318 resultados para GLOBALLY HYPERBOLIC SPACETIMES


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Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage.

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Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease.

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Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.

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This paper traces the process of invention of adoption of WriteCite.com which is an internet based learning tool used by students to format citation lists. A number of theoretical issues relating to development and deployment of online learning tools are addressed in this paper. A significant finding in this paper is that adoption rate of new technologies amongst students, in this case for WriteCite.com, is not immediately global in nature despite the internet's ubiquity and the existence of internationally accepted bibliographic styles. Rather, and in contrast to neo theories of technology internationalisation, early-stage adoption tends to be geo-centric and concentrated in the US. In the case of WriteCite.com, which has not been sponsored by an academic institution, the findings reflect voluntary rates of globa adoption. From an applied perspective, the process of identifying globally contestable markets is relevant to developers of online learning tools.

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Grass pollens of the temperate (Pooideae) subfamily and subtropical subfamilies of grasses are major aeroallergen sources worldwide. The subtropical Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass) species are abundant in parts of Africa, India, Asia, Australia and the Americas, where a large and increasing proportion of the world's population abide. These grasses are phylogenetically and ecologically distinct from temperate grasses. With the advent of global warming, it is conceivable that the geographic distribution of subtropical grasses and the contribution of their pollen to the burden of allergic rhinitis and asthma will increase. This review aims to provide a comprehensive synthesis of the current global knowledge of (i) regional variation in allergic sensitivity to subtropical grass pollens, (ii) molecular allergenic components of subtropical grass pollens and (iii) allergic responses to subtropical grass pollen allergens in relevant populations. Patients from subtropical regions of the world show higher allergic sensitivity to grass pollens of Chloridoideae and Panicoideae grasses, than to temperate grass pollens. The group 1 allergens are amongst the allergen components of subtropical grass pollens, but the group 5 allergens, by which temperate grass pollen extracts are standardized for allergen content, appear to be absent from both subfamilies of subtropical grasses. Whilst there are shared allergenic components and antigenic determinants, there are additional clinically relevant subfamily-specific differences, at T- and B-cell levels, between pollen allergens of subtropical and temperate grasses. Differential immune recognition of subtropical grass pollens is likely to impact upon the efficacy of allergen immunotherapy of patients who are primarily sensitized to subtropical grass pollens. The literature reviewed herein highlights the clinical need to standardize allergen preparations for both types of subtropical grass pollens to achieve optimal diagnosis and treatment of patients with allergic respiratory disease in subtropical regions of the world. © 2014 John Wiley & Sons Ltd.

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The INFORMAS food prices module proposes a step-wise framework to measure the cost and affordability of population diets. The price differential and the tax component of healthy and less healthy foods, food groups, meals and diets will be benchmarked and monitored over time. Results can be used to model or assess the impact of fiscal policies, such as ‘fat taxes’ or subsidies. Key methodological challenges include: defining healthy and less healthy foods, meals, diets and commonly consumed items; including costs of alcohol, takeaways, convenience foods and time; selecting the price metric; sampling frameworks; and standardizing collection and analysis protocols. The minimal approach uses three complementary methods to measure the price differential between pairs of healthy and less healthy foods. Specific challenges include choosing policy relevant pairs and defining an anchor for the lists. The expanded approach measures the cost of a healthy diet compared to the current (less healthy) diet for a reference household. It requires dietary principles to guide the development of the healthy diet pricing instrument and sufficient information about the population’s current intake to inform the current (less healthy) diet tool. The optimal approach includes measures of affordability and requires a standardised measure of household income that can be used for different countries. The feasibility of implementing the protocol in different countries is being tested in New Zealand, Australia and Fiji. The impact of different decision points to address challenges will be investigated in a systematic manner. We will present early insights and results from this work.

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Knowledge cities are seen as fundamental to the economic growth and development of the 21st century cities. The purpose of this paper is to explore the knowledge city concept in depth. This paper discusses the principles of a knowledge city, and portrays its distinguishing characteristics and processes. The paper relates and analyses Melbourne’s experience as a knowledge city and scrutinises Melbourne’s initiatives on science, technology and innovation and policies for economic and social development. It also illustrates how the city administration played a key role in developing Melbourne as a globally recognised, entrepreneurial and competitive knowledge city. Then this paper identifies key success factors and provides some insights to policy makers of the MENA region cities in designing knowledge cities.

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The process-centered design of organizations and information systems is globally seen as an appropriate response to the increased economic pressure on organizations. At the methodological core of process-centered management is process modeling. However, business process modeling in large initiatives can be a time-consuming and costly exercise, making it potentially difficult to convince executive management of its benefits. To date, and despite substantial interest and research in the area of process modeling, the understanding of the actual benefits of process modeling in academia and practice is limited. To address this gap, this paper explores the perception of benefits derived from process modeling initiatives, as reported through a global Delphi study. The study incorporates the views of three groups of stakeholders – academics, practitioners and vendors. Our findings lead to the first identification and ranking of 19 unique benefits associated with process modeling. The study in particular found that process modeling benefits vary significantly between practitioners and academics. We argue that these variations may point to a dangerous disconnect between research projects and practical demands.

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Our brief is to investigate the role of community and lifestyle in the making of a globally successful knowledge city region. Our approach is essentially pragmatic. We start by broadly examining knowledge-based urban development from a number of different perspectives. The first view is historical. In this context knowledge work and knowledge workers are seen as vital parts of a new emergent mode of production reliant on the continual production of abstract knowledge. We briefly develop this perspective to encompass the work of Richard Florida who has, notedly, claimed: “Wherever talent goes, innovation, creativity, and economic growth are sure to follow.” Our next perspective examines concepts of knowledge and modes of its production to discover knowledge is not an unchanging object but a human activity that changes in form and content through history. The suggestion emerges that not only is the production of contemporary ‘knowledge’ organised in a specific (and new) manner but also the output of this networked production is a particular type of knowledge (i.e. techné). The third perspective locates knowledge production and its workers in the contemporary urban context. As such, it co-ordinates the knowledge city in the increasingly global structure of cities and develops a typology of different groups of knowledge workers in their preferred urban environment(s). We see emerging here a distinctive geography of knowledge production. It is an urban phenomenon. There is, in short, something about the nature of cities that knowledge workers find particularly attractive. In the next, essentially anthropological, perspective we start to explore the needs and desires of the individual knowledge worker. Beyond the needs basic to any modern human household an attempt is made to deduce, from a base understanding of knowledge work as mental labour, the compensatory cultural needs of the knowledge worker when not at work - and the expression of these needs in the urban fabric. Our final perspective consists of two case studies. In a review of the experiences of Austin, Texas and Singapore’s one-north precinct we collect empirical data on, respectively, a knowledge city that has sustained itself for over 50 years and an urban precinct newly launched into the global market for knowledge work and knowledge workers. Interwoven The Role of Community and Lifestyle in the Making of a Knowledge City Urban Research Program 8 through all perspectives, in the form of apposite citation, is that of ‘expert opinion’ gathered in a rudimentary poll of academic and industry sources. This opinion appears in text boxes while details of the survey can be found in Appendix A. In the conclusion of the report we interpret the wide range of evidence gathered above in a policy frame. It is our hope this report will leave the reader with a clearer picture of the decisive organisational, infrastructural, aesthetic and social dimensions of a knowledge precinct.

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The rising problems associated with construction such as decreasing quality and productivity, labour shortages, occupational safety, and inferior working conditions have opened the possibility of more revolutionary solutions within the industry. One prospective option is in the implementation of innovative technologies such as automation and robotics, which has the potential to improve the industry in terms of productivity, safety and quality. The construction work site could, theoretically, be contained in a safer environment, with more efficient execution of the work, greater consistency of the outcome and higher level of control over the production process. By identifying the barriers to construction automation and robotics implementation in construction, and investigating ways in which to overcome them, contributions could be made in terms of better understanding and facilitating, where relevant, greater use of these technologies in the construction industry so as to promote its efficiency. This research aims to ascertain and explain the barriers to construction automation and robotics implementation by exploring and establishing the relationship between characteristics of the construction industry and attributes of existing construction automation and robotics technologies to level of usage and implementation in three selected countries; Japan, Australia and Malaysia. These three countries were chosen as their construction industry characteristics provide contrast in terms of culture, gross domestic product, technology application, organisational structure and labour policies. This research uses a mixed method approach of gathering data, both quantitative and qualitative, by employing a questionnaire survey and an interview schedule; using a wide range of sample from management through to on-site users, working in a range of small (less than AUD0.2million) to large companies (more than AUD500million), and involved in a broad range of business types and construction sectors. Detailed quantitative (statistical) and qualitative (content) data analysis is performed to provide a set of descriptions, relationships, and differences. The statistical tests selected for use include cross-tabulations, bivariate and multivariate analysis for investigating possible relationships between variables; and Kruskal-Wallis and Mann Whitney U test of independent samples for hypothesis testing and inferring the research sample to the construction industry population. Findings and conclusions arising from the research work which include the ranking schemes produced for four key areas of, the construction attributes on level of usage; barrier variables; differing levels of usage between countries; and future trends, have established a number of potential areas that could impact the level of implementation both globally and for individual countries.

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A need for an efficient life care management of building portfolio is becoming increasingly due to increase in aging building infrastructure globally. Appropriate structural engineering practices along with facility management can assist in optimising the remaining life cycle costs for existing public building portfolio. A more precise decision to either demolish, refurbish, do nothing or rebuilt option for any typical building under investigation is needed. In order to achieve this, the status of health of the building needs to be assessed considering several aspects including economic and supply-demand considerations. An investment decision for a refurbishment project competing with other capital works and/or refurbishment projects can be supported by emerging methodology residual service life assessment. This paper discusses challenges in refurbishment projects of public buildings and with a view towards development of residual service life assessment methodology

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With an increase in growing number of aging public building infrastructure globally, there is an opportunity for an efficient life care management rather then mere demolition and rebuild. By carefully implementing appropriate structural engineering practices with facility management, the whole of life cycle costs for public building assets can be optimised and public money can be saved and better utilised elsewhere. A need of decision support tool/methodology which can assist asset manager make better decision among demolish, refurbish, do nothing or rebuilt option for any typical building under consideration is growing in order to optimise maintenance funds. The paper is part of research project focusing on development of such methodology known as residual service life prediction. The paper is mainly focusing on following three major aspects of public building infrastructure; first, issues and challenges in optimisation of maintenance funds, second, residual service life prediction methodology and issues and challenges in the development of such methodology. The paper concludes with the authors’ observations and further research potentials

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Manufacture, construction and use of buildings and building materials make a significant environmental impact internally (inside the building), locally (neighbourhood) and globally. Life cycle assessment (LCA) methodology is being applied for evaluating the environmental impact of building/or building materials. One of the major applications of LCA is to identify key issues of a product system from cradle to grave. Key issues identified in an LCA lead one to the right direction in assessing the environmental aspects of a product system and help to identify the areas for improvement of the environmental performance of a product as well. The purpose of this paper is to suggest two methods for identifying key issues using an integrated tool (LCADesign), which has been developed to provide a method of determining the best alternative for reducing environmental impacts from a building or building materials, and compare both methods in the case study. This paper assists the designers or marketers related to building or building materials in their decision making by giving information on activities or alternatives which are identified as key issues for environmental impacts.

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Global and local studies show that the present growth-based approach to development is unsustainable. If we are serious about surviving the 21st century we will need graduates who are not simply 'globally portable' or even 'globally competent', but also wise global citizens, Globo sapiens. This book contributes to what educators need to know, do and be in order to support transformative learning. The book is based on work with large, socially and culturally diverse, first-year engineering students at an Australian university of technology. It shows that reflective journals, with appropriate planning and support, can be one pillar of a transformative pedagogy which can encourage significant and even transformative attitude change in relation to gender, culture and the environment. It also offers evidence of improved communication skills and other tangible changes to counter common criticisms that such work is "airy-fairy" and irrelevant. The author combines communication theory with critical futures thinking to provide layered understandings of how transformative learning affected students' thinking, learning and behaviour. So the book is both a case-study and a detailed response to the personal and professional challenges that educators all over the world will face as they try to guide students in sustainable directions. It will be useful to teachers in higher education, especially those interested in internationalisation of the curriculum, transformative learning and values change for sustainable futures.