through decreased costs by retaining valued staff and through improved patient care.

Variation in leaf structure of the invasive Madeira vine (Anredera cordifolia, Basellaceae) at different light levels

Madeira vine (Anredera cordifolia (Ten.) Steenis) is a climber in the angiosperm family Basellaceae. It is native to South America and has naturalised in Australia. It is regarded as a serious environmental weed because of the structural damage it causes to native vegetation. The present study, for the first time, documents anatomical and morphological traits of the leaves of A. cordifolia and considers their implications for its ecology and physiology. Plants were grown under three different light levels, and anatomical and morphological leaf characters were compared among light levels, among cohorts, and with documented traits of the related species, Basella alba L. Stomata were present on both the adaxial and abaxial sides of the leaf, with significantly more stomata on the abaxial side and under high light. This may account for the ability of this species to fix large amounts of carbon and rapidly respond to light gaps. The leaves had very narrow veins and no sclerenchyma, suggesting a low construction cost that is associated with invasive plants. There was no significant difference in any of the traits among different cohorts, which agrees with the claim that A. cordifolia primarily propagates vegetatively. The anatomy and morphology of A. cordifolia was similar to that of B. alba.

A test of three interventions to promote people's communication of their consent for organ donation

People's decision to join an organ donor registry and have a discussion with family about their organ donation preference increases the likelihood that their family will consent to donation of their organs. This study explores the effectiveness of three interventions compared to a control condition to increase individual consent (registering and discussing donation wishes) for organ donation. Australian residents who had not previously communicated their consent (N = 177) were randomly allocated to complete an online survey representing either an extended theory of planned behaviour motivational intervention (strengthening intention via attitudes, subjective norms, control, moral norms and identity), a volitional intervention using constructs from the health action process approach (strengthening the translation of intentions into action using action plans and coping plans), a combined motivational and volitional intervention, or a control condition. Registering, but not discussing, intentions increased in the motivational compared to non-motivational conditions. For joining the organ donor registry, the combination of strengthening intentions (motivational) as well as forming specific action (when, where, how, and with whom for discussing) and coping (listing potential obstacles and how these may be overcome) plans (volitional) resulted in significantly higher rates of self-reported behaviour. There was no evidence for this effect on discussion.

Work environment, job satisfaction, stress and burnout among haemodialysis nurses

Aim To examine the relationships among nurse and work characteristics, job satisfaction, stress, burnout and the work environment of haemodialysis nurses. Background Haemodialysis nursing is characterised by frequent and intense contact with patients in a complex and intense environment. Method Cross-sectional online survey of 417 haemodialysis nurses that included nurse and work characteristics, the Brisbane Practice Environment Measure, Index of Work Satisfaction, Nursing Stress Scale and the Maslach Burnout Inventory. Results Haemodialysis nurses reported an acceptable level of job satisfaction and perceived their work environment positively, although high levels of burnout were found. Nurses who were older and had worked in haemodialysis the longest had higher satisfaction levels, experienced less stress and lower levels of burnout than younger nurses. The in-centre type of haemodialysis unit had greater levels of stress and burnout than home training units. Greater satisfaction with the work environment was strongly correlated with job satisfaction, lower job stress and emotional exhaustion. Conclusion Haemodialysis nurses experienced high levels of burnout even though their work environment was favourable and they had acceptable levels of job satisfaction. Implications for Nursing Management: Targeted strategies are required to retain and avoid burnout in younger and less experienced nurses in this highly specialised field of nursing.

Single nucleotide polymorphism in hsa-mir-196a-2 and breast cancer risk : a case control study

microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic groups.

Laboratory measurement of hydraulic conductivity functions of two unsaturated sandy soils during drying and wetting processes

The importance of applying unsaturated soil mechanics to geotechnical engineering design has been well understood. However, the consumption of time and the necessity for a specific laboratory testing apparatus when measuring unsaturated soil properties have limited the application of unsaturated soil mechanics theories in practice. Although methods for predicting unsaturated soil properties have been developed, the verification of these methods for a wide range of soil types is required in order to increase the confidence of practicing engineers in using these methods. In this study, a new permeameter was developed to measure the hydraulic conductivity of unsaturated soils using the steady-state method and directly measured suction (negative pore-water pressure) values. The apparatus is instrumented with two tensiometers for the direct measurement of suction during the tests. The apparatus can be used to obtain the hydraulic conductivity function of sandy soil over a low suction range (0-10 kPa). Firstly, the repeatability of the unsaturated hydraulic conductivity measurement, using the new permeameter, was verified by conducting tests on two identical sandy soil specimens and obtaining similar results. The hydraulic conductivity functions of the two sandy soils were then measured during the drying and wetting processes of the soils. A significant hysteresis was observed when the hydraulic conductivity was plotted against the suction. However, the hysteresis effects were not apparent when the conductivity was plotted against the volumetric water content. Furthermore, the measured unsaturated hydraulic conductivity functions were compared with predictions using three different predictive methods that are widely incorporated into numerical software. The results suggest that these predictive methods are capable of capturing the measured behavior with reasonable agreement.

Infrared and Raman spectroscopic characterization of the arsenate mineral ceruleite Cu2Al7(AsO4)4(OH)13⋅11.5(H2O)

The molecular structure of the arsenate mineral ceruleite has been assessed using a combination of Raman and infrared spectroscopy. The most intense band observed at 903 cm-1 is assigned to the (AsO4)3- symmetric stretching vibrational mode. The infrared spectrum shows intense bands at 787, 827 and 886 cm-1, ascribed to the triply degenerate m3 antisymmetric stretching vibration. Raman bands observed at 373, 400, 417 and 430 cm-1 are attributed to the m2 vibrational mode. Three broad bands for ceruleite found at 3056, 3198 and 3384 cm-1 are assigned to water OH stretching bands. By using a Libowitzky empirical equation, hydrogen bond distances of 2.65 and 2.75 Å are calculated. Vibrational spectra enable the molecular structure of the ceruleite mineral to be determined and whilst similarities exist in the spectral patterns with the roselite mineral group, sufficient differences exist to be able to determine the identification of the minerals.

Project governance : ethical decision making in project procurement in the Malaysian public sectors

Managing public sector projects in Malaysia is a unique challenge. This is because of the ethical issues involved during the project procurement process. These ethical issues need attention because they will have an impact on the quality, cost and time of the project itself. The ethical issues here include conflict of interest, bid shopping, collusive tendering, bid cutting, corruption and the payment game. In 2006, 17.3% of 417 Malaysian government contract projects were considered sick due to contractors' performances that failed to conduct the project according to the project plan. Some of the sick projects from these statistics are due to the ethical issues involved. These construction projects have low quality due to the selection of the contractors, done unethically due to personal relationships instead of professional qualifications. That is why it is important to govern the project procurement processes to ensure the accountability and transparency of the decision making process to ensure that these ethical issues can be avoided. Extensive research has been conducted on the ethical issues in the tendering process or the award phase of project management. There is a lack of studies looking at the role of clients, including the government client, in relation to unethical practice in project procurement in the public sector. It is important to understand that ethical issues not only involve the contractors and suppliers but also the clients. Even though there are codes of ethics in the public sectors, ethical issues still arise. Therefore, this research develops a project governance framework (PGEDM) for ethical decision making in the Malaysian public sectors. This framework combines the ethical decision making process together with the project governance principals in guiding the public sectors with ethical decision making in project procurement. A triangulation of questionnaire survey and Delphi study was employed in this research to collect required qualitative and quantitative data. A questionnaire survey was conducted among the public officials (the practitioners) who are currently working in the procurement area in the Malaysian public sectors, in identifying the ethical behaviours and factors influencing further ethical behaviour to occur. A Delphi study was also conducted with the assistance of a panel of experts consisting of practitioners that have expertise in the area of project governance and project procurement as well as academician, which further considered the relationship and the influence of the criteria and indicators of ethical decision making (EDM) and project governance (project criteria, organisational culture, contract award criteria, individual criteria, client's requirements, government procedures and professional ethics). Through the identification and integration of the factors and EDM criteria as well as the project governance criteria and EDM steps for ethical issues, a PGEDM framework was developed to promote, and drive consistent decision outcome in project procurement in the public sector. The framework contributes significantly to ethical decision making in the project procurement process. These findings not only give benefit to the people involved in project procurement but also to the public officials in guiding them to be more accountable in handling ethical issues in the future and to have a more transparent decision making process.