987 resultados para biomarker discovery


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In this paper we discuss our current efforts to develop and implement an exploratory, discovery mode assessment item into the total learning and assessment profile for a target group of about 100 second level engineering mathematics students. The assessment item under development is composed of 2 parts, namely, a set of "pre-lab" homework problems (which focus on relevant prior mathematical knowledge, concepts and skills), and complementary computing laboratory exercises which are undertaken within a fixed (1 hour) time frame. In particular, the computing exercises exploit the algebraic manipulation and visualisation capabilities of the symbolic algebra package MAPLE, with the aim of promoting understanding of certain mathematical concepts and skills via visual and intuitive reasoning, rather than a formal or rigorous approach. The assessment task we are developing is aimed at providing students with a significant learning experience, in addition to providing feedback on their individual knowledge and skills. To this end, a noteworthy feature of the scheme is that marks awarded for the laboratory work are primarily based on the extent to which reflective, critical thinking is demonstrated, rather than the amount of CBE-style tasks completed by the student within the allowed time. With regard to student learning outcomes, a novel and potentially critical feature of our scheme is that the assessment task is designed to be intimately linked to the overall course content, in that it aims to introduce important concepts and skills (via individual student exploration) which will be revisited somewhat later in the pedagogically more restrictive formal lecture component of the course (typically a large group plenary format). Furthermore, the time delay involved, or "incubation period", is also a deliberate design feature: it is intended to allow students the opportunity to undergo potentially important internal re-adjustments in their understanding, before being exposed to lectures on related course content which are invariably delivered in a more condensed, formal and mathematically rigorous manner. In our presentation, we will discuss in more detail our motivation and rationale for trailing such a scheme for the targeted student group. Some of the advantages and disadvantages of our approach (as we perceived them at the initial stages) will also be enumerated. In a companion paper, the theoretical framework for our approach will be more fully elaborated, and measures of student learning outcomes (as obtained from eg. student provided feedback) will be discussed.

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Intelligent software agents are promising in improving the effectiveness of e-marketplaces for e-commerce. Although a large amount of research has been conducted to develop negotiation protocols and mechanisms for e-marketplaces, existing negotiation mechanisms are weak in dealing with complex and dynamic negotiation spaces often found in e-commerce. This paper illustrates a novel knowledge discovery method and a probabilistic negotiation decision making mechanism to improve the performance of negotiation agents. Our preliminary experiments show that the probabilistic negotiation agents empowered by knowledge discovery mechanisms are more effective and efficient than the Pareto optimal negotiation agents in simulated e-marketplaces.

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We argue that web service discovery technology should help the user navigate a complex problem space by providing suggestions for services which they may not be able to formulate themselves as (s)he lacks the epistemic resources to do so. Free text documents in service environments provide an untapped source of information for augmenting the epistemic state of the user and hence their ability to search effectively for services. A quantitative approach to semantic knowledge representation is adopted in the form of semantic space models computed from these free text documents. Knowledge of the user’s agenda is promoted by associational inferences computed from the semantic space. The inferences are suggestive and aim to promote human abductive reasoning to guide the user from fuzzy search goals into a better understanding of the problem space surrounding the given agenda. Experimental results are discussed based on a complex and realistic planning activity.

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Insulin-like growth factor binding proteins (IGFBPs) are prime regulators of IGF-action in numerous cell types including the retinal pigment epithelium (RPE). The RPE performs several functions essential for vision, including growth factor secretion and waste removal via a phagocytic process mediated in part by vitronectin (Vn). In the course of studying the effects of IGFBPs on IGF-mediated VEGF secretion and Vn-mediated phagocytosis in the RPE cell line ARPE-19, we have discovered that these cells avidly ingest synthetic microspheres (2.0 μm diameter) coated with IGFBPs. Given the novelty of this finding and the established role for endocytosis in mediating IGFBP actions in other cell types, we have explored the potential role of candidate cell surface receptors. Moreover, we have examined the role of key IGFBP structural motifs, by comparing responses to three members of the IGFBP family (IGFBP-3, IGFBP-4 and IGFBP-5) which display overlapping variations in primary structure and glycosylation status. Coating of microspheres (FluoSpheres®, sulfate modified polystyrene filled with a fluorophore) was conducted at 37 °C for 1 h using 20 μg/mL of test protein, followed by extensive washing. Binding of proteins was confirmed using a microBCA assay. The negative control consisted of microspheres treated with 0.1% bovine serum albumin (BSA), and all test samples were post-treated with BSA in an effort to coat any remaining free protein binding sites, which might otherwise encourage non-specific interactions with the cell surface. Serum-starved cultures of ARPE-19 cells were incubated with microspheres for 24 h, using a ratio of approximately 100 microspheres per cell. Uptake of microspheres was quantified using a fluorometer and was confirmed visually by confocal fluorescence microscopy. The ARPE-19 cells displayed little affinity for BSA-treated microspheres, but avidly ingested large quantities of those pre-treated with Vn (ANOVA; p < 0.001). Strong responses were also observed towards recombinant formulations of non-glycosylated IGFBP-3, glycosylated IGFBP-3 and glycosylated IGFBP-5 (all p < 0.001), while glycosylated IGFBP-4 induced a relatively minor response (p < 0.05). The response to IGFBP-3 was unaffected in the presence of excess soluble IGFBP-3, IGF-I or Vn. Likewise, soluble IGFBP-3 did not induce uptake of BSA-treated microspheres. Antibodies to either the transferrin receptor or type 1 IGF-receptor displayed slight inhibitory effects on responses to IGFBPs and Vn. Heparin abolished responses to Vn, IGFBP-5 and non-glycosylated IGFBP-3, but only partially inhibited the response to glycosylated IGFBP-3. Our results demonstrate for the first time IGFBP-mediated endocytosis in ARPE-19 cells and suggest roles for the IGFBP-heparin-binding domain and glycosylation status. These findings have important implications for understanding the mechanisms of IGFBP actions on the RPE, and in particular suggest a role for IGFBP-endocytosis.

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For most of the 20th Century a ‘closed’ system of adoption was practised throughout Australia and other modern Western societies. This ‘closed’ system was characterised by sealed records; amended birth certificates to conceal the adoption, and prohibited contact with all biological family. Despite claims that these measures protected these children from the taint of illegitimacy the central motivations were far more complex, involving a desire to protect couples from the stigma of infertility and to provide a socially acceptable family structure (Triseliotis, Feast, & Kyle, 2005; Marshall & McDonald, 2001). From the 1960s significant evidence began to emerge that many adopted children and adults were experiencing higher incidences of psychological difficulties, characterised by problems with psychological adjustment, building self-esteem and forming a secure personal identity. These difficulties became grouped under the term ‘genealogical bewilderment’. As a result, new policies and practices were introduced to try to place the best interests of the child at the forefront. These changes reflected new understandings of adoption; as not only an individual process but also as a social and relational process that continues throughout life. Secrecy and the withholding of birth information are now prohibited in the overwhelming majority of all domestic adoptions processed in Australia (Marshall & McDonald, 2001). One little known consequence of this ‘closed’ system of adoption was the significant number of children who were never told of their adoptive status. As a consequence, some have discovered or had this information disclosed to them, as adults. The first study that looked at the late discovery of genetic origins experiences was conducted by the Post Adoption Resource Centre in New South Wales in 1999. This report found that the participants in their study expressed feelings of disbelief, confusion, anger, sorrow and loss. Further, the majority of participants continued to struggle with issues arising from this intentional concealment of their genetic origins (Perl & Markham, 1999). A second and more recent study (Passmore, Feeney & Foulstone, 2007) looked at the issue of secrecy in adoptive families as part of a broader study of 144 adult adoptees. This study found that secrecy and/or lies or misinformation on the part of adoptive parents had negative effects on both personal identity and relationships with others. The authors noted that those adoptees who found out about their adoption as adults were ‘especially likely to feel a sense of betrayal’ (p.4). Over recent years, stories of secrecy and late discovery have also started to emerge from sperm donor conceived adults (Spencer, 2007; Turner & Coyle, 2000). Current research evidence shows that although a majority of couples during the donor assisted conception process indicate that they intend to tell the offspring about their origins, as many as two-thirds or more of couples continue to withhold this information from their children (Akker, 2006; Gottlieb, A. McWhinnie, 2001; Salter-Ling, Hunter, & Glover, 2001). Why do they keep this secret? Infertility involves a range of complex factors that are often left unresolved or poorly understood by those choosing insemination by donor as a form of family building (Schaffer, J. A., & Diamond, R., 1993). These factors may only impact after the child is born, when resemblance talk becomes most pronounced. Resemblance talk is an accepted form of public discourse and a social convention that legitimises the child as part of the family and is part of the process of constructing the child’s identity within the family. Couples tend to become focused on resemblance as this is where they feel most vulnerable, and the lack of resemblance to the parenting father may trigger his sense of loss (Becker, Butler, & Nachtigall, 2005).

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The integration of computer technologies into everyday classroom life continues to provide pedagogical challenges for school systems, teachers and administrators. Data from an exploratory case study of one teacher and a multiage class of children in the first years of schooling in Australia show that when young children are using computers for set tasks in small groups, they require ongoing support from teachers, and to engage in peer interactions that are meaningful and productive. Classroom organization and the nature of teacher-child talk are key factors in engaging children in set tasks and producing desirable learning and teaching outcomes.

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Large mysticete whales represent a unique challenge for chemical risk assessment. Few epidemiological investigations are possible due to the low incidence of adult stranding events. Similarly their often extreme life-history adaptations of prolonged migration and fasting challenge exposure assumptions. Molecular biomarkers offer the potential to complement information yielded through tissue chemical analysis, as well as providing evidence of a molecular response to chemical exposure. In this study we confirm the presence of cytochrome P450 reductase (CPR) and cytochrome P450 isoenzyme 1A1 (CYP1A1) in epidermal tissue of southern hemisphere humpback whales (Megaptera novaeangliae). The detection of CYP1A1 in the integument of the humpback whale affords the opportunity for further quantitative non-destructive investigations of enzyme activity as a function of chemical stress.

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The enforcement of Intellectual Property rights poses one of the greatest current threats to the privacy of individuals online. Recent trends have shown that the balance between privacy and intellectual property enforcement has been shifted in favour of intellectual property owners. This article discusses the ways in which the scope of preliminary discovery and Anton Piller orders have been overly expanded in actions where large amounts of electronic information is available, especially against online intermediaries (service providers and content hosts). The victim in these cases is usually the end user whose privacy has been infringed without a right of reply and sometimes without notice. This article proposes some ways in which the delicate balance can be restored, and considers some safeguards for user privacy. These safeguards include restructuring the threshold tests for discovery, limiting the scope of information disclosed, distinguishing identity discovery from information discovery, and distinguishing information preservation from preliminary discovery.

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Recent research has begun to address and even compare nascent entrepreneurship and nascent corporate entrepreneurship. An opportunity based view holds great potential to integrate both streams of research, but also presents challenges in how we define corporate entrepreneurship. We extend (corporate) entrepreneurship literature to the opportunity identification phase by providing a framework to classify different types of corporate entrepreneurship. Through analysis of a large dataset on nascent (corporate) entrepreneurship (PSEDII) we show that these corporate entrepreneurs differ largely from each other in terms of human capital. Prior studies have indicated that independent and corporate entrepreneurs pursue different types of opportunities and utilize different strategies. Our findings from the opportunity identification phase challenge those differences and seem to indicate a difference between the opportunities corporate entrepreneurs identify versus the opportunities they exploit.

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In today’s electronic world vast amounts of knowledge is stored within many datasets and databases. Often the default format of this data means that the knowledge within is not immediately accessible, but rather has to be mined and extracted. This requires automated tools and they need to be effective and efficient. Association rule mining is one approach to obtaining knowledge stored with datasets / databases which includes frequent patterns and association rules between the items / attributes of a dataset with varying levels of strength. However, this is also association rule mining’s downside; the number of rules that can be found is usually very big. In order to effectively use the association rules (and the knowledge within) the number of rules needs to be kept manageable, thus it is necessary to have a method to reduce the number of association rules. However, we do not want to lose knowledge through this process. Thus the idea of non-redundant association rule mining was born. A second issue with association rule mining is determining which ones are interesting. The standard approach has been to use support and confidence. But they have their limitations. Approaches which use information about the dataset’s structure to measure association rules are limited, but could yield useful association rules if tapped. Finally, while it is important to be able to get interesting association rules from a dataset in a manageable size, it is equally as important to be able to apply them in a practical way, where the knowledge they contain can be taken advantage of. Association rules show items / attributes that appear together frequently. Recommendation systems also look at patterns and items / attributes that occur together frequently in order to make a recommendation to a person. It should therefore be possible to bring the two together. In this thesis we look at these three issues and propose approaches to help. For discovering non-redundant rules we propose enhanced approaches to rule mining in multi-level datasets that will allow hierarchically redundant association rules to be identified and removed, without information loss. When it comes to discovering interesting association rules based on the dataset’s structure we propose three measures for use in multi-level datasets. Lastly, we propose and demonstrate an approach that allows for association rules to be practically and effectively used in a recommender system, while at the same time improving the recommender system’s performance. This especially becomes evident when looking at the user cold-start problem for a recommender system. In fact our proposal helps to solve this serious problem facing recommender systems.

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Many data mining techniques have been proposed for mining useful patterns in text documents. However, how to effectively use and update discovered patterns is still an open research issue, especially in the domain of text mining. Since most existing text mining methods adopted term-based approaches, they all suffer from the problems of polysemy and synonymy. Over the years, people have often held the hypothesis that pattern (or phrase) based approaches should perform better than the term-based ones, but many experiments did not support this hypothesis. This paper presents an innovative technique, effective pattern discovery which includes the processes of pattern deploying and pattern evolving, to improve the effectiveness of using and updating discovered patterns for finding relevant and interesting information. Substantial experiments on RCV1 data collection and TREC topics demonstrate that the proposed solution achieves encouraging performance.

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This study examined the effect that temporal order within the entrepreneurial discovery-exploitation process has on the outcomes of venture creation. Consistent with sequential theories of discovery-exploitation, the general flow of venture creation was found to be directed from discovery toward exploitation in a random sample of nascent ventures. However, venture creation attempts which specifically follow this sequence derive poor outcomes. Moreover, simultaneous discovery-exploitation was the most prevalent temporal order observed, and venture attempts that proceed in this manner more likely become operational. These findings suggest that venture creation is a multi-scale phenomenon that is at once directional in time, and simultaneously driven by symbiotically coupled discovery and exploitation.