Gemcitabine reactivates epigenetically silenced genes and functions as a DNA methyltransferase inhibitor

Gemcitabine is indicated in combination with cisplatin as first-line therapy for solid tumours including non-small cell lung cancer (NSCLC), bladder cancer and mesothelioma. Gemcitabine is an analogue of pyrimidine cytosine and functions as an anti-metabolite. Structurally, however, gemcitabine has similarities to 5-aza-2-deoxycytidine (decitabine/Dacogen®), a DNA methyltransferase inhibitor (DNMTi). NSCLC, mesothelioma and prostate cancer cell lines were treated with decitabine and gemcitabine. Reactivation of epigenetically silenced genes was examined by RT-PCR/qPCR. DNA methyltransferase activity in nuclear extracts and recombinant proteins was measured using a DNA methyltransferase assay, and alterations in DNA methylation status were examined using methylation-specific PCR (MS-PCR) and pyrosequencing. We observe a reactivation of several epigenetically silenced genes including GSTP1, IGFBP3 and RASSF1A. Gemcitabine functionally inhibited DNA methyltransferase activity in both nuclear extracts and recombinant proteins. Gemcitabine dramatically destabilised DNMT1 protein. However, DNA CpG methylation was for the most part unaffected by gemcitabine. In conclusion, gemcitabine both inhibits and destabilises DNA methyltransferases and reactivates epigenetically silenced genes having activity equivalent to decitabine at concentrations significantly lower than those achieved in the treatment of patients with solid tumours. This property may contribute to the anticancer activity of gemcitabine.

Aboriginality and the Northern Territory intervention

This thesis examines the construction of Aboriginality in recent public policy reasoning through identifying representations deployed by architects and supporters of the Commonwealth’s 2007 Northern Territory Emergency Response (the intervention). Debate about the Northern Territory intervention was explicitly situated in relation to a range of ideas about appropriate Government policy towards Indigenous people, and particularly about the nature, role, status, value and future of Aboriginality and of Aboriginal people and Torres Strait Islanders. This project involves analysis of constructions of Aboriginality deployed in texts created and circulated to explain and justify the policy program. The aim of the project is to identify the ideas about Aboriginality deployed by the intervention’s architects and supporters, and to examine the effects and implications of these discourses for political relationships between Indigenous people and settlers in Australia. This thesis will argue that advocates of the Northern Territory intervention construct Aboriginality in a range of important ways that reassert and reinforce the legitimacy of the settler colonial order and the project of Australian nationhood, and operate to limit Aboriginal claims. Specifically, it is argued that in linking Aboriginality to the abuse of Aboriginal children, the intervention’s advocates and supporters establish a political debate about the nature and future of Aboriginality within a discursive terrain in which the authority and perspectives of Indigenous people are problematised. Aboriginality is constructed in this process as both temporally and spatially separated from settler society, and in need of coercive integration into mainstream economic and political arrangements. Aboriginality is depicted by settler advocates of intervention as an anachronism, with Aboriginal people and cultures understood as primitive and/or savage precursors to settlers who are represented as modern and civilised. As such, the communities seen as the authentic home or location of Aboriginality represent a threat to Aboriginal children as well as to settlers. These constructions function to obscure the violence of the settler order, provide justification or moral rehabilitation for the colonising project, and reassert the sovereignty of the settler state. The resolution offered by the intervention’s advocates is a performance or enactment of settler sovereignty, representing a claim over and through both the territory of Aboriginal people and the discursive terrain of nationhood.

Porohyperelastic analysis of single osteocyte using AFM and inverse FEA

Osteocytes are the mature cells and perform as mechanosensors within the bone. The mechanical property of osteocytes plays an important role to fulfill these functions. However, little researches have been done to investigate the mechanical deformation properties of single osteocytes. Atomic Force Microscopy (AFM) is a state-of-art experimental facility for high resolution imaging of tissues, cells and any surfaces as well as for probing mechanical properties of the samples both qualitatively and quantitatively. In this paper, the experimental study based on AFM is firstly used to obtain forceindentation curves of single round osteocytes. The porohyperelastic (PHE) model of a single osteocyte is then developed by using the inverse finite element analysis (FEA) to identify and extract mechanical properties from the experiment results. It has been found that the PHE model is a good candidature for biomechanics studies of osteocytes.

Queensland diabetic foot hospitalisations (2005-10) : in what state is our foot hospital problem?

Background Diabetes foot complications are a leading cause of overall avoidable hospital admissions. Since 2006, the Queensland Diabetes Clinical Network has implemented programs aimed at reducing diabetes-related hospitalisation. The aim of this retrospective observational study was to determine the incidence of diabetes foot-related hospital admissions in Queensland from 2005 to 2010. Methods Data on all primary diabetes foot-related admissions in Queensland from 2005-2010 was obtained using diabetes foot-related ICD-10-AM (hospital discharge) codes. Queensland diabetes foot-related admission incidences were calculated using general population data from the Australian Bureau of Statistics. Furthermore, diabetes foot-related sub-group admissions were analysed. Chi-squared tests were used to assess changes in admissions over time. Results Overall, 24,917 diabetes foot-related admissions occurred, resulting in the use of 260,085 bed days or 1.4% of all available Queensland hospital bed days (18,352,152). The primary reasons for these admissions were foot ulcers (49.8%), cellulitis (20.7%), peripheral vascular disease (17.8%) and osteomyelitis (3.8%). The diabetes foot-related admission incidence among the general population (per 100,000) reduced by 22% (103.0 in 2005, to 80.7 in 2010, p < 0.001); bed days decreased by 18% (1,099 to 904, p < 0.001). Conclusion Diabetes foot complications appear to be the primary reason for 1.4 out of every 100 hospital beds used in Queensland. There has been a significant reduction in the incidence of diabetes foot-related admissions in Queensland between 2005 and 2010. This decrease has coincided with a corresponding decrease in amputations and the implementation of several diabetes foot clinical programs throughout Queensland.

Flag state responsibility for maritime terrorism

Modern international shipping is largely a flag state-based system. Only the flag state has complete authority over the vessels that fly its flag, and as a result, other states’ jurisdiction over these vessels is very limited. Against this backdrop, this article examines the flag state’s responsibility for maritime terrorism, a major security issue and vulnerability in the global supply chain. It is not an exaggeration that the global community’s repeated statements regarding the illegality of terrorism have created a customary international law obligation for states to take all possible steps for the prevention of terrorism. This article argues that providing flags to suspicious entities in an obscure registration system is not compatible with this obligation.

State responsibility for maritime terrorism

Maritime terrorism is one of the main maritime security issues in the contemporary world. The threat of maritime terrorism is more apparent than ever in the post-September 11 era. Although maritime terrorism is an old issue, the disastrous events of 11 September 2001 brought this issue again onto the global agenda. This incident brought to the forefront the longstanding concerns that terrorists could severely disrupt the global maritime supply chain by using shipping containers or vessels to attack major business centres, port facilities and offshore installations. A number of international criminal law studies have been conducted to identify international legal challenges in maritime security. Some of these works have critically examined the international legal framework for maritime security and identified the lacunas in the existing system. Some of these writings have also identified that emerging maritime terrorism issues are prompting States to introduce some stringent measures. Although the international legal regime related to maritime terrorism is a well-researched area, very little research work has explored the legal issues related to State responsibility for maritime terrorism. This article argues that, although the United Nations Convention on the Law of the Sea (UNCLOS) provisions related to maritime piracy may not be applicable for some dimensions of maritime violence, different provisions of UNCLOS may relevant in identifying State responsibility for maritime terrorism.

The Australian welfare state : who benefits now?

This text outlines the links between Australian's conceptions about welfare and the redistributive outcomes of the welfare state, canvassing theoretical explanations about why many Australians develop and maintain misconceptions of the broad disyributive mechanisms of the Ayustralian welfare state and hold negative attitudes towards its social welfare element. The book is an indispensable resource for students undertaking studies in sociology, social policy, public administrion and social work.

Work and the Welfare State : Street-Level Organizations and Workfare Politics

Work and the Welfare State places street-level organizations at the analytic center of welfare state politics, policy and management. This volume offers a critical examination of efforts to change the welfare state to a workfare state by looking at on-the-ground issues in six countries: the United States, United Kingdom, Australia, Denmark, Germany and the Netherlands.

Optimal camera planning under versatile user constraints in multi-camera image processing systems

The selection of optimal camera configurations (camera locations, orientations, etc.) for multi-camera networks remains an unsolved problem. Previous approaches largely focus on proposing various objective functions to achieve different tasks. Most of them, however, do not generalize well to large scale networks. To tackle this, we propose a statistical framework of the problem as well as propose a trans-dimensional simulated annealing algorithm to effectively deal with it. We compare our approach with a state-of-the-art method based on binary integer programming (BIP) and show that our approach offers similar performance on small scale problems. However, we also demonstrate the capability of our approach in dealing with large scale problems and show that our approach produces better results than two alternative heuristics designed to deal with the scalability issue of BIP. Last, we show the versatility of our approach using a number of specific scenarios.

Semi-binary based video features for activity representation

Efficient and effective feature detection and representation is an important consideration when processing videos, and a large number of applications such as motion analysis, 3D scene understanding, tracking etc. depend on this. Amongst several feature description methods, local features are becoming increasingly popular for representing videos because of their simplicity and efficiency. While they achieve state-of-the-art performance with low computational complexity, their performance is still too limited for real world applications. Furthermore, rapid increases in the uptake of mobile devices has increased the demand for algorithms that can run with reduced memory and computational requirements. In this paper we propose a semi binary based feature detectordescriptor based on the BRISK detector, which can detect and represent videos with significantly reduced computational requirements, while achieving comparable performance to the state of the art spatio-temporal feature descriptors. First, the BRISK feature detector is applied on a frame by frame basis to detect interest points, then the detected key points are compared against consecutive frames for significant motion. Key points with significant motion are encoded with the BRISK descriptor in the spatial domain and Motion Boundary Histogram in the temporal domain. This descriptor is not only lightweight but also has lower memory requirements because of the binary nature of the BRISK descriptor, allowing the possibility of applications using hand held devices.We evaluate the combination of detectordescriptor performance in the context of action classification with a standard, popular bag-of-features with SVM framework. Experiments are carried out on two popular datasets with varying complexity and we demonstrate comparable performance with other descriptors with reduced computational complexity.

Swimmer localization from a moving camera

At the highest level of competitive sport, nearly all performances of athletes (both training and competitive) are chronicled using video. Video is then often viewed by expert coaches/analysts who then manually label important performance indicators to gauge performance. Stroke-rate and pacing are important performance measures in swimming, and these are previously digitised manually by a human. This is problematic as annotating large volumes of video can be costly, and time-consuming. Further, since it is difficult to accurately estimate the position of the swimmer at each frame, measures such as stroke rate are generally aggregated over an entire swimming lap. Vision-based techniques which can automatically, objectively and reliably track the swimmer and their location can potentially solve these issues and allow for large-scale analysis of a swimmer across many videos. However, the aquatic environment is challenging due to fluctuations in scene from splashes, reflections and because swimmers are frequently submerged at different points in a race. In this paper, we temporally segment races into distinct and sequential states, and propose a multimodal approach which employs individual detectors tuned to each race state. Our approach allows the swimmer to be located and tracked smoothly in each frame despite a diverse range of constraints. We test our approach on a video dataset compiled at the 2012 Australian Short Course Swimming Championships.