248 resultados para Regulatory Elements, Transcriptional
Resumo:
Experimental and theoretical studies have shown the importance of stochastic processes in genetic regulatory networks and cellular processes. Cellular networks and genetic circuits often involve small numbers of key proteins such as transcriptional factors and signaling proteins. In recent years stochastic models have been used successfully for studying noise in biological pathways, and stochastic modelling of biological systems has become a very important research field in computational biology. One of the challenge problems in this field is the reduction of the huge computing time in stochastic simulations. Based on the system of the mitogen-activated protein kinase cascade that is activated by epidermal growth factor, this work give a parallel implementation by using OpenMP and parallelism across the simulation. Special attention is paid to the independence of the generated random numbers in parallel computing, that is a key criterion for the success of stochastic simulations. Numerical results indicate that parallel computers can be used as an efficient tool for simulating the dynamics of large-scale genetic regulatory networks and cellular processes
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Recent studies have shown that small genetic regulatory networks (GRNs) can be evolved in silico displaying certain dynamics in the underlying mathematical model. It is expected that evolutionary approaches can help to gain a better understanding of biological design principles and assist in the engineering of genetic networks. To take the stochastic nature of GRNs into account, our evolutionary approach models GRNs as biochemical reaction networks based on simple enzyme kinetics and simulates them by using Gillespie’s stochastic simulation algorithm (SSA). We have already demonstrated the relevance of considering intrinsic stochasticity by evolving GRNs that show oscillatory dynamics in the SSA but not in the ODE regime. Here, we present and discuss first results in the evolution of GRNs performing as stochastic switches.
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Video games have shown great potential as tools that both engage and motivate players to achieve tasks and build communities in fantasy worlds. We propose that the application of game elements to real world activities can aid in delivering contextual information in interesting ways and help young people to engage in everyday events. Our research will explore how we can unite utility and fun to enhance information delivery, encourage participation, build communities and engage users with utilitarian events situated in the real world. This research aims to identify key game elements that work effectively to engage young digital natives, and provide guidelines to influence the design of interactions and interfaces for event applications in the future. This research will primarily contribute to areas of user experience and pervasive gaming.
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The field of bereavement and grief has been expanding to recognise the potential for growth following the loss of a loved one. This study sought to examine the effect of the relationship to the deceased and perceptions of the severity of the trauma on dimensions of posttraumatic growth. Participants were 146 people who had lost either: a) a first degree relative, b) a second degree relative, or c) a non-related friend. Results demonstrated that both severity and the relationship to the bereaved differentiate posttraumatic growth outcomes. For example, participants who had lost a first degree relative reported higher levels of growth than those who had lost a second degree relative. Consistent with previous research in general trauma populations, the more severe the loss was rated, the higher the levels of growth. Implications for practice are discussed.
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This paper considers issues of methodological innovation in communication, media and cultural studies, that arise out of the extent to which we now live in a media environment characterised by an digital media abundance, the convergence of media platforms, content and services, and the globalisation of media content through ubiquitous computing and high-speed broadband networks. These developments have also entailed a shift in the producer-consumer relationships that characterised the 20th century mass communications paradigm, with the rapid proliferation of user-created content, accelerated innovation, the growing empowerment of media users themselves, and the blurring of distinctions between public and private, as well as age-based distinctions in terms of what media can be accessed by whom and for what purpose. It considers these issues through a case study of the Australian Law Reform Commission's National Classification Scheme Review.
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Molluscan larval ontogeny is a highly conserved process comprising three principal developmental stages. A characteristic unique to each of these stages is shell design, termed prodissoconch I, prodissoconch II and dissoconch. These shells vary in morphology, mineralogy and microstructure. The discrete temporal transitions in shell biomineralization between these larval stages are utilized in this study to investigate transcriptional involvement in several distinct biomineralization events. Scanning electron microscopy and X-ray diffraction analysis of P. maxima larvae and juveniles collected throughout post-embryonic ontogenesis, document the mineralogy and microstructure of each shelled stage as well as establishing a timeline for transitions in biomineralization. P. maxima larval samples most representative of these biomineralization distinctions and transitions were analyzed for differential gene expression on the microarray platform PmaxArray 1.0. A number of transcripts are reported as differentially expressed in correlation to the mineralization events of P. maxima larval ontogeny. Some of those isolated are known shell matrix genes while others are novel; these are discussed in relation to potential shell formation roles. This interdisciplinary investigation has linked the shell developments of P. maxima larval ontogeny with corresponding gene expression profiles, furthering the elucidation of shell biomineralization.
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The Queensland Building Services Authority (QBSA) regulates the construction industry in Queensland, Australia, with licensing requirements creating differential financial reporting obligations, depending on firm size. Economic theories of regulation and behaviour provide a framework for investigating effects of the financial constraints and financial reporting requirements imposed by QBSA licensing. Data are analysed for all small and medium construction entities operating in Queensland between 2001 and 2006. Findings suggesting that construction licensees are categorizing themselves as smaller to avoid the more onerous and costly financial reporting of higher licensee categories are consistent with US findings from the 2002 Sarbanes-Oxley (SOX) regulation which created incentives for small firms to stay small to avoid the costs of compliance with more onerous financial reporting requirements. Such behaviour can have the undesirable economic consequences of adversely affecting employment, investment, wealth creation and financial stability. Insights and implications from the analysed QBSA processes are important for future policy reform and design, and useful to be considered where similar regulatory approaches are planned.
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Purpose – The purpose of this paper is to jointly assess the impact of regulatory reform for corporate fundraising in Australia (CLERP Act 1999) and the relaxation of ASX admission rules in 1999, on the accuracy of management earnings forecasts in initial public offer (IPO) prospectuses. The relaxation of ASX listing rules permitted a new category of new economy firms (commitments test entities (CTEs))to list without a prior history of profitability, while the CLERP Act (introduced in 2000) was accompanied by tighter disclosure obligations and stronger enforcement action by the corporate regulator (ASIC). Design/methodology/approach – All IPO earnings forecasts in prospectuses lodged between 1998 and 2003 are examined to assess the pre- and post-CLERP Act impact. Based on active ASIC enforcement action in the post-reform period, IPO firms are hypothesised to provide more accurate forecasts, particularly CTE firms, which are less likely to have a reasonable basis for forecasting. Research models are developed to empirically test the impact of the reforms on CTE and non-CTE IPO firms. Findings – The new regulatory environment has had a positive impact on management forecasting behaviour. In the post-CLERP Act period, the accuracy of prospectus forecasts and their revisions significantly improved and, as expected, the results are primarily driven by CTE firms. However, the majority of prospectus forecasts continue to be materially inaccurate. Originality/value – The results highlight the need to control for both the changing nature of listed firms and the level of enforcement action when examining responses to regulatory changes to corporate fundraising activities.
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The compressed gas industry and government agencies worldwide utilize "adiabatic compression" testing for qualifying high-pressure valves, regulators, and other related flow control equipment for gaseous oxygen service. This test methodology is known by various terms including adiabatic compression testing, gaseous fluid impact testing, pneumatic impact testing, and BAM testing as the most common terms. The test methodology will be described in greater detail throughout this document but in summary it consists of pressurizing a test article (valve, regulator, etc.) with gaseous oxygen within 15 to 20 milliseconds (ms). Because the driven gas1 and the driving gas2 are rapidly compressed to the final test pressure at the inlet of the test article, they are rapidly heated by the sudden increase in pressure to sufficient temperatures (thermal energies) to sometimes result in ignition of the nonmetallic materials (seals and seats) used within the test article. In general, the more rapid the compression process the more "adiabatic" the pressure surge is presumed to be and the more like an isentropic process the pressure surge has been argued to simulate. Generally speaking, adiabatic compression is widely considered the most efficient ignition mechanism for directly kindling a nonmetallic material in gaseous oxygen and has been implicated in many fire investigations. Because of the ease of ignition of many nonmetallic materials by this heating mechanism, many industry standards prescribe this testing. However, the results between various laboratories conducting the testing have not always been consistent. Research into the test method indicated that the thermal profile achieved (i.e., temperature/time history of the gas) during adiabatic compression testing as required by the prevailing industry standards has not been fully modeled or empirically verified, although attempts have been made. This research evaluated the following questions: 1) Can the rapid compression process required by the industry standards be thermodynamically and fluid dynamically modeled so that predictions of the thermal profiles be made, 2) Can the thermal profiles produced by the rapid compression process be measured in order to validate the thermodynamic and fluid dynamic models; and, estimate the severity of the test, and, 3) Can controlling parameters be recommended so that new guidelines may be established for the industry standards to resolve inconsistencies between various test laboratories conducting tests according to the present standards?
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Eukaryotic cell cycle progression is mediated by phosphorylation of protein substrates by cyclin-dependent kinases (CDKs). A critical substrate of CDKs is the product of the retinoblastoma tumor suppressor gene, pRb, which inhibits G1-S phase cell cycle progression by binding and repressing E2F transcription factors. CDK-mediated phosphorylation of pRb alleviates this inhibitory effect to promote G1-S phase cell cycle progression. pRb represses transcription by binding to the E2F transactivation domain and recruiting the mSin3·histone deacetylase (HDAC) transcriptional repressor complex via the retinoblastoma-binding protein 1 (RBP1). RBP1 binds to the pocket region of pRb via an LXCXE motif and to the SAP30 subunit of the mSin3·HDAC complex and, thus, acts as a bridging protein in this multisubunit complex. In the present study we identified RBP1 as a novel CDK substrate. RBP1 is phosphorylated by CDK2 on serines 864 and 1007, which are N- and C-terminal to the LXCXE motif, respectively. CDK2-mediated phosphorylation of RBP1 or pRb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation. Consistent with these findings, RBP1 phosphorylation is increased during progression from G 1 into S-phase, with a concurrent decrease in its association with pRb in MCF-7 breast cancer cells. These studies provide new mechanistic insights into CDK-mediated regulation of the pRb tumor suppressor during cell cycle progression, demonstrating that CDK-mediated phosphorylation of both RBP1 and pRb induces their dissociation to mediate release of the mSin3·HDAC transcriptional repressor complex from pRb to alleviate transcriptional repression of E2F.
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As the international community struggles to find a cost-effective solution to mitigate climate change and reduce greenhouse gas emissions, carbon capture and storage (CCS) has emerged as a project mechanism with the potential to assist in transitioning society towards its low carbon future. Being a politically attractive option, legal regimes to promote and approve CCS have proceeded at an accelerated pace in multiple jurisdictions including the European Union and Australia. This acceleration and emphasis on the swift commercial deployment of CCS projects has left the legal community in the undesirable position of having to advise on the strengths and weaknesses of the key features of these regimes once they have been passed and become operational. This is an area where environmental law principles are tested to their very limit. On the one hand, implementation of this new technology should proceed in a precautionary manner to avoid adverse impacts on the atmosphere, local community and broader environment. On the other hand, excessive regulatory restrictions will stifle innovation and act as a barrier to the swift deployment of CCS projects around the world. Finding the balance between precaution and innovation is no easy feat. This is an area where lawyers, academics, regulators and industry representatives can benefit from the sharing of collective experiences, both positive and negative, across the jurisdictions. This exemplary book appears to have been collated with this philosophy in mind and provides an insightful addition to the global dialogue on establishing effective national and international regimes for the implementation of CCS projects...
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Climate change presents as the archetypal environmental problem with short-term economic self-interest operating to the detriment of the long-term sustainability of our society. The scientific reports of the Intergovernmental Panel on Climate Change strongly assert that the stabilisation of emissions in the atmosphere, to avoid the adverse impacts of climate change, requires significant and rapid reductions in ‘business as usual’ global greenhouse gas emissions. The sheer magnitude of emissions reductions required, within this urgent timeframe, will necessitate an unprecedented level of international, multi-national and intra-national cooperation and will challenge conventional approaches to the creation and implementation of international and domestic legal regimes. To meet this challenge, existing international, national and local legal systems must harmoniously implement a strong international climate change regime through a portfolio of traditional and innovative legal mechanisms that swiftly transform current behavioural practices in emitting greenhouse gases. These include the imposition of strict duties to reduce emissions through the establishment of strong command and control regulation (the regulatory approach); mechanisms for the creation and distribution of liabilities for greenhouse gas emissions and climaterelated harm (the liability approach) and the use of innovative regulatory tools in the form of the carbon trading scheme (the market approach). The legal relations between these various regulatory, liability and market approaches must be managed to achieve a consistent, compatible and optimally effective legal regime to respond to the threat of climate change. The purpose of this thesis is to analyse and evaluate the emerging legal rules and frameworks, both international and Australian, required for the effective regulation of greenhouse gas emissions to address climate change in the context of the urgent and deep emissions reductions required to minimise the adverse impacts of climate change. In doing so, this thesis will examine critically the existing and potential role of law in effectively responding to climate change and will provide recommendations on the necessary reforms to achieve a more effective legal response to this global phenomenon in the future.
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This article recognises the potential importance of Islamic finance products in Australia, along with the current regulatory impediments preventing Australia from becoming a leader in the Asia-Pacific Islamic finance market. Taking into account the potential importance of, and impediments to, Islamic finance, this article highlights, through the historical development and contemporary state of Islamic finance, its economic, social and political benefits to Australia. Once a case for embracing Islamic finance is made, the main current regulatory impediments to Australia becoming a key player in the Islamic finance market within the Asia-Pacific region are highlighted. This article then argues that, rather than requiring any separate regulatory regime, the current regulatory impediments may be overcome through amendments to existing laws to ensure parity of treatment in Australia between the Islamic finance market and the conventional finance market. The Australian income tax regime is utilised as a case study demonstrate how parity of treatment could be achieved via amendment by taking two frequent and separate Islamic finance transactions. This article concludes that the economic, social and political benefits potentially warrant Australia embracing Islamic finance and that, with the right regulatory measures, Australia could lay the foundation to become a leader in the Asia-Pacific Islamic finance market.
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With increasing recognition of the international market in health professionals and the impact of globalism on regulation, the governance of the health workforce is moving towards greater public engagement and increased transparency. This book discusses the challenges posed by these processes, such as improved access to health services and how structures can be reformed so that good practice is upheld and quality of service and patient safety are ensured.