220 resultados para 108-666A
Resumo:
Heparan sulfate (HS) is a linear, highly variable, highly sulfated glycosaminoglycan sugar whose biological activity largely depends on internal sulfated domains that mediate specific binding to an extensive range of proteins. In this study we employed anion exchange chromatography, molecular sieving and enzymatic cleavage on HS fractions purified from three compartments of cultured osteoblasts-soluble conditioned media, cell surface, and extracellular matrix (ECM). We demonstrate that the composition of HS chains purified from the different compartments is structurally non-identical by a number of parameters, and that these differences have significant ramifications for their ligand-binding properties. The HS chains purified of conditioned medium had twice the binding affinity for FGF2 when compared with either cell surface or ECM HS. In contrast, similar binding of BMP2 to the three types of HS was observed. These results suggest that different biological compartments of cultured cells have structurally and functionally distinct HS species that help to modulate the flow of HS-dependent factors between the ECM and the cell surface.
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To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia.
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This paper discusses the vibration characteristics of a concrete-steel composite multi-panel floor structure; the use of these structures is becoming more common. These structures have many desirable properties but are prone to excessive and complex vibration, which is not currently well understood. Existing design codes and practice guides provide generic advice or simple techniques that cannot address the complex vibration in these types of low-frequency structures. The results of this study show the potential for an adverse dynamic response from higher and multi-modal excitation influenced by human-induced pattern loading, structural geometry, and activity frequency. Higher harmonics of the load frequency are able to excite higher modes in the composite floor structure in addition to its fundamental mode. The analytical techniques used in this paper can supplement the current limited code and practice guide provisions for mitigating the impact of human-induced vibrations in these floor structures.
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Design-Build (DB) project delivery systems have increasingly been adopted by many private and public sector organizations worldwide due to its many advantages. However, many Indonesian road infrastructure projects are still delivered using the traditional design-bid-build (DBB) project delivery system. This paper reviews the existing literature to explore factors that can influence the successful implementation of DB project delivery system in Indonesian road infrastructure projects. It founds the lack of clarification in existing legislations as well as the lack of experiences, knowledge and skill as the main obstacles in implementing DB systems in Indonesia. To overcome these obstacles, this paper proposes (1) A relook at existing legislation in term of providing more guidance on determining projects appropriate for the DB, procedures for implementing DB, and the structure of builder entity; (2) To develop the skills and knowledge of DB to all stakeholders through communications, knowledge sharing and training. The outcome of this review can serve as a guide to development a framework for the implementation of the design-build project delivery system in Indonesian road infrastructure projects.
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This study examined the sources of stress experienced by occupational therapists and social workers employed in Australian public mental health services and identified the demographic and work-related factors related to stress using a cross-sectional survey design. Participants provided demographic and work-related information and completed the Mental Health Professionals Stress Scale. The overall response rate to the survey was 76.6%, consisting of 196 occupational therapists and 108 social workers. Results indicated that lack of resources, relationships and conflicts with other professionals, workload, and professional self-doubt were correlated with increased stress. Working in case management was associated with stress caused by client-related difficulties, lack of resources, and professional self-doubt. The results of this study suggest that Australian occupational therapists and social workers experience stress, with social workers reporting slightly more overall stress than occupational therapists.
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There are several ways that the Commissioner of Taxation may indirectly obtain priority over unsecured creditors. This is contrary to the principle of pari passu, a principle endorsed by the 1988 Harmer Report as one that is a fundamental objective of the law of insolvency. As the law and practice of Australia's taxation regime evolves, the law is being drafted in a manner that is inconsistent with the principle of pari passu. The natural consequence of this development is that it places at risk the capacity of corporate and bankruptcy laws to coexist and cooperate with taxation laws. This article posits that undermining the consistency of Commonwealth legislative objectives is undesirable. The authors suggest that one means of addressing the inconsistency is to examine whether there is a clearly aligned theoretical basis for the development of these areas of law and the extent that alignment addresses these inconsistencies. This forms the basis for the recommendations made around such inconsistencies using statutory priorities as an exemplar.
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Background We investigated the geographical variation of water supply and sanitation indicators (WS&S) and their role to the risk of schistosomiasis and hookworm infection in school age children in West Africa. The aim was to predict large-scale geographical variation in WS&S, quantify the attributable risk of S. haematobium, S. mansoni and hookworm infections due to WS&S and identify communities where sustainable transmission control could be targeted across the region. Methods National cross-sectional household-based demographic health surveys were conducted in 24,542 households in Burkina Faso, Ghana and Mali, in 2003–2006. We generated spatially-explicit predictions of areas without piped water, toilet facilities and finished floors in West Africa, adjusting for household covariates. Using recently published helminth prevalence data we developed Bayesian geostatistical models (MGB) of S. haematobium, S. mansoni and hookworm infection in West Africa including environmental and the mapped outputs for WS&S. Using these models we estimated the effect of WS&S on parasite risk, quantified their attributable fraction of infection, and mapped the risk of infection in West Africa. Findings Our maps show that most areas in West Africa are very poorly served by water supply except in major urban centers. There is a better geographical coverage for toilet availability and improved household flooring. We estimated smaller attributable risks for water supply in S. mansoni (47%) compared to S. haematobium (71%), and 5% of hookworm cases could be averted by improving sanitation. Greater levels of inadequate sanitation increased the risk of schistosomiasis, and increased levels of unsafe water supply increased the risk of hookworm. The role of floor type for S. haematobium infection (21%) was comparable to that of S. mansoni (16%), but was significantly higher for hookworm infection (86%). S. haematobium and hookworm maps accounting for WS&S show small clusters of maximal prevalence areas in areas bordering Burkina Faso and Mali smaller. The map of S. mansoni shows that this parasite is much more wide spread across the north of the Niger River basin than previously predicted. Interpretation Our maps identify areas where the Millennium Development Goal for water and sanitation is lagging behind. Our results show that WS&S are important contributors to the burden of major helminth infections of children in West Africa. Including information about WS&S as well as the “traditional” environmental risk factors in spatial models of helminth risk yielded a substantial gain both in model fit and at explaining the proportion of spatial variance in helminth risk. Mapping the distribution of infection risk adjusted for WS&S allowed the identification of communities in West Africa where integrative preventive chemotherapy and engineering interventions will yield the greatest public health benefits.
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On obstacle-cluttered construction sites where heavy equipment is in use, safety issues are of major concern. The main objective of this paper is to develop a framework with algorithms for obstacle avoidance and path planning based on real-time three-dimensional job site models to improve safety during equipment operation. These algorithms have the potential to prevent collisions between heavy equipment vehicles and other on-site objects. In this study, algorithms were developed for image data acquisition, real-time 3D spatial modeling, obstacle avoidance, and shortest path finding and were all integrated to construct a comprehensive collision-free path. Preliminary research results show that the proposed approach is feasible and has the potential to be used as an active safety feature for heavy equipment.
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As part of a development plan-in-progress spanning a total of 25 years(1996 to 2020), Malaysia’s Multimedia Super Corridor (MSC) provides a unique opportunity to witness a brief and microcosmic unfolding of the reciprocally formative process between society and technology that Lewis Mumford lays out in exhaustive detail in Technics and Civilization (Mumford, 1963). The interlocking of national imagining, destiny and progress with a specific group of technologies, information and communication technologies(ICT) is, in itself, worthy of interest. However, what renders the MSC doubly remarkable is its introduction in Malaysia, one of the most well established of contemporary ethnocracies. This chapter reads the development and implementation of the MSC as the text through which the association between nation and ethnicity is examined. Broadly speaking I argue here that the MSC inflects the imagining(s) of Malaysia at two levels. At the first level where the MSC is understood to be the insertion of a new policy into Malaysia’s pre existent ethnocratic climate, I contend the MSC inflects the nation through its incongruence with prevalent conditions. At the second level, where the MSC is viewed through the position of its Chinese populace, I suggest that the MSC inflects Malaysia (perhaps to a lesser degree) through the re-emphasis it lends to issues of transnationalism and belonging for the Malaysian Chinese.
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Commissioned by SBS, and published in March 2006, Connecting Diversity: Paradoxes of Multicultural Australia is a follow-up study to SBS’s 2002 report, Living Diversity: Australia’s Multicultural Future. The attitudes of many younger Australians from culturally diverse backgrounds reveal paradoxes about Australian multiculturalism today. This report sheds light on their views, experiences and expectations and the role of media in their lives. Younger, culturally and linguistically diverse Australians are often the subject of mediafanned controversy about disaffection, ‘ethnic gangs’ and cultural isolation. While these controversies tend to be localised – Cronulla, Inala or Bankstown – Connecting Diversity tells a national and quite different story. This research builds upon the findings of the 2002 report, Living Diversity: Australia’s Multicultural Future, which challenged common assumptions about contemporary multicultural Australia. In an era of fragmenting media and assumed political apathy, Connecting Diversity further examines many of the findings of the earlier study, with a new focus on younger people, cultural identity and media use. Connecting Diversity reveals individual experiences and often contradictory ideas about media and diversity in Australia. Disjunctions appear to exist between an individual’s experience and their thoughts about Australia’s national identity. Multiculturalism is valued for broadening the appreciation of difference, yet this support can coexist with concerns about perceived segregation, usually ‘elsewhere’ in Australia. Younger people tend to be more comfortable with cultural difference than previous generations and cite their own diverse network of friends as one of the reasons for this. Even so, some describe experiences of racism that engender a feeling of exclusion from ‘mainstream’ society. In their everyday lives, social relationships are navigated through regular and familiar connections on the one hand, and experiences and expressions of disconnection on the other. Racism and tolerance may be expressed almost simultaneously. These disconnections are often managed through ‘practical tolerance',allowing them to negotiate these apparent contradictions. The connections can be based simultaneously on such things as work, family,religion, friendships or location. The result is a multilayered sense of personal belonging and community connection. A large number of respondents in these focus groups expressed frustration at the failings of media, especially news and current affairs coverage, yet spoke enthusiastically about the accessibility and range of media compared to what was available to previous generations. In their many forms, media remain a key ingredient of self-identification among younger Australians of culturally diverse backgrounds who are especially cynical about media and disillusioned by their perceived inability to influence issues that are important to them. These findings reveal that although they may be cynical about media messages, these younger Australians are looking for connection through media and are seeking ways to participate in meaningful ways. This raises questions about the possibilities for media to empower younger people to play a part in genuine cultural democracy. By capturing the attitudes of Australians of culturally diverse backgrounds under the age of 40, Connecting Diversity: Paradoxes of Multicultural Australia provides an insight into social trends and the generational and cultural changes that are now shaping Australia.
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Rats are superior to the most advanced robots when it comes to creating and exploiting spatial representations. A wild rat can have a foraging range of hundreds of meters, possibly kilometers, and yet the rodent can unerringly return to its home after each foraging mission, and return to profitable foraging locations at a later date (Davis, et al., 1948). The rat runs through undergrowth and pipes with few distal landmarks, along paths where the visual, textural, and olfactory appearance constantly change (Hardy and Taylor, 1980; Recht, 1988). Despite these challenges the rat builds, maintains, and exploits internal representations of large areas of the real world throughout its two to three year lifetime. While algorithms exist that allow robots to build maps, the questions of how to maintain those maps and how to handle change in appearance over time remain open. The robotic approach to map building has been dominated by algorithms that optimise the geometry of the map based on measurements of distances to features. In a robotic approach, measurements of distance to features are taken with range-measuring devices such as laser range finders or ultrasound sensors, and in some cases estimates of depth from visual information. The features are incorporated into the map based on previous readings of other features in view and estimates of self-motion. The algorithms explicitly model the uncertainty in measurements of range and the measurement of self-motion, and use probability theory to find optimal solutions for the geometric configuration of the map features (Dissanayake, et al., 2001; Thrun and Leonard, 2008). Some of the results from the application of these algorithms have been impressive, ranging from three-dimensional maps of large urban strucutures (Thrun and Montemerlo, 2006) to natural environments (Montemerlo, et al., 2003).
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This position paper provides an overview of work conducted and an outlook of future directions within the field of Information Retrieval (IR) that aims to develop novel models, methods and frameworks inspired by Quantum Theory (QT).
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Design-build (DB) system has been demonstrated as an effective delivery method and been widely used overseas. However it does not receive the same popularity in the People’s Republic of China (PRC). This paper first conducts a literature review on advantages and disadvantages of DB in general; then it gives an overview of the PRC construction industry. There are ample evidences that the DB system will theoretically bring benefits to the PRC construction industry. After a thorough investigation of the current DB market, it can be concluded that the development of the DB system is still at its infancy stage. The barriers to entry have been finally identified, which relate to the legal restraints, negative owner attitude, and high requirement of DB projects. These barriers constitute obstacles to the development of DB system in the PRC. However, with rapid growth of construction industry, new requirements in modern construction projects, and strong promotion from governments, it is believed that the domestic DB market will have great potential in the near future.