846 resultados para resistant data


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Members of the World Trade Organisation (WTO) are obliged to implement the Agreement on Trade-related Intellectual Property Rights 1994 (TRIPS) which establishes minimum standards for the protection and enforcement of intellectual property rights. Almost two decades after TRIPS was adopted at the conclusion of the Uruguay Round of trade negotiations, it is widely accepted that intellectual property systems in developing and least-developed countries must be consistent with, and serve, their development needs and objectives. In adopting the Development Agenda in 2007, the World Intellectual Property Organisation (WIPO) emphasised the importance to developing and least-developed countries of being able to obtain access to knowledge and technology and to participate in collaborations and exchanges with research and scientific institutions in other countries. Access to knowledge, information and technology is crucial if creativity and innovation is to be fostered in developing and least-developed countries. It is particularly important that developing and least-developed countries give effect to their TRIPS obligations by implementing intellectual property systems and adopting intellectual property management practices that enable them to benefit from knowledge flows and support their engagement in international research and science collaborations. However, developing and least-developed countries did not participate in the deliberations leading to the adoption in 2004 by Organisation for Economic Co-operation and Development (OECD) member countries of the Ministerial Declaration on Access to Research Data from Public Funding, nor have they formulated policies on access to publicly funded research outputs such as those developed by the National Institutes of Health in the United States, the United Kingdom Research Councils or the Australian National Health and Medical Research Council. These issues are considered from the viewpoint of Malaysia, a developing country whose economy has grown strongly in recent years. Lacking an established policy covering access to the outputs of publicly funded research, data sharing and licensing practices continue to be fragmented. Obtaining access to research data requires arrangements to be negotiated with individual data owners and custodians. Given the potential for restrictions on access to impact negatively on scientific progress and development in Malaysia, measures are required to ensure that access to knowledge and research results is facilitated. This paper proposes a policy framework for Malaysia‘s public research universities that recognises intellectual property rights while enabling the open access to research data that is essential for innovation and development. It also considers how intellectual property rights in research data can be managed in order to give effect to the policy‘s open access objectives.

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Buildings are key mediators between human activity and the environment around them, but details of energy usage and activity in buildings is often poorly communicated and understood. ECOS is an Eco-Visualization project that aims to contextualize the energy generation and consumption of a green building in a variety of different climates. The ECOS project is being developed for a large public interactive space installed in the new Science and Engineering Centre of the Queensland University of Technology that is dedicated to delivering interactive science education content to the public. This paper focuses on how design can develop ICT solutions from large data sets to create meaningful engagement with environmental data.

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Key decisions at the collection, pre-processing, transformation, mining and interpretation phase of any knowledge discovery from database (KDD) process depend heavily on assumptions and theorectical perspectives relating to the type of task to be performed and characteristics of data sourced. In this article, we compare and contrast theoretical perspectives and assumptions taken in data mining exercises in the legal domain with those adopted in data mining in TCM and allopathic medicine. The juxtaposition results in insights for the application of KDD for Traditional Chinese Medicine.

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Citizen Science projects are initiatives in which members of the general public participate in scientific research projects and perform or manage research-related tasks such as data collection and/or data annotation. Citizen Science is technologically possible and scientifically significant. However, as the gathered information is from the crowd, the data quality is always hard to manage. There are many ways to manage data quality, and reputation management is one of the common approaches. In recent year, many research teams have deployed many audio or image sensors in natural environment in order to monitor the status of animals or plants. The collected data will be analysed by ecologists. However, as the amount of collected data is exceedingly huge and the number of ecologists is very limited, it is impossible for scientists to manually analyse all these data. The functions of existing automated tools to process the data are still very limited and the results are still not very accurate. Therefore, researchers have turned to recruiting general citizens who are interested in helping scientific research to do the pre-processing tasks such as species tagging. Although research teams can save time and money by recruiting general citizens to volunteer their time and skills to help data analysis, the reliability of contributed data varies a lot. Therefore, this research aims to investigate techniques to enhance the reliability of data contributed by general citizens in scientific research projects especially for acoustic sensing projects. In particular, we aim to investigate how to use reputation management to enhance data reliability. Reputation systems have been used to solve the uncertainty and improve data quality in many marketing and E-Commerce domains. The commercial organizations which have chosen to embrace the reputation management and implement the technology have gained many benefits. Data quality issues are significant to the domain of Citizen Science due to the quantity and diversity of people and devices involved. However, research on reputation management in this area is relatively new. We therefore start our investigation by examining existing reputation systems in different domains. Then we design novel reputation management approaches for Citizen Science projects to categorise participants and data. We have investigated some critical elements which may influence data reliability in Citizen Science projects. These elements include personal information such as location and education and performance information such as the ability to recognise certain bird calls. The designed reputation framework is evaluated by a series of experiments involving many participants for collecting and interpreting data, in particular, environmental acoustic data. Our research in exploring the advantages of reputation management in Citizen Science (or crowdsourcing in general) will help increase awareness among organizations that are unacquainted with its potential benefits.

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Health complaint statistics are important for identifying problems and bringing about improvements to health care provided by health service providers and to the wider health care system. This paper overviews complaints handling by the eight Australian state and territory health complaint entities, based on an analysis of data from their annual reports. The analysis shows considerable variation between jurisdictions in the ways complaint data are defined, collected and recorded. Complaints from the public are an important accountability mechanism and open a window on service quality. The lack of a national approach leads to fragmentation of complaint data and a lost opportunity to use national data to assist policy development and identify the main areas causing consumers to complain. We need a national approach to complaints data collection in order to better respond to patients’ concerns.

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An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.

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Expression of caveolin-1 is up-regulated in prostate cancer metastasis and is associated with aggressive recurrence of the disease. Intriguingly, caveolin-1 is also secreted from prostate cancer cell lines and has been identified in secreted prostasomes. Caveolin-1 is the major structural component of the plasma membrane invaginations called caveolae. Co-expression of the coat protein Polymerase I and transcript release factor (PTRF) is required for caveolae formation. We recently found that expression of caveolin-1 in the aggressive prostate cancer cell line PC-3 is not accompanied by PTRF, leading to noncaveolar caveolin-1 lipid rafts. Moreover, ectopic expression of PTRF in PC-3 cells sequesters caveolin-1 into caveolae. Here we quantitatively analyzed the effect of PTRF expression on the PC-3 proteome using stable isotope labeling by amino acids in culture and subcellular proteomics. We show that PTRF reduced the secretion of a subset of proteins including secreted proteases, cytokines, and growth regulatory proteins, partly via a reduction in prostasome secretion. To determine the cellular mechanism accounting for the observed reduction in secreted proteins we analyzed total membrane and the detergent-resistant membrane fractions. Our data show that PTRF expression selectively impaired the recruitment of actin cytoskeletal proteins to the detergent-resistant membrane, which correlated with altered cholesterol distribution in PC-3 cells expressing PTRF. Consistent with this, modulating cellular cholesterol altered the actin cytoskeleton and protein secretion in PC-3 cells. Intriguingly, several proteins that function in ER to Golgi trafficking were reduced by PTRF expression. Taken together, these results suggest that the noncaveolar caveolin-1 found in prostate cancer cells generates a lipid raft microenvironment that accentuates secretion pathways, possibly at the step of ER sorting/exit. Importantly, these effects could be modulated by PTRF expression.

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Mebendazole (MBZ) was identified as a promising therapeutic on the basis of its ability to induce apoptosis in melanoma cell lines through a B-cell lymphoma 2 (BCL2)-dependent mechanism. We now show that in a human xenograft melanoma model, oral MBZ is as effective as the current standard of care temozolomide in reducing tumor growth. Inhibition of melanoma growth in vivo is accompanied by phosphorylation of BCL2 and decreased levels of X-linked inhibitor of apoptosis (XIAP). Reduced expression of XIAP on treatment with MBZ is partially mediated by its proteasomal degradation. Furthermore, exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating XIAP's inhibition on apoptosis. XIAP expression on exposure to MBZ is indicative of sensitivity to MBZ as MBZ-resistant cells do not show reduced levels of XIAP after treatment. Resistance to MBZ can be reversed partially by siRNA knockdown of cellular levels of XIAP. Our data indicate that MBZ is a promising antimelanoma agent on the basis of its effects on key antiapoptotic proteins.

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BACKGROUND: Melanoma is the most lethal form of skin cancer, but recent advances in molecularly targeted agents against the Ras/Raf/MAPK pathway demonstrate promise as effective therapies. Despite these advances, resistance remains an issue, as illustrated recently by the clinical experience with vemurafenib. Such acquired resistance appears to be the result of parallel pathway activation, such as PI3K, to overcome single-agent inhibition. In this report, we describe the cytotoxicity and anti-tumour activity of the novel MEK inhibitor, E6201, in a broad panel of melanoma cell lines (n = 31) of known mutational profile in vitro and in vivo. We further test the effectiveness of combining E6201 with an inhibitor of PI3K (LY294002) in overcoming resistance in these cell lines. RESULTS: The majority of melanoma cell lines were either sensitive (IC50 < 500 nM, 24/31) or hypersensitive (IC50 < 100 nM, 18/31) to E6201. This sensitivity correlated with wildtype PTEN and mutant BRAF status, whereas mutant RAS and PI3K pathway activation were associated with resistance. Although MEK inhibitors predominantly exert a cytostatic effect, E6201 elicited a potent cytocidal effect on most of the sensitive lines studied, as evidenced by Annexin positivity and cell death ELISA. Conversely, E6201 did not induce cell death in the two resistant melanoma cell lines tested. E6201 inhibited xenograft tumour growth in all four melanoma cell lines studied to varying degrees, but a more pronounced anti-tumour effect was observed for cell lines that previously demonstrated a cytocidal response in vitro. In vitro combination studies of E6201 and LY294002 showed synergism in all six melanoma cell lines tested, as defined by a mean combination index < 1. CONCLUSIONS: Our data demonstrate that E6201 elicits a predominantly cytocidal effect in vitro and in vivo in melanoma cells of diverse mutational background. Resistance to E6201 was associated with disruption of PTEN and activation of downstream PI3K signalling. In keeping with these data we demonstrate that co-inhibition of MAPK and PI3K is effective in overcoming resistance inherent in melanoma.

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In this article, we report transgene-derived resistance in maize to the severe pathogen maize streak virus (MSV). The mutated MSV replication-associated protein gene that was used to transform maize showed stable expression to the fourth generation. Transgenic T 2 and T 3 plants displayed a significant delay in symptom development, a decrease in symptom severity and higher survival rates than non-transgenic plants after MSV challenge, as did a transgenic hybrid made by crossing T 2 Hi-II with the widely grown, commercial, highly MSV-susceptible, white maize genotype WM3. To the best of our knowledge, this is the first maize to be developed with transgenic MSV resistance and the first all-African-produced genetically modified crop plant. © 2007 The Authors.

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Background: National physical activity data suggest that there is a considerable difference in physical activity levels of US and Australian adults. Although different surveys (Active Australia and BRFSS) are used, the questions are similar. Different protocols, however, are used to estimate “activity” from the data collected. The primary aim of this study was to assess whether the 2 approaches to the management of PA data could explain some of the difference in prevalence estimates derived from the two national surveys. Methods: Secondary data analysis of the most recent AA survey (N = 2987). Results: 15% of the sample was defined as “active” using Australian criteria but as “inactive” using the BRFSS protocol, even though weekly energy expenditure was commensurate with meeting current guidelines. Younger respondents (age < 45 y) were more likely to be “misclassified” using the BRFSS criteria. Conclusions: The prevalence of activity in Australia and the US appears to be more similar than we had previously thought.

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Client owners usually need an estimate or forecast of their likely building costs in advance of detailed design in order to confirm the financial feasibility of their projects. Because of their timing in the project life cycle, these early stage forecasts are characterized by the minimal amount of information available concerning the new (target) project to the point that often only its size and type are known. One approach is to use the mean contract sum of a sample, or base group, of previous projects of a similar type and size to the project for which the estimate is needed. Bernoulli’s law of large numbers implies that this base group should be as large as possible. However, increasing the size of the base group inevitably involves including projects that are less and less similar to the target project. Deciding on the optimal number of base group projects is known as the homogeneity or pooling problem. A method of solving the homogeneity problem is described involving the use of closed form equations to compare three different sampling arrangements of previous projects for their simulated forecasting ability by a cross-validation method, where a series of targets are extracted, with replacement, from the groups and compared with the mean value of the projects in the base groups. The procedure is then demonstrated with 450 Hong Kong projects (with different project types: Residential, Commercial centre, Car parking, Social community centre, School, Office, Hotel, Industrial, University and Hospital) clustered into base groups according to their type and size.

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Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

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The selection of appropriate analogue materials is a central consideration in the design of realistic physical models. We investigate the rheology of highly-filled silicone polymers in order to find materials with a power-law strain-rate softening rheology suitable for modelling rock deformation by dislocation creep and report the rheological properties of the materials as functions of the filler content. The mixtures exhibit strain-rate softening behaviour but with increasing amounts of filler become strain-dependent. For the strain-independent viscous materials, flow laws are presented while for strain-dependent materials the relative importance of strain and strain rate softening/hardening is reported. If the stress or strain rate is above a threshold value some highly-filled silicone polymers may be considered linear visco-elastic (strain independent) and power-law strain-rate softening. The power-law exponent can be raised from 1 to ~3 by using mixtures of high-viscosity silicone and plasticine. However, the need for high shear strain rates to obtain the power-law rheology imposes some restrictions on the usage of such materials for geodynamic modelling. Two simple shear experiments are presented that use Newtonian and power-law strain-rate softening materials. The results demonstrate how materials with power-law rheology result in better strain localization in analogue experiments.