988 resultados para Daisy-chain resistance


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In the project described in this chapter, a group of educationally disengaged high school students investigated their peers' perspectives of factors related to low aspiration for and access to university. On the basis of their findings, they created an informative DVD to address the student needs.

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Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

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A series of polymers with a comb architecture were prepared where the poly(olefin sulfone) backbone was designed to be highly sensitive to extreme ultraviolet (EUV) radiation, while the well-defined poly(methyl methacrylate) (PMMA) arms were incorporated with the aim of increasing structural stability. It is hypothesized that upon EUV radiation rapid degradation of the polysulfone backbone will occur leaving behind the well-defined PMMA arms. The synthesized polymers were characterised and have had their performance as chain-scission EUV photoresists evaluated. It was found that all materials possess high sensitivity towards degradation by EUV radiation (E0 in the range 4–6 mJ cm−2). Selective degradation of the poly(1-pentene sulfone) backbone relative to the PMMA arms was demonstrated by mass spectrometry headspace analysis during EUV irradiation and by grazing-angle ATR-FTIR. EUV interference patterning has shown that materials are capable of resolving 30 nm 1:1 line:space features. The incorporation of PMMA was found to increase the structural integrity of the patterned features. Thus, it has been shown that terpolymer materials possessing a highly sensitive poly(olefin sulfone) backbone and PMMA arms are able to provide a tuneable materials platform for chain scission EUV resists. These materials have the potential to benefit applications that require nanopattering, such as computer chip manufacture and nano-MEMS.

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In this research we examined, by means of case studies, the mechanisms by which relationships can be managed and by which communication and cooperation can be enhanced in developing sustainable supply chains. The research was predicated on the contention that the development of a sustainable supply chain depends, in part, on the transfer of knowledge and capabilities from the larger players in the supply chain. A sustainable supply chain requires proactive relationship management and the development of an appropriate organisational culture, and trust. By legitimising individuals’ expectations of the type of culture which is appropriate to their company and empowering employees to address mismatches that may occur, a situation can be created whereby the collaborating organisations develop their competences symbiotically and so facilitate a sustainable supply chain. Effective supply chain management enhances organisation performance and competitiveness through the management of operations across organisational boundaries. Relational contracting approaches facilitate the exchange of information and knowledge and build capacity in the supply chain, thus enhancing its sustainability. Relationship management also provides the conditions necessary for the development of collaborative and cooperative relationships However, often subcontractors and suppliers are not empowered to attend project meetings or to have direct communication with project based staff. With this being a common phenomenon in the construction industry, one might ask: what are the barriers to implementation of relationship management through the supply chain? In other words, the problem addressed in this research is the engagement of the supply chain through relationship management.

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For the 2005 season, Mackay Sugar and its growers agreed to implement a new cane payment system. The aim of the new system was to better align the business drivers between the mill and its growers and as a result improve business decision making. The technical basis of the new cane payment system included a fixed sharing of the revenue from sugar cane between the mill and growers. Further, the new system replaced the CCS formula with a new estimate of recoverable sugar (PRS) and introduced NIR for payment analyses. Significant mill and grower consultation processes led to the agreement to implement the new system in 2005 and this consultative approach has been reflected in two seasons of successful operation.

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Objective: To assess the cost-effectiveness of screening, isolation and decolonisation strategies in the control of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs). Design: Economic evaluation. Setting: England and Wales. Population: ICU patients. Main outcome measures: Infections, deaths, costs, quality adjusted life years (QALYs), incremental cost-effectiveness ratios for alternative strategies, net monetary benefits (NMBs). Results: All strategies using isolation but not decolonisation improved health outcomes but increased costs. When MRSA prevalence on admission to the ICU was 5% and the willingness to pay per QALY gained was between £20,000 and £30,000, the best such strategy was to isolate only those patients at high risk of carrying MRSA (either pre-emptively or following identification by admission and weekly MRSA screening using chromogenic agar). Universal admission and weekly screening using polymerase chain reaction (PCR)-based MRSA detection coupled with isolation was unlikely to be cost-effective unless prevalence was high (10% colonised with MRSA on admission to the ICU). All decolonisation strategies improved health outcomes and reduced costs. While universal decolonisation (regardless of MRSA status) was the most cost-effective in the short-term, strategies using screening to target MRSA carriers may be preferred due to reduced risk of selecting for resistance. Amongst such targeted strategies, universal admission and weekly PCR screening coupled with decolonisation with nasal mupirocin was the most cost-effective. This finding was robust to ICU size, MRSA admission prevalence, the proportion of patients classified as high-risk, and the precise value of willingness to pay for health benefits. Conclusions: MRSA control strategies that use decolonisation are likely to be cost-saving in an ICU setting provided resistance is lacking, and combining universal PCR-based screening with decolonisation is likely to represent good value for money if untargeted decolonisation is considered unacceptable. In ICUs where decolonisation is not implemented there is insufficient evidence to support universal MRSA screening outside high prevalence settings.

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There is little empirical research on the relational capabilities and competences in supply chain relationships, and the important links that exist between relational capabilities, competences and supply chain innovation. This study addresses some of that knowledge gap gained through a case study of the Australian freight services sector. Findings suggest that different competences developed by supply chain participants support different ways to enable operational effectiveness. Road freight businesses should acquire knowledge of how to select and manage inter-firm relationships that provide the greatest benefit, acquiring competences that either improve their current capabilities or assist them to explore strategies that ensure incremental innovation and supply chain performance objectives are met.

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Increasing global competitiveness worldwide has forced manufacturing organizations to produce high-quality products more quickly and at a competitive cost. In order to reach these goals, they need good quality components from suppliers at optimum price and lead time. This actually forced all the companies to adapt different improvement practices such as lean manufacturing, Just in Time (JIT) and effective supply chain management. Applying new improvement techniques and tools cause higher establishment costs and more Information Delay (ID). On the contrary, these new techniques may reduce the risk of stock outs and affect supply chain flexibility to give a better overall performance. But industry people are unable to measure the overall affects of those improvement techniques with a standard evaluation model .So an effective overall supply chain performance evaluation model is essential for suppliers as well as manufacturers to assess their companies under different supply chain strategies. However, literature on lean supply chain performance evaluation is comparatively limited. Moreover, most of the models assumed random values for performance variables. The purpose of this paper is to propose an effective supply chain performance evaluation model using triangular linguistic fuzzy numbers and to recommend optimum ranges for performance variables for lean implementation. The model initially considers all the supply chain performance criteria (input, output and flexibility), converts the values to triangular linguistic fuzzy numbers and evaluates overall supply chain performance under different situations. Results show that with the proposed performance measurement model, improvement area for each variable can be accurately identified.

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Many studies into construction procurement methods reveal evidence of a need to change the culture and attitude in the construction industry, transition from traditional adversarial relationships to cooperative and collaborative relationships. At the same time there is also increasing concern and discussion on alternative procurement methods, involving a movement away from traditional procurement systems. Relational contracting approaches, such as partnering and relationship management, are business strategies that align the objectives of clients, commercial participants and stakeholders. It provides a collaborative environment and a framework for all participants to adapt their behaviour to project objectives and allows for engagement of those subcontractors and suppliers down the supply chain. The efficacy of relationship management in the client and contractor groups is proven and well documented. However, the industry has a history of slow implementation of relational contracting down the supply chain. Furthermore, there exists little research on relationship management conducted in the supply chain context. This research aims to explore the association between relational contracting structures and processes and supply chain sustainability in the civil engineering construction industry. It endeavours to shed light on the practices and prerequisites for relationship management implementation success and for supply sustainability to develop. The research methodology is a triangulated approach based on Cheung.s (2006) earlier research where questionnaire survey, interviews and case studies were conducted. This new research includes a face-to-face questionnaire survey that was carried out with 100 professionals from 27 contracting organisations in Queensland from June 2008 to January 2009. A follow-up survey sub-questionnaire, further examining project participants. perspectives was sent to another group of professionals (as identified in the main questionnaire survey). Statistical analysis including multiple regression, correlation, principal component factor analysis and analysis of variance were used to identify the underlying dimensions and test the relationships among variables. Interviews and case studies were conducted to assist in providing a deeper understanding as well as explaining findings of the quantitative study. The qualitative approaches also gave the opportunity to critique and validate the research findings. This research presents the implementation of relationship management from the contractor.s perspective. Findings show that the adaption of relational contracting approach in the supply chain is found to be limited; contractors still prefer to keep the suppliers and subcontractors at arm.s length. This research shows that the degree of match and mismatch between organisational structuring and organisational process has an impact on staff.s commitment level and performance effectiveness. Key issues affecting performance effectiveness and relationship effectiveness include total influence between parties, access to information, personal acquaintance, communication process, risk identification, timely problem solving and commercial framework. Findings also indicate that alliance and Early Contractor Involvement (ECI) projects achieve higher performance effectiveness at both short-term and long-term levels compared to projects with either no or partial relationship management adopted.

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Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most devastating diseases of banana (Musa spp.). Apart from resistant cultivars, there are no effective control measures for the disease. We investigated whether the transgenic expression of apoptosis-inhibition related genes in banana could be used to confer disease resistance. Embryogenic cell suspensions of the banana cultivar, ‘Lady Finger’, were stably transformed with animal genes that negatively regulate apoptosis, namely Bcl-xL, Ced-9 and Bcl-2 3’ UTR, and independently transformed plant lines were regenerated for testing. Following a 12 week exposure to Foc race 1 in small-plant glasshouse bioassays, seven transgenic lines (2 x Bcl-xL, 3 x Ced-9 and 2 x Bcl-2 3’ UTR) showed significantly less internal and external disease symptoms than the wild-type susceptible ‘Lady Finger’ banana plants used as positive controls. Of these, one Bcl-2 3’ UTR line showed resistance that was equivalent to that of wild-type Cavendish bananas that were included as resistant negative controls. Further, the resistance of this line continued for 23 weeks post-inoculation at which time the experiment was terminated. Using TUNEL assays, Foc race 1 was shown to induce apoptosis-like features in the roots of wild-type ‘Lady Finger’ plants consistent with a necrotrophic phase in the lifecycle of this pathogen. This was further supported by the observed reduction of these effects in the roots of the resistant Bcl-2 3’ UTR transgenic line. This is the first report on the generation of transgenic banana plants with resistance to Fusarium wilt.

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BACKGROUND: Enterococcus faecalis and Enterococcus faecium are associated with faecal pollution of water, linked to swimmer-associated gastroenteritis and demonstrate a wide range of antibiotic resistance. The Coomera River is a main water source for the Pimpama-Coomera watershed and is located in South East Queensland, Australia, which is used intensively for agriculture and recreational purposes. This study investigated the diversity of E. faecalis and E. faecium using Single Nucleotide Polymorphisms (SNPs) and associated antibiotic resistance profiles. RESULTS: Total enterococcal counts (cfu/ml) for three/six sampling sites were above the United States Environmental Protection Agency (USEPA) recommended level during rainfall periods and fall into categories B and C of the Australian National Health and Medical Research Council (NHMRC) guidelines (with a 1-10% gastrointestinal illness risk). E. faecalis and E. faecium isolates were grouped into 29 and 23 SNP profiles (validated by MLST analysis) respectively. This study showed the high diversity of E. faecalis and E. faecium over a period of two years and both human-related and human-specific SNP profiles were identified. 81.8% of E. faecalis and 70.21% of E. faecium SNP profiles were associated with genotypic and phenotypic antibiotic resistance. Gentamicin resistance was higher in E. faecalis (47% resistant) and harboured the aac(6')-aph(2') gene. Ciprofloxacin resistance was more common in E. faecium (12.7% resistant) and gyrA gene mutations were detected in these isolates. Tetracycline resistance was less common in both species while tet(L) and tet(M) genes were more prevalent. Ampicillin resistance was only found in E. faecium isolates with mutations in the pbp5 gene. Vancomycin resistance was not detected in any of the isolates. We found that antibiotic resistance profiles further sub-divided the SNP profiles of both E. faecalis and E. faecium. CONCLUSIONS: The distribution of E. faecalis and E. faecium genotypes is highly diverse in the Coomera River. The SNP genotyping method is rapid and robust and can be applied to study the diversity of E. faecalis and E. faecium in waterways. It can also be used to test for human-related and human-specific enterococci in water. The resolving power can be increased by including antibiotic-resistant profiles which can be used as a possible source tracking tool. This warrants further investigation.

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Small business has been shown to contribute significantly to a nation’s economic development. Small business owners typically confront challenges, uncertainty, and risks while operating new businesses. Franchising has become a way to minimize the risks of small business management (Chiou et al., 2004); however, a franchise system is not a guarantee of business success (Lee and Karkovista, 2001). A poor franchising relationship between franchisors and franchisees can result in franchise failure, such as termination and closure, or franchisee exit (Frazer and Winzar, 2005).