Long-evans rats acquire operant self-administration of 20% ethanol without sucrose fading

A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume two times more ethanol than those given continuous access without the use of water deprivation or sucrose fading (5-6 g/kg every 24 h vs 2-3 g/kg every 24 h, respectively). In this study, we have adapted the model to an operant self-administration paradigm. Long-Evans rats were given access to 20% ethanol in overnight sessions on one of two schedules: (1) intermittent (Monday, Wednesday, and Friday) or (2) daily (Monday through Friday). With the progression of the overnight sessions, both groups showed a steady escalation in drinking (3-6 g/kg every 14 h) without the use of a sucrose-fading procedure. Following the acquisition phase, the 20% ethanol groups consumed significantly more ethanol than did animals trained to consume 10% ethanol with a sucrose fade (1.5 vs 0.7 g/kg every 30 min) and reached significantly higher blood ethanol concentrations. In addition, training history (20% ethanol vs 10% ethanol with sucrose fade) had a significant effect on the subsequent self-administration of higher concentrations of ethanol. Administration of the pharmacological stressor yohimbine following extinction caused a significant reinstatement of ethanol-seeking behavior. Both 20% ethanol models show promise and are amenable to the study of maintenance, motivation, and reinstatement. Furthermore, training animals to lever press for ethanol without the use of sucrose fading removes a potential confound from self-administration studies. © 2010 Nature Publishing Group All rights reserved.

Clinical strategies for the alleviation of contractures from a predictive mathematical model of dermal repair

Hypertrophic scars arise when there is an overproduction of collagen during wound healing. These are often associated with poor regulation of the rate of programmed cell death(apoptosis) of the cells synthesizing the collagen or by an exuberant inflammatory response that prolongs collagen production and increases wound contraction. Severe contractures that occur, for example, after a deep burn can cause loss of function especially if the wound is over a joint such as the elbow or knee. Recently, we have developed a morphoelastic mathematical model for dermal repair that incorporates the chemical, cellular and mechanical aspects of dermal wound healing. Using this model, we examine pathological scarring in dermal repair by first assuming a smaller than usual apoptotic rate for myofibroblasts, and then considering a prolonged inflammatory response, in an attempt to determine a possible optimal intervention strategy to promote normal repair, or terminate the fibrotic scarring response. Our model predicts that in both cases it is best to apply the intervention strategy early in the wound healing response. Further, the earlier an intervention is made, the less aggressive the intervention required. Finally, if intervention is conducted at a late time during healing, a significant intervention is required; however, there is a threshold concentration of the drug or therapy applied, above which minimal further improvement to wound repair is obtained.

Catalytic properties of 26 S and 20 S proteasomes and radiolabeling of MB1, LMP7, and C7 subunits associated with trypsin-like and chymotrypsin-like activities*

20 and 26 S proteasomes were isolated from rat liver. The procedure developed for the 26 S proteasome resulted in greatly improved yields compared with previously published methods. A comparison of the kinetic properties of 20 and 26 S proteasomes showed significant differences in the kinetic characteristics with certain substrates and differences in the effects of a protein substrate on peptidase activity. Observed differences in the kinetics of peptidylglutamyl peptide hydrolase activity suggest that the 26 S complex cannot undergo the conformational changes of 20 S proteasomes at high concentrations of the substrate benzyloxycarbonyl (Z) -Leu-Leu-Glu-b-naphthylamide. Various inhibitors that differentially affect the trypsin-like and chymotrypsin-like activities have been identified. Ala-Ala-Phe-chloromethyl (CH2Cl) inhibits chymotrypsin-like activity assayed with succinyl (Suc) -Leu-Leu-Val-Tyr-AMC, but surprisingly not hydrolysis of Ala-Ala-Phe-7-amido-4-methylcoumarin (AMC). Tyr-Gly-Arg-CH2Cl inhibits Suc-Leu-Leu-Val-Tyr-AMC hydrolysis as well as trypsinlike activity measured with t-butoxycarbonyl (Boc) -Leu-Ser-Thr-Arg-AMC, while Z-Phe-Gly-Tyr-diazomethyl (CHN2) was found to inhibit only the two chymotrypsin- like activities. Radiolabeled forms of peptidyl chloromethane and peptidyl diazomethane inhibitors, [3H]acetyl-Ala-Ala-Phe-CH2Cl, [3H]acetyland radioiodinated Tyr-Gly-Arg-CH2Cl, and Z-Phe-Gly- Tyr-(125I-CHN2), have been used to identify catalytic components associated with each of the three peptidase activities. In each case, incorporation of the label could be blocked by prior treatment of the proteasomes with known active site-directed inhibitors, calpain inhibitor 1 or 3,4-dichloroisocoumarin. Subunits of labeled proteasomes were separated either by reverse phase-HPLC and SDS-polyacrylamide gel electrophoresis or by twodimensional polyacrylamide gel electrophoresis followed by autoradiography/fluorography and immunoblotting with subunit-specific antibodies. In each case, label was found to be incorporated into subunits C7, MB1, and LMP7 but in different relative amounts depending on the inhibitor used, consistent with the observed effects on the different peptidase activities. The results strongly suggest a relationship between trypsin-like activity and chymotrypsin-like activity. They also help to relate the different subunits of the complex to the assayed multicatalytic endopeptidase activities

The evolution of QUT’s Student Success Program : 20,000 students later

“The Student Success Program (SSP) is a monitoring and early intervention program in operation at QUT designed to identify and support those students deemed to be at risk of disengaging for their learning and their institution” (Nelson, Quinn, Marrington & Clarke, 2011, p. 83). This report reflects on the development of the program since its inception in 2007. In acknowledging similar initiatives within the sector that monitor student learning engagement, the Nuts & Bolts session allows for identification and discussion of the critical success factors for these intervention and support programs.

Reflection in Integrated Problem Based Learning : 20 years of continuing application to the teaching of architecture

In 1984 the School of Architecture and Built Environment within the University of Newcastle, Australia introduced an integrated program based on real design projects and using Integrated Problem Based Learning (IPBL) as the teaching method. Since 1984 there have been multiple changes arising from the expectations of the architectural fraternity, enrolling students, lecturers, available facilities, accreditation authorities and many others. These challenges have been successfully accommodated whilst maintaining the original purposes and principles of IPBL. The Architecture program has a combined two-degree structure consisting of a first degree, Bachelor of Science (Architecture), followed by a second degree, Bachelor of Architecture. The program is designed to simulate the problem-solving situations that face a working architect in every day practice. This paper will present the degree structure where each student is enrolled in a single course per semester incorporating design integration and study areas in design studies, professional studies, historical studies, technical studies, environmental studies and communication skills. Each year the design problems increase in complexity and duration set around an annual theme. With 20 years of successful delivery of any program there are highlights and challenges along the way and this paper will discuss some of the successes and barriers experienced within the School of Architecture and Built Environment in delivering IPBL. In addition, the reflective process investigates the currency of IPBL as an appropriate vehicle for delivering the curriculum in 2004 and any additional administrative or staff considerations required to enhance the continuing application of IPBL.

Prosecutorial discretion in assisted dying in Canada : a proposal for charging guidelines

An Expert Panel of the Royal Society of Canada and a Select Committee of the Québec National Assembly both recently recommended the issuance of permissive guidelines for the exercise of prosecutorial discretion on voluntary euthanasia and assisted suicide and “medical aid in dying” respectively. It seems timely, therefore, to propose a set of offence-specific guidelines for how prosecutorial discretion should be exercised in cases of voluntary euthanasia and assisted suicide in Canadian provinces and territories. We take as our starting point the only existing guidelines of this sort currently in force in the world (i.e. the British Columbia Guidelines, and the England and Wales Guidelines). In light of certain concerns we have with these guidelines, we outline an approach to constructing guidelines for Canadian jurisdictions that begins with identifying three guiding principles we argue are appropriate for this purpose (respect for autonomy, the need for high-quality prosecutorial decision making, and the importance of public confidence in that decision making), and ends with a concrete and detailed set of proposed guidelines. The paper is consistent with, but also extends, the work of the Royal Society of Canada Expert Panel on End of Life Decision Making. Un panel d’expert de la Société Royale du Canada et une Commission spéciale de l’Assemblée nationale du Québec ont tous les deux récemment recommandé que soit émises des directives permettant exercice d’un pouvoir de poursuite discrétionnaire concernant l’euthanasie et le suicide assisté et « l’assistance médicale pour mourir », respectivement. Il semble donc à propos de proposer une série de directives spécifiques aux offenses sur la façon dont le pouvoir de poursuite discrétionnaire dans les territoires et provinces canadiennes serait appliqué dans les cas d’euthanasie et de suicide assisté. Nous avons pris comme point de départ les seules directives de la sorte existant déjà (c’est-à-dire celle de la Colombie-Britannique et de l’Angleterre et du Pays de Galles). Par contre, compte tenu de certaines de nos réserves concernant ces directives, nous avons ensuite établi les grandes lignes d’une approche permettant de mettre sur pied des directives pour les juridictions canadiennes, qui débute par l’identification de trois principes de base qui sont selon nous appropriées à cette fin (respect de l’autonomie, besoin pour une grande qualité de prise de prise de décision du poursuivant et la confiance du public envers cette prise de décision) pour se terminer par une série de directives concrètes et détaillées. Le présent document est compatible avec le travail de la Société royale du Canada tout en en augmentant la portée.

Social and environmental accounting research : major contributions and future directions for developing countries

A review is provided of major contributions in social and environmental accounting literature focusing on the issues of developing countries. The review of prior research shows that the major contributions have been related to the motivations for social and environmental disclosure. However, other important research areas such as ethical/accountability issues and how to cost externalities which have already been considered within the developing country context. Contemporary social and environmental issues such as climate change and greenhouse gas emissions affecting the global community also appear to be key issues of research to scholars in both developed and developing countries. Finally, some future research directions are identified.

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Phase composition of the rapidly quenched melt of YBa2Cu3O7-y+20 mol% Y2BaCuO5

Samples of YBa2Cu3O7-y+20 mol% Y2BaCuO5, with thicknesses ranging between 50-250 μm, have been melt processed and rapidly quenched from temperatures between 985 and 1100°C by immersing them in liquid nitrogen. The phase composition and microstructures of these samples have been characterised using a combination of X-ray diffractometry, optical microscopy and scanning electron microscopy with energy dispersive X-ray spectroscopy. The quenched melt of samples quenched from temperatures greater than 985°C appears relatively homogeneous but consists of Ba2Cu3Ox (BC1.5) and BaCu2O2 (BC2) regions. At about 985°C, BaCuO2 (BC1) crystallises from the melt and most of the BC1.5 decomposes into BC1 and CuO or into BC1 and BC2. The crystallisation of BC1 induces segregation of elements in the melt and this is very significant for the melt texturing of YBCO.

Phase evolution of the quenched melt of YBa2Cu3O7-y with 20 mol% Y2BaCuO5 additions

Samples of YBa2Cu3O7-y + 20 mol% Y2BaCuO5 have been melt processed and quenched from temperatures ranging from 975 to 1100°C. The microstructure of the samples have been characterized via a combination of x-ray diffractometry, optical microscopy, scanning electron microscopy, energy dispersive x-ray spectrometry and wavelength dispersive x-ray spectrometry. BaCuO2 (BC1) and BaCu2O2 (BC2) crystallize from the melt of samples quenched from temperatures between 985 and 1100°C in air. The average yttrium content differs for BC1 and BC2, and it is 4.3 and 5.1 at.%, respectively. Holding times of 20 hours at temperatures above or equal to 1040°C give rise to a dendritic pattern of BC1 surrounded by BC2. The complex changes of the nature of the melt as a function of temperature and time are likely to play a significant role in the mechanism of melt texturing.

IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF

Background IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. Methods The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined. Results The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p < 0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p < 0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level. Conclusions This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment. © 2011 Elsevier Ltd. All rights reserved.

Information systems success research : the “20-year update?” panel report from PACIS, 2011

This article summarizes a panel held at the 15th Pacific Asia Conference on Information Systems (PACIS) in Brisbane, Austrailia, in 2011. The panelists proposed a new research agenda for information systems success research. The DeLone and McLean IS Success Model has been one of the most influential models in Information Systems research. However, the nature of information systems continues to change. Information systems are increasingly implemented across layers of infrastructure and application architecture. The diffusion of information systems into many spheres of life means that information systems success needs to be considered in multiple contexts. Services play a much more prominent role in the economies of countries, making the “service” context of information systems increasingly important. Further, improved understandings of theory and measurement offer new opportunities for novel approaches and new research questions about information systems success.

Outsourcing income tax returns : convenient and/or controversial

This paper investigates the outsourcing of income tax return preparation by Australian accounting firms. It identifies the extent to which firms are currently outsourcing accounting services or considering outsourcing accounting services, with a focus on personal and business income tax return preparation. The motivations and barriers for outsourcing by Australian accounting firms are also considered in this paper. Privacy, security of client data, and the competence of the outsourcing provider's staff have been identified as risks associated with outsourcing. An expectation relating to confidentiality of client data is also examined in this paper. Statistical analysis of data collected from a random sample of Australian accounting firms using a survey questionnaire provided the empirical data for the paper. The results indicate that the majority of Australian accounting firms are either currently outsourcing or considering outsourcing accounting services, and firms are outsourcing taxation preparation both onshore and offshore. The results also indicate that firms expect the volume of outsourced work to increase in the future. In contrast to the literature identifying labour arbitrage as the primary driver for organisations choosing to outsource, this study found that the main factors considered by accounting firms in the decision to outsource were to expedite delivery of services to clients and to enable the firm to focus on core competencies. Data from this study also supports the literature which ndicates that not all tax practitioners are adhering to codes of conduct in relation to client confidentiality. Research identifying the extent to which accounting services are outsourced is limited, therefore significant contributions to the academic literature and the accounting profession are provided by this ndicates that not all tax practitioners are adhering to codes of conduct in relation to client confidentiality. Research identifying the extent to which accounting services are outsourced is limited, therefore significant contributions to the academic literature and the accounting profession are provided by this study.

Artemisinin induced dormancy in Plasmodium falciparum : duration, recovery rates and implications in treatment failure

Background Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Methods Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Results Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an ∼10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. Conclusions These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

20 Years of pacifying responses to environmental management

Using a state, pressure, response framework, we provide an evidence-based reflection on environmental outcomes in Australia and New Zealand across the domains of climate change, biodiversity, freshwater and marine management, emphasising the role of Indigenous and business perspectives. Significant developments have occurred in the past 20 years through affirmation of Indigenous rights and responsibilities. Responses to climate change have tended to emphasise passive risk management with unclear outcomes. Despite meeting biodiversity protection targets, outcomes are worsening, suggesting a need to challenge the dualistic preservation/production land categorisations. In freshwater and marine management, a mix of collaborative and market-based responses has emerged, although their efficacy remains untested. A reliance on voluntary approaches by business makes critical assessment of progress difficult. Thus, despite strong progress in some areas, the adaptiveness of environmental management remains limited, and many indicators suggest continuing decline in environmental condition. Our responses have been largely pacifying in nature, leading to perverse outcomes and failure to acknowledge alternatives that might address deteriorating environmental conditions. A shift is needed towards deliberative policy experimentation that truly values the application of novel and diversified approaches and facilitates integrated learning across environmental domains.