123 resultados para Moving Targets


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The progression of a tumour from one of benign and delimited growth to one that is invasive and metastatic is the major cause of poor clinical outcome in cancer patients. The invasion and metastasis of tumours is a highly complex and multistep process that requires a tumour cell to modulate its ability to adhere, degrade the surrounding extracellular matrix, migrate, proliferate at a secondary site and stimulate angiogenesis. Knowledge of the process has greatly increased and this has resulted in the identification of a number of molecules that are fundamental to the process. The involvement of these molecules has been shown to relate not only to the survival and proliferation of the tumour cell but, also to the processes of tumour cell adhesion, migration, and the tumour cells ability to degrade and escape the primary site as well as play a role in angiogenesis. These molecules may provide important therapeutic targets that represent the ability to target specific steps in the process of invasion and metastasis and provide additional therapies. The review focuses on representative key targets in each of these processes and summarises the state of play in each case.

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In this Letter a hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line is proposed. A family of spatially varying slip lengths in the Navier slip law recovers the results of past formulations for slip in continuum theories and molecular dynamics simulations and is consistent with well-established experimental observations of complete wetting. This formulation gives a general approach for continuum hydrodynamic theories. New fluid flow behaviors are also predicted yet to be seen in experiment. © 2013 American Physical Society.

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Realizing the promise of molecularly targeted inhibitors for cancer therapy will require a new level of knowledge about how a drug target is wired into the control circuitry of a complex cellular network. Here we review general homeostatic principles of cellular networks that enable the cell to be resilient in the face of molecular perturbations, while at the same time being sensitive to subtle input signals. Insights into such mechanisms may facilitate the development of combination therapies that take advantage of the cellular control circuitry, with the aim of achieving higher efficacy at a lower drug dosage and with a reduced probability of drug-resistance development.

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Like the UK, Australia has a number of school nursing models and programmes. The School Based Youth Health Nurse Program (SBYHNP) is a new and unique model of school nursing in Queensland, Australia. The SBYHNP represents a philosophical and structural shift from traditional school nursing programmes. The purpose of this qualitative case study is to explore the reasons School Based Youth Health Nurses (SBYHN) leave school nursing. Sixteen in-depth interviews were conducted with participants who practiced as SBYHN and left the SBYHNP. This case study reveals six themes: The politics’: Navigating the organisational divide, 'Unconditional positive regard’: Surviving without team cohesion, 'Absolutely exhausted’: Maintaining physical and emotional strength, ‘Definitely geographical’: Managing the tyranny of time and distance, ‘If things fell into place’: Thinking about what could have been, and ‘A stepping stone’: Moving on to the next nursing position. This case study suggests nurses considering school nursing as a specialty should seek opportunity to understand this complex role, ensure realistic expectations and ndertake relevant qualifications. This approach may secure the investment made by nurses and schools and create demand for a highly sort after position.

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Oncogenic mutations in BRAF are common in melanoma and drive constitutive activation of the MEK/ERK pathway. To elucidate the transcriptional events downstream of V600EBRAF/MEK signalling we performed gene expression profiling of A375 melanoma cells treated with potent and selective inhibitors of V600EBRAF and MEK (PLX4720 and PD184352 respectively). Using a stringent Bayesian approach, we identified 69 transcripts that appear to be direct transcriptional targets of this pathway and whose expression changed after 6 h of pathway inhibition. We also identified several additional genes whose expression changed after 24 h of pathway inhibition and which are likely to be indirect transcriptional targets of the pathway. Several of these were confirmed by demonstrating their expression to be similarly regulated when BRAF was depleted using RNA interference, and by using qRT-PCR in other BRAF mutated melanoma lines. Many of these genes are transcription factors and feedback inhibitors of the ERK pathway and are also regulated by MEK signalling in NRAS mutant cells. This study provides a basis for understanding the molecular processes that are regulated by V600EBRAF/MEK signalling in melanoma cells.

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As a Lecturer of Animation History and 3D Computer Animator, I received a copy of Moving Innovation: A History of Computer Animation by Tom Sito with an element of anticipation in the hope that this text would clarify the complex evolution of Computer Graphics (CG). Tom Sito did not disappoint, as this text weaves together the multiple development streams and convergent technologies and techniques throughout history that would ultimately result in modern CG. Universities now have students who have never known a world without computer animation and many students are younger than the first 3D CG animated feature film, Toy Story (1996); this text is ideal for teaching computer animation history and, as I would argue, it also provides a model for engaging young students in the study of animation history in general. This is because Sito places the development of computer animation within the context of its pre-digital ancestry and throughout the text he continues to link the discussion to the broader history of animation, its pioneers, technologies and techniques...

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"Despite the 10 months of grieving for those lost in Queensland’s January floods, new evidence produced during the coronial inquest into the 22 deaths and three disappearances has revealed new shocks for the bereaved families. Brisbane Coroner’s Court yesterday was introduced to a series of high-tech Google Earth animations backed by funereal music, explaining the scope of the unfolding tragedy, which swept away husbands, wives, children and grandparents in less than three hours on the afternoon of January 10 this year. The court was also told of the extensive search for human remains, of 131 kilometres of creeks and rivers from Spring Bluff to Brisbane and hundreds of dams that were searched three times by police divers, 250 army personnel and 200 police."

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Silica coated Ag nanoparticles with defined surface plasmon resonances are used to selectively detect and analyze protein cofactors in solution and on interfaces via surface enhanced resonance Raman spectroscopy. The silica coating has a surprisingly small effect on optical amplification but minimizes unwanted interactions between the protein and the nanoparticle.

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Background and Purpose: - This paper focuses on the learning culture within the high performance levels of rowing. In doing so, we explore the case of an individual’s learning as he moves across athletic, coaching and administrative functions. This exploration draws on a cultural learning framework and complementary theorisings related to reflexivity. Method - This study makes use of an intellectually, morally and collaboratively challenging approach whereby one member of the research team was also the sole participant of this study. The participant’s careers as a high performance athlete, coach and administrator, coupled with his experience in conducting empirical research presented a rare opportunity to engage in collaborative research (involving degrees of insider and outsider status for each of the research team). We acknowledge that others have looked to combine roles of coach / athlete / administrator with that of researcher however few (if any) have attempted to combine them all in one project. Moreover, coupled with the approach to reflexivity adopted in this study and the authorship contributions we consider this scholarly direction uncommon. Data were comprised of recorded research conversations, a subsequently constructed learning narrative, reflections on the narrative, a stimulated reflective piece from the participant, and a final (re)construction of the participant’s story. Accordingly, data were integrated through an iterative process of thematic analysis. Results - The cultural (i.e., the ways things get done) and structural (e.g., the rules and regulations) properties of high performance rowing were found to shape both the opportunities to be present (e.g., secure a place in the crew) and to learn (e.g., learn the skills required to perform at an Olympic level). However, the individual’s personal properties were brought to bear on re-shaping the constraints such that many limitations could be overcome. In keeping with the theory of learning cultures, the culture of rowing was found to position individuals (a coxswain in this case) differentially. In a similar manner, a range of structural features was found to be important in shaping the cultural and personal elements in performance contexts. For example, the ‘field of play’ was found to be important as a structural feature (i.e., inability of coach to communicate with athletes) in shaping the cultural and personal elements of learning in competition (e.g., positioning the coxswain as an in-boat coach and trusted crewmate). Finally, the cultural and structural elements in rowing appeared to be activated by the participant’s personal elements, most notably his orientation towards quality performance. Conclusion - The participant in this study was found to be driven by the project that he cares about most and at each turn he has bent his understanding of his sport back on itself to see if he can find opportunities to learn and subsequently explore ways to improve performance. The story here emphasises the importance of learner agency, and this is an aspect that has often been missing in recent theorising about learning. In this study, we find an agent using his ‘personal emergent powers to activate the resources in the culture and structure of his sport in an attempt to improve performance. We conclude from this account that this particular high performance rowing culture is one that provided support but nonetheless encouraged those involved, to ‘figure things out’ for themselves – be it as athletes, coaches and/or administrators.

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Currently, across dance studies, choreographies are usually discussed as representational of the choreographer, with little attention focused on the dancers who also bring the work into being. As well as devaluing the contribution that the dancer makes to the choreographic process, the dancer’s elision from mainstream discourse deprives the art form of a rich source of insight into the incorporating practices of dance. This practice-based research offers a new perspective on choreographic process through the experiential viewpoint of the participating dancer. It involves encounters with contemporary choreographers Rosemary Butcher (UK), John Jasperse (US), Jodi Melnick (US) and Liz Roche (Ire). Utilizing a mixed-mode research structure, it covers the creative process and performance of three solo dance pieces in Dublin in 2008, as well as an especially composed movement treatise, all of which are documented on the attached DVD. The main hypothesis presented is that the dancer possesses a moving identity which is a composite of past dance experience, anatomical structures and conditioned human movement. This is supported by explorations into critical theory on embodiment, including Pierre Bourdieu’s concept of ‘the habitus’. The moving identity is identified as accumulative, altering through encounters with new choreographic movement patterns in independent contemporary dance practice. The interior space of the dancer’s embodied experience is made explicit in chapter 3, through four discussions that outline the dancer’s creative labour in producing each choreographic work. Through adopting a postmodern critical perspective on human subjectivity, supported by Gilles Deleuze, Félix Guattari and Alain Badiou, among others, the thesis addresses the inherent challenges which face independent contemporary dancers within their multiple embodiments as they move between different choreographic processes. In identifying an emergent paradigmatic shift in the role of dancer within dance- making practices, this research forges a new direction that invites further dancer-led initiatives in practice-based research.

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Background Road safety targets are widely used and provide a basis for evaluating progress in road safety outcomes against a quantified goal. In Australia, a reduction in fatalities from road traffic crashes (RTCs) is a public policy objective: a national target of no more than 5.6 fatalities per 100,000 population by 2010 was set in 2001. The purpose of this paper is to examine the progress Australia and its states and territories have made in reducing RTC fatalities, and to estimate when the 2010 target may be reached by the jurisdictions. Methods Following a descriptive analysis, univariate time-series models estimate past trends in fatality rates over recent decades. Data for differing time periods are analysed and different trend specifications estimated. Preferred models were selected on the basis of statistical criteria and the period covered by the data. The results of preferred regressions are used to determine out-of-sample forecasts of when the national target may be attained by the jurisdictions. Though there are limitations with the time series approach used, inadequate data precluded the estimation of a full causal/structural model. Results Statistically significant reductions in fatality rates since 1971 were found for all jurisdictions with the national rate decreasing on average, 3% per year since 1992. However the gains have varied across time and space, with percent changes in fatality rates ranging from an 8% increase in New South Wales 1972-1981 to a 46% decrease in Queensland 1982-1991. Based on an estimate of past trends, it is possible that the target set for 2010 may not be reached nationally, until 2016. Unsurprisingly, the analysis indicated a range of outcomes for the respective state/territory jurisdictions though these results should be interpreted with caution due to different assumptions and length of data. Conclusions Results indicate that while Australia has been successful over recent decades in reducing RTC mortality, an important gap between aspirations and achievements remains. Moreover, unless there are fairly radical ("trend-breaking") changes in the factors that affect the incidence of RTC fatalities, deaths from RTCs are likely to remain above the national target in some areas of Australia, for years to come.

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Human half-lives of PentaBDE congeners have been estimated from the decline in serum concentrations measured over a 6-12 month period for a population of exchange students moving from North America to Australia. Australian serum PBDE concentrations are typically between 5 -10 times lower than in North America and we can therefore hypothesize that if the biological half-life is sufficiently short we would observe a decline in serum concentration with length of residence in Australia. Thirty students were recruited over a period of 3 years from whom serum were archived every 2 months during their stay in Australia. Australian residents (n=22) were also sampled longitudinally to estimate general population background levels. All serum samples were analyzed by gas chromatography high resolution mass spectrometry. Key findings confirmed that BDE-47 concentrations in the Australians (median 2.3;