Molecular cloning and sequence analysis of the complestatin biosynthetic gene cluster

Streptomyces lavendulae produces complestatin, a cyclic peptide natural product that antagonizes pharmacologically relevant protein–protein interactions including formation of the C4b,2b complex in the complement cascade and gp120-CD4 binding in the HIV life cycle. Complestatin, a member of the vancomycin group of natural products, consists of an α-ketoacyl hexapeptide backbone modified by oxidative phenolic couplings and halogenations. The entire complestatin biosynthetic and regulatory gene cluster spanning ca. 50 kb was cloned and sequenced. It consisted of 16 ORFs, encoding proteins homologous to nonribosomal peptide synthetases, cytochrome P450-related oxidases, ferredoxins, nonheme halogenases, four enzymes involved in 4-hydroxyphenylglycine (Hpg) biosynthesis, transcriptional regulators, and ABC transporters. The nonribosomal peptide synthetase consisted of a priming module, six extending modules, and a terminal thioesterase; their arrangement and domain content was entirely consistent with functions required for the biosynthesis of a heptapeptide or α-ketoacyl hexapeptide backbone. Two oxidase genes were proposed to be responsible for the construction of the unique aryl-ether-aryl-aryl linkage on the linear heptapeptide intermediate. Hpg, 3,5-dichloro-Hpg, and 3,5-dichloro-hydroxybenzoylformate are unusual building blocks that repesent five of the seven requisite monomers in the complestatin peptide. Heterologous expression and biochemical analysis of 4-hydroxyphenylglycine transaminon confirmed its role as an aminotransferase responsible for formation of all three precursors. The close similarity but functional divergence between complestatin and chloroeremomycin biosynthetic genes also presents a unique opportunity for the construction of hybrid vancomycin-type antibiotics.

Manutenção de sistemas produtivos: um estudo sobre a gestão da disponibilidade de equipamentos.

Este trabalho traduz um estudo de casos, que procura pesquisar e sistematizar o conhecimento sobre a gestão do estado dos equipamentos para atender às suas funções produtivas, isto é, uma gestão orientada para resultados. A função manutenção tem sido considerada como aquela que agrega conhecimentos e atividades para assegurar a disponibilidade operacional dos sistemas produtivos, dentro de padrões de desempenho antecipadamente especificados, ao menor custo possível e atendendo a requisitos pertinentes de segurança. Nesse contexto, pretende-se caracterizar de que modo abordagens ou políticas, adotadas por empresas selecionadas, que requerem o exercício da função manutenção, se vinculam a indicadores de disponibilidade. Ao longo do trabalho, a disponibilidade é tratada como um \"indicador de resultado\" das atividades de manutenção. Transparece da literatura que a análise da tendência desse indicador deve orientar as tomadas de decisão referentes às ações sobre o equipamento. Desse modo, compete verificar se, e como, é feito o vínculo entre esse indicador e decisões relativas à manutenção, sem perder de vista a produtividade da empresa. Assim, descreve-se o contexto em que se inserem a manutenção e a disponibilidade e são identificados elementos que, interferindo na disponibilidade, permitem desdobrá-la e associá-la a uma estrutura analítica que auxilie o levantamento e encaminhamento de análises sobre os dados obtidos no campo, para melhor percepção do tratamento dado à disponibilidade. Para possibilitar o encaminhamento do estudo de casos e a definição das proposições de pesquisa, a função manutenção é associada a um processo, em que se usa o indicador de disponibilidade como feedback, para a otimização do próprio processo de operação da função manutenção, bem como da especificação dos recursos de entrada desse processo. Três proposições são estruturadas e verificadas em quatro empresas que tipificam dois grupos distintos de operações, focalizando o tratamento dado à disponibilidade, e, no seu âmbito, o tratamento de compromissos de gestão e do estudo do ciclo de vida do equipamento. Para possibilitar uma avaliação objetiva das variáveis das proposições da pesquisa, que são de natureza essencialmente qualitativa, encontrou-se, no Capability Maturity Model (CMM), um modelo conceitual que, por suas características evolutivas, forneceu inspiração para estruturar o necessário instrumento de avaliação. A conclusão da pesquisa revela que as proposições de estudo não se confirmaram de forma plena, apontando sensível diferença de seu atendimento quando se faz a comparação entre os dois grupos de empresas, deixando, assim, um espaço em aberto para novas pesquisas.

Optimização de um sistema híbrido off-grid PV, Gerador Diesel e Baterias

Tese de mestrado integrado, Engenharia da Energia e do Ambiente, Universidade de Lisboa, Faculdade de Ciências, 2016

When do adults learn? A cohort analysis of adult education in Europe. CEPS Working Document No. 383, 21 May 2013

Adult learning is seen as a key factor for enhancing employment, innovation and growth, and it should concern all age cohorts. The aim of this paper is to understand the points in the life cycle at which adult learning takes place and whether it leads to reaching a medium or high level of educational attainment. To this end we perform a synthetic panel analysis of adult learning for cohorts aged 25 to 64 in 27 European countries using the European Labour Force Survey. We find, as previous results suggest, that a rise in educational attainment as well as participation in education and training happens mostly at the age range of 25-29. However, investment across the life cycle by cohorts older than 25 still occurs: in most countries in our sample, participation in education and training as well as educational attainment increases observably across all cohorts. We also find that the decline with age slows down or is even reversed for older cohorts, for both participation in education and educational attainment. Finally, we can identify a Nordic model in which adult learning is achieved through participation in education and training, a Central European model in which adult learning occurs in the form of increasing educational attainment and a liberal model in which both approaches to adult learning are observable.

Long-term Pavement Performance Program (LTPP) data analysis support : National Pooled Fund Study TPF-5(013).

"HRDI-13/11-06(500)E"--P. [4] of cover.

Energy analysis of window insulation panels /

Caption title.

An analysis of changing management roles in small Australian services exporters in response to the stages in industry development

Life cycle models have become important in explaining the changing size structure of firms based on the carrying capacity of regions or industries. In particular, the population ecology model predicts stages of growth, maturity and eventually decline in the number of firms in an industry. There has been criticism of such models because of their focus on external variables as pre-determinants of the potential for enterprise development. This paper attempts to reconcile the external focus of the population ecology model with relevant internal management factors in enterprise development. A survey was conducted of Australian services exporters, and the results not only confirm the existence of four separate life cycle stages in the population ecology model, but also identify the external and internal variables that are strategically relevant at each of the stages. The findings provide potentially useful information in a range of contexts including the design of small business assistance as well a providing “guide posts” to entrepreneurs engaged in enterprise development.

In vitro and in silico analysis of signal peptides from the human blood fluke, Schistosoma mansoni

Proteins secreted by and anchored on the surfaces of parasites are in intimate contact with host tissues. The transcriptome of infective cercariae of the blood fluke, Schistosoma mansoni, was screened using signal sequence trap to isolate cDNAs encoding predicted proteins with an N-terminal signal peptide. Twenty cDNA fragments were identified, most of which contained predicted signal peptides or transmembrane regions, including a novel putative seven-transmembrane receptor and a membrane-associated mitogen-activated protein kinase. The developmental expression pattern within different life-cycle stages ranged from ubiquitous to a transcript that was highly upregulated in the cercaria. A bioinformatics-based comparison of 100 signal peptides from each of schistosomes, humans, a parasitic nematode and Escherichia coli showed that differences in the sequence composition of signal peptides, notably the residues flanking the predicted cleavage site, might account for the negative bias exhibited in the processing of schistosome signal peptides in mammalian cells. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

A multiple account framework for cost-benefit analysis

The paper presents a spreadsheet-based multiple account framework for cost-benefit analysis which incorporates all the usual concerns of cost-benefit analysts such as shadow-pricing to account for market failure. distribution of net benefits. sensitivity and risk analysis, cost of public funds, and environmental effects. The approach is generalizable to a wide range of projects and situations and offers a number of advantages to both analysts and decision-makers, including transparency, a check on internal consistency, and a detailed summary of project net benefits disaggregated by stakeholder group. Of particular importance is the ease with which this framework allows for a project to be evaluated from alternative decision-making perspectives and under alternative policy scenarios where the trade-offs among the project's stakeholders can readily be identified and quantified. (C) 2004 Elsevier Ltd. All rights reserved.

ANÁLISE DAS MUDANÇAS DOS FATORES DETERMINANTES DA ESTRUTURA DE CAPITAL EM FUNÇÃO DO CICLO DE VIDA DAS EMPRESAS BRASILEIRAS SÃO BERNARDO DO CAMPO

As várias teorias acerca da estrutura de capital despertam interesse motivando diversos estudos sobre o assunto sem, no entanto, ter um consenso. Outro tema aparentemente pouco explorado refere-se ao ciclo de vida das empresas e como ele pode influenciar a estrutura de capital. Este estudo teve como objetivo verificar quais determinantes possuem maior relevância no endividamento das empresas e se estes determinantes alteram-se dependendo do ciclo de vida da empresa apoiada pelas teorias Trade Off, Pecking Order e Teoria da Agência. Para alcançar o objetivo deste trabalho foi utilizado análise em painel de efeito fixo sendo a amostra composta por empresas brasileiras de capital aberto, com dados secundários disponíveis na Economática® no período de 2005 a 2013, utilizando-se os setores da BM&FBOVESPA. Como resultado principal destaca-se o mesmo comportamento entre a amostra geral, alto e baixo crescimento pelo endividamento contábil para o determinante Lucratividade apresentando uma relação negativa, e para os determinantes Oportunidade de Crescimento e Tamanho, estes com uma relação positiva. Para os grupos de alto e baixo crescimento alguns determinantes apresentaram resultados diferentes, como a singularidade que resultou significância nestes dois grupos, sendo positiva no baixo crescimento e negativa no alto crescimento, para o valor colateral dos ativos e benefício fiscal não dívida apresentaram significância apenas no grupo de baixo crescimento. Para o endividamento a valor de mercado foi observado significância para o Benefício fiscal não dívida e Singularidade. Este resultado reforça o argumento de que o ciclo de vida influência a estrutura de capital

Project risk management:a combined analytic hierarchy process and decision tree approach

Time, cost and quality achievements on large-scale construction projects are uncertain because of technological constraints, involvement of many stakeholders, long durations, large capital requirements and improper scope definitions. Projects that are exposed to such an uncertain environment can effectively be managed with the application of risk management throughout the project life cycle. Risk is by nature subjective. However, managing risk subjectively poses the danger of non-achievement of project goals. Moreover, risk analysis of the overall project also poses the danger of developing inappropriate responses. This article demonstrates a quantitative approach to construction risk management through an analytic hierarchy process (AHP) and decision tree analysis. The entire project is classified to form a few work packages. With the involvement of project stakeholders, risky work packages are identified. As all the risk factors are identified, their effects are quantified by determining probability (using AHP) and severity (guess estimate). Various alternative responses are generated, listing the cost implications of mitigating the quantified risks. The expected monetary values are derived for each alternative in a decision tree framework and subsequent probability analysis helps to make the right decision in managing risks. In this article, the entire methodology is explained by using a case application of a cross-country petroleum pipeline project in India. The case study demonstrates the project management effectiveness of using AHP and DTA.

Construction risk management:a quantitative approach

Conventional project management techniques are not always sufficient for ensuring time, cost and quality achievement of large-scale construction projects due to complexity in planning and implementation processes. The main reasons for project non-achievement are changes in scope and design, changes in Government policies and regulations, unforeseen inflation) under-estimation and improper estimation. Projects that are exposed to such an uncertain environment can be effectively managed with the application of risk numagement throughout project life cycle. However, the effectiveness of risk management depends on the technique in which the effects of risk factors are analysed and! or quantified. This study proposes Analytic Hierarchy Process (AHP), a multiple attribute decision-making technique as a tool for risk analysis because it can handle subjective as well as objective factors in decision model that are conflicting in nature. This provides a decision support system (DSS) to project managenumt for making the right decision at the right time for ensuring project success in line with organisation policy, project objectives and competitive business environment. The whole methodology is explained through a case study of a cross-country petroleum pipeline project in India and its effectiveness in project1nana.gement is demonstrated.

Risk based decision support system for effective implementation of projects

Conventional project management techniques are not always sufficient to ensure time, cost and quality achievement of large-scale construction projects due to complexity in planning, design and implementation processes. The main reasons for project non-achievement are changes in scope and design, changes in government policies and regulations, unforeseen inflation, underestimation and improper estimation. Projects that are exposed to such an uncertain environment can be effectively managed with the application of risk management throughout the project's life cycle. However, the effectiveness of risk management depends on the technique through which the effects of risk factors are analysed/quantified. This study proposes the Analytic Hierarchy Process (AHP), a multiple attribute decision making technique, as a tool for risk analysis because it can handle subjective as well as objective factors in a decision model that are conflicting in nature. This provides a decision support system (DSS) to project management for making the right decision at the right time for ensuring project success in line with organisation policy, project objectives and a competitive business environment. The whole methodology is explained through a case application of a cross-country petroleum pipeline project in India and its effectiveness in project management is demonstrated.

Whole life performance bid evaluation in the Korean public sector

Korea has increasingly adopted design-build for public construction projects in the last few years. There is a much greater awareness of the need to change a system based on ‘Value for Money’ which is high on the government's agenda. A whole life performance bid evaluation model is proposed to aid decision makers in the selection of a design-builder. This is based on the integration of a framework using an analytic hierarchy process as the bid awarding system is being changed from one based on lowest price, to one based on best value over the life-cycle. Key criteria like whole life cost, service life planning and design quality are important through the key stages of evaluation process. The model uses a systematic and holistic approach which enables a public sector to make better decisions in design-builder selection, which will deliver whole life benefits, based on long term cost-effectiveness and whole life.

Assessing economically viable carbon reductions for the production of ammonia from biomass gasification

Greenhouse gas emissions from fertiliser production are set to increase before stabilising due to the increasing demand to secure sustainable food supplies for a growing global population. However, avoiding the impacts of climate change requires all sectors to decarbonise by a very high level within several decades. Economically viable carbon reductions of substituting natural gas reforming with biomass gasification for ammonia production are assessed using techno-economic and life cycle assessment. Greenhouse gas savings of 65% are achieved for the biomass gasification system and the internal rate of return is 9.8% at base-line biomass feedstock and ammonia prices. Uncertainties in the assumptions have been tested by performing sensitivity analysis, which show, for example with a ±50% change in feedstock price, the rate of return ranges between -0.1% and 18%. It would achieve its target rate of return of 20% at a carbon price of £32/t CO, making it cost competitive compared to using biomass for heat or electricity. However, the ability to remain competitive to investors will depend on the volatility of ammonia prices, whereby a significant decrease would require high carbon prices to compensate. Moreover, since no such project has been constructed previously, there is high technology risk associated with capital investment. With limited incentives for industrial intensive energy users to reduce their greenhouse gas emissions, a sensible policy mechanism could target the support of commercial demonstration plants to help ensure this risk barrier is resolved. © 2013 The Authors.