MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin

Soluble endoglin is an anti-angiogenic protein that is released from the placenta and contributes to both maternal endothelial dysfunction and the clinical features of severe preeclampsia. The mechanism through which soluble endoglin is released from the placenta is currently unknown; however, recent work in colorectal cancer identified matrix metalloproteinase 14 (MMP-14) as the cleavage protease of endoglin. To determine whether this is also the mechanism responsible for soluble endoglin release in preeclampsia, we investigated the expression of MMP-14 within the placenta and the effects of its inhibition on soluble endoglin release. Placentas were obtained from severe, early onset preeclamptic pregnancies (n = 8) and gestationally matched preterm controls (n = 8). MMP-14 was predominately localized to the syncytiotrophoblast. Results from a proximity ligation assay showed protein interactions between endogenous MMP-14 and endoglin within the preeclamptic placenta. To demonstrate that this interaction produces soluble endoglin, we treated trophoblastic BeWo cells with either a broad-spectrum MMP inhibitor (GM6001) or MMP-14 siRNA. Both treatments produced a decrease in soluble endoglin (P ≤ 0.05). Treatment of mice bearing BeWo xenografts with GM6001 decreased circulating soluble endoglin levels in mouse serum (P ≤ 0.05). These findings indicate that MMP-14 is the likely cleavage protease of endoglin in the setting of preeclampsia. This approach provides a novel method for the development of potential therapeutics to reduce circulating soluble endoglin and ameliorate the clinical features of severe preeclampsia.

NADPH oxidases as regulators of tumor angiogenesis : current and emerging concepts

Significance Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and peroxynitrite are generated ubiquitously by all mammalian cells and have been understood for many decades as inflicting cell damage and as causing cancer by oxidation and nitration of macromolecules, including DNA, RNA, proteins, and lipids. Recent Advances A current concept suggests that ROS can also promote cell signaling pathways triggered by growth factors and transcription factors that ultimately regulate cell proliferation, differentiation, and apoptosis, all of which are important hallmarks of tumor cell proliferation and angiogenesis. Moreover, an emerging concept indicates that ROS regulate the functions of immune cells that infiltrate the tumor environment and stimulate angiogenesis, such as macrophages and specific regulatory T cells. Critical Issues In this article, we highlight that the NADPH oxidase family of ROS-generating enzymes are the key sources of ROS and, thus, play an important role in redox signaling within tumor, endothelial, and immune cells thereby promoting tumor angiogenesis. Future Directions Knowledge of these intricate ROS signaling pathways and identification of the culprit NADPH oxidases is likely to reveal novel therapeutic opportunities to prevent angiogenesis that occurs during cancer and which is responsible for the revascularization after current antiangiogenic treatment.

Case Study 4: Education Doctoral Student - "An Exploratory Study of Online Social Networking within a Doctorate of Education Program"

Introduction The professional doctorate is specifically designed for professionals investigating real-world problems and relevant issues for a profession, industry, and/or the community. The focus is scholarly research into professional practices. The research programme bridges academia and the professions, and offers doctoral candidates the opportunity to investigate issues relevant to their own practices and to apply these understandings to their professional contexts. The study on which this article is based sought to track the scholarly skill development of a cohort of professional doctoral students who commenced the course in January 2008 at an Australian university. Because they hold positions of responsibility and are time-poor, many doctoral students have difficulty transitioning from professional practitioner to researcher and scholar. The struggle many experience is in the development of a theoretical or conceptual standpoint for argumentation (Lesham, 2007; Weese et al., 1999). It was thought that the use of a scaffolded learning environment that drew upon a blended learning approach incorporating face to face intensive blocks and collaborative knowledge-building tools such as wikis would provide a data source for understanding the development of scholarly skills. Wikis, weblogs and similar social networking software have the potential to support communities to share, learn, create and collaborate. The development of a wiki page by each candidate in the 2008 cohort was encouraged to provide the participants and the teaching team members with textual indicators of progress. Learning tasks were scaffolded with the expectation that the candidates would complete these tasks via the wikis. The expectation was that cohort members would comment on each other’s work, together with the supervisor and/or teaching team member who was allocated to each candidate. The supervisor is responsible for supervising the candidate’s work through to submission of the thesis for examination and the teaching team member provides support to both the supervisor and the candidate through to confirmation. This paper reports on the learning journey of a cohort of doctoral students during the first seven months of their professional doctoral programme to determine if there had been any qualitative shifts in understandings, expectations and perceptions regarding their developing knowledge and skills. The paper is grounded in the literature pertaining to doctoral studies and examines the structure of the professional doctoral programme. Following this is a discussion of the qualitative study that helped to unearth key themes regarding the participants’ learning journey.

Graphene-based supercapacitor with carbon nanotube film as highly efficient current collector

Flexible graphene-based thin film supercapacitors were made using carbon nanotube (CNT) films as current collectors and graphene films as electrodes. The graphene sheets were produced by simple electrochemical exfoliation, while the graphene films with controlled thickness were prepared by vacuum filtration. The solid-state supercapacitor was made by using two graphene/CNT films on plastic substrates to sandwich a thin layer of gelled electrolyte. We found that the thin graphene film with thickness <1 μm can greatly increase the capacitance. Using only CNT films as electrodes, the device exhibited a capacitance as low as ~0.4 mF cm−2, whereas by adding a 360 nm thick graphene film to the CNT electrodes led to a ~4.3 mF cm−2 capacitance. We experimentally demonstrated that the conductive CNT film is equivalent to gold as a current collector while it provides a stronger binding force to the graphene film. Combining the high capacitance of the thin graphene film and the high conductivity of the CNT film, our devices exhibited high energy density (8–14 Wh kg−1) and power density (250–450 kW kg−1).

Three essays on banks trading activities

With a fair share of the blame for the subprime crisis pointing to banks' extensive involvement in trading, this thesis examines three closely related issues. The first essay shows that regulatory capital arbitrage, insolvency risk, and non-interest income are all important motivations for banks to become involved in trading. The second essay support the widely held perception that trading activities such as off-balance sheet derivatives, securitization, and assets sales all are making banks more opaque. With banks' business model changing from ''originate and hold'' to ''originate, repackage, and sell'', the last essay show that trading channel exist and it has weakened the effectiveness of monetary policy transmission through banks' capital and lending channel.

Take me to your employer: the organisational reach of occupational health and safety regulation

[Conclusion] We have explored two dimensions of the Australian OHS statutes which enable statutory OHS duties to reach more than one employer or self-employed person within a corporate group or network. First, most of the OHS statutes contain provisions extending the reach of employer’s duty beyond the employer’s employees. One legislative technique is to deem contractors and their employees to be employees of the principal contractor. Another imposes duties on employers and self-employed persons to persons who are not employees, so that employers and self-employed persons can be responsible for the OHS of firms, and those they engage, lower in the contractual chain. These duties are non-delegable, meaning that the principal contractor cannot seek to delegate OHS duties to firms lower in the contractual chain. Second, new Victorian ‘shadow officer’ provisions can be applied to remove difficulties and doubt as to the liability of partners in a partnership, officers of unincorporated associations, joint venturers, and holding and subsidiary companies within corporate groups. While the provisions can be argued simply to confirm that a partner who fails to take reasonable care in relation to OHS will be guilty of an offence, we demonstrate that there are very real benefits to having ‘shadow officer’ provisions which remove uncertainties about the liability of unincorporated associations, joint ventures and corporate groups. Perhaps most significantly, the Victorian corporate officer provisions have the potential to extend liability to individuals and other entities within organisational structures, where those individuals and entities make or participate in making decisions that affect the whole or a substantial part of the organisation’s business, and are responsible for an OHS offence having been committed, due to their failure to take reasonable care. We suggest that similar provisions should be included in all OHS statutes, to overcome at least some of the barriers limiting group responsibility for OHS statutory duties.

Australian health and safety inspectors’ perceptions and actions in relation to changed work arrangements

Extensive international research points to an association between changed work arrangements, especially those commonly labelled as contingent work, with adverse occupational health and safety (OHS) outcomes. Research also indicates these work arrangements have weakened or bypassed existing OHS and workers’ compensation regulatory regimes. However, there has been little if any research into how OHS inspectors perceive these issues and how they address them during workplace visits or investigations. Between 2003 and 2007 research was undertaken that entailed detailed documentary and statistical analysis, extended interviews with 170 regulatory managers and inspectors, and observational data collected while accompanying inspectors on 118 ‘typical’ workplace visits. Key findings are that inspectors responsible for a range of industries see altered work arrangements as a serious challenge, especially labour hire (agency work) and subcontracting. Though the law imposes clear obligations, inspectors identified misunderstanding/blameshifting and poor compliance amongst parties to these arrangements. The complexity of these work arrangements also posed logistical challenges to inspectorates.

Development of a new regulatory model for occupational health and safety in the New South Wales coal industry: an issues paper for the New South Wales Department of Mineral Resources

This paper addresses the regulatory issues arising in developing a new regulatory model for the New South Wales Coal Industry. As such, it identifies the relevant literature on this subject, the options available for reform, and the experience of Australian and key international bodies responsible for the development of regulatory standards in this area. In particular it: Identifies the main shortcomings in the existing regulatory approach; Identifies the potential roles/main strengths and weaknesses of different types of standards (eg specification, performance, process and systems-based rules) and potential “best practice’ combinations of standards; Examines the appropriateness of the current regulatory regime whereby the general OHS legislation (including the general duty provisions) applies to mining in addition to the large body of regulation which is specific to mining; Identifies the importance of, and possible means of addressing, issues of worker participation within the coal mining industry; Draws on the literature on what motivates companies and individuals for the purpose of recommending key provisions for inclusion in new legislation to provide appropriate personal and organisational incentives; Draws on the literature on major hazards facilities to suggest the appropriate roles for OHS management systems and safety reports or comparable approaches (eg mine safety management plans); Draws on the United Kingdom (UK) and United States of America (USA) experience of coal mine safety and its regulation for comparative purposes, and for insights as to what sort of regulation most effectively reduces work related injury and disease in coal mining; Examines the relevant roles of International Labour Organisation (ILO) Conventions; Examines the extent to which different regulatory regimes would be appropriate to open cut and underground coal mining; and Examines options for reform. This paper is focussed specifically on the issues identified above.

La Niña : we knew it was coming, and it’s not going away

"The major La Niña climate event responsible for record flooding in Queensland  - and the largest ever cyclone to hit Australia in Yasi  —  is not over yet according to a senior climatologist at Britain’s Met office."

Social Justice Impacts of the Resources Boom

Until the 1970s mining leases were issued by state governments subject to conditions that companies build or substantially finance local community infrastructure, including housing, streets, transport, schools, hospitals and recreation facilities. Townships and communities went hand in hand with mining development. However, in the past thirty years mining companies have moved progressively to an expeditionary strategy for natural resources extraction - operating a continuous production cycle of 12 hour shifts - increasingly reliant on non-resident, fly-in, fly-out or drive-in, drive-out (FIFO/DIDO) workers who typically work block rosters, reside in work camps adjacent to existing communities and travel large distances from their homes. This paper presents the key findings of our survey into the social impacts of this kind of mining development in Qld. Based on the results we argue that the social license to develop new mining projects is strong for projects requiring a 25% or less non-resident workforce, diminishes significantly thereafter and is very weak for projects planning to recruit a non-resident workforce in excess of 75%. This finding is significant because there are at least 67 new mining projects undergoing social impact assessment in Queensland, and many it appears are planning to hire significant proportions of non-resident workers. The paper considers the policy implications of this growing social justice issue concluding there is a clear need for national leadership in formulating a national policy framework for guiding socially responsible and sustainable mining development into the next millennium.

Detection of DNA mutations using novel SERS (Surface-Enhanced Raman Spectroscopy) diagnostic platform

This article describes the detection of DNA mutations using novel Au-Ag coated GaN substrate as SERS (surface-enhanced Raman spectroscopy) diagnostic platform. Oligonucleotide sequences corresponding to the BCR-ABL (breakpoint cluster region-Abelson) gene responsible for development of chronic myelogenous leukemia were used as a model system to demonstrate the discrimination between the wild type and Met244Val mutations. The thiolated ssDNA (single-strand DNA) was immobilized on the SERS-active surface and then hybridized to a labeled target sequence from solution. An intense SERS signal of the reporter molecule MGITC was detected from the complementary target due to formation of double helix. The SERS signal was either not observed, or decreased dramatically for a negative control sample consisting of labeled DNA that was not complementary to the DNA probe. The results indicate that our SERS substrate offers an opportunity for the development of novel diagnostic assays.

An organization of visual and auditory fear conditioning in the lateral amygdala

Pavlovian fear conditioning is an evolutionary conserved and extensively studied form of associative learning and memory. In mammals, the lateral amygdala (LA) is an essential locus for Pavlovian fear learning and memory. Despite significant progress unraveling the cellular mechanisms responsible for fear conditioning, very little is known about the anatomical organization of neurons encoding fear conditioning in the LA. One key question is how fear conditioning to different sensory stimuli is organized in LA neuronal ensembles. Here we show that Pavlovian fear conditioning, formed through either the auditory or visual sensory modality, activates a similar density of LA neurons expressing a learning-induced phosphorylated extracellular signal-regulated kinase (p-ERK1/2). While the size of the neuron population specific to either memory was similar, the anatomical distribution differed. Several discrete sites in the LA contained a small but significant number of p-ERK1/2-expressing neurons specific to either sensory modality. The sites were anatomically localized to different levels of the longitudinal plane and were independent of both memory strength and the relative size of the activated neuronal population, suggesting some portion of the memory trace for auditory and visually cued fear conditioning is allocated differently in the LA. Presenting the visual stimulus by itself did not activate the same p-ERK1/2 neuron density or pattern, confirming the novelty of light alone cannot account for the specific pattern of activated neurons after visual fear conditioning. Together, these findings reveal an anatomical distribution of visual and auditory fear conditioning at the level of neuronal ensembles in the LA.

Beyond equivalency: Repositioning artistic research within the Australian university sector

Presented in concept at the ACUADS 2008 conference, this paper reports on a research study conducted for PhD into how artistic researchers have been accommodated in the Australian university research management system, and the impacts experienced by artistic researchers through this location. It draws upon a wide range of data to provide the first analysis of this topic reported across all artistic disciplines in Australia in relation to university experiences and updates the Strand Report in 1998 in relation to government policy. Data sources include a correlation of literature from arts disciplines with that of higher education management and government policies; survey responses from of heads of academic units containing artistic researchers in over 40% of Australian universities; interviews with 27 artistic researchers in three case study universities; and interviews with longstanding expert commentators on artistic research and Deputy Vice Chancellors responsible for research. The study suggests that while limited progress has been made towards the acceptance of artistic research as an equivalent and legitimate research endeavour, significant structural, cultural and practical challenges remain which are undermining relationships between universities and their artistic staff and engendering behavioural changes within artistic practitioners that can affect the nature and quality of artistic work that is produced. Reflecting the voices of artistic researchers across the broad visual and performing arts disciplinary spectrum from early to senior career academics, it explores ways forward for universities, and artistic researchers themselves, to secure greater equity and recognition for artistic research.

Prevention of Pollution of the Marine Environment from Vessels : The Potential and Limits of the International Maritime Organisation

--Critically discusses the role of International Maritime Organization (IMO) in the protection of the marine environment --Presents a clear, updated, concise and critical overview of the IMO marine environmental legal instruments --A fresh outlook on the north-south tensions in the IMO marine environmental discourses --Critically examines the principle of common but differentiated responsibilities in the context of IMO This book examines the role of The International Maritime Organization (IMO) in the prevention and control of pollution of the marine environment from vessels with a particular reference to the current north-south tensions regarding the strategy for combating climate change in the maritime sector as well as the prevention of marine pollution from the ship-breaking industry. The IMO, a United Nations specialized agency, has been entrusted with the duty to provide machinery for cooperation among governments for the prevention and control of pollution of the marine environment from vessels. The organization is responsible for drafting legal instruments as well as for facilitating technical cooperation for the protection of the marine environment. Although IMO legal instruments are mainly targeted at the prevention of pollution of the marine environment from vessels, there is a trend towards a liberal interpretation of this, and the organization has expanded its work to areas like shipbreaking, which is essentially a land-based industry.

The effects of geochemical conditions on the establishment and growth of mangrove seedlings in acid sulfate soil environments

Acid sulfate soils (ASS) is a stress factor that is responsible for the failure of some mangrove restoration projects, including abandoned aquaculture ponds converted from mangrove ecosystems. Through experimental and field studies, this research provides a better understanding of the biogeochemistry of ASS disturbance and the response of mangrove seedlings (Rhizophoraceae) under high metal levels and acidic conditions. This study found that mangrove restorations under ASS disturbance can work but with lower numbers of survived seedlings. To prevent toxicity under high levels of metal, seedlings retained metals in their roots and sparingly distributed them into aerial parts with low mobility. The presence of high levels of potential acidity parameters would allow pyrite to oxidise, thus increasing metal levels and acidity, which in turn affected the survival and growth of the seedlings.