76 resultados para Interdependency
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The manner by which effects of simultaneous mutations combine to change enzymatic activity is not easily predictable because these effects are not always additive in a linear manner. Hence, the characterization of the effects of simultaneous mutations of amino acid residues that bind the substrate can make a significant contribution to the understanding of the substrate specificity of enzymes. In the β-glycosidase from Spodoptera frugiperda (Sfβgly), both residues Q39 and E451 interact with the substrate and this is essential for defining substrate specificity. Double mutants of Sfβgly (A451E39, S451E39 and S451N39) were prepared by site-directed mutagenesis, expressed in bacteria and purified using affinity chromatography. These enzymes were characterized using p-nitrophenyl β-galactoside and p-nitrophenyl β-fucoside as substrates. The k cat/Km ratio for single and double mutants of Sfβgly containing site-directed mutations at positions Q39 and E451 was used to demonstrate that the effect on the free energy of ES‡ (enzyme-transition state complex) of the double mutations (∆∆G‡xy) is not the sum of the effects resulting from the single mutations (∆∆G‡x and ∆∆G‡y). This difference in ∆∆G‡ indicates that the effects of the single mutations partially overlap. Hence, this common effect counts only once in ∆∆G‡xy. Crystallographic data on β-glycosidases reveal the presence of a bidentate hydrogen bond involving residues Q39 and E451 and the same hydroxyl group of the substrate. Therefore, both thermodynamic and crystallographic data suggest that residues Q39 and E451 exert a mutual influence on their respective interactions with the substrate.
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There remains uncertainty in scientific discussions regarding the governance of universities in new public management regimes in terms of who actually 'rules' in the university. Apparently, a strengthened management leadership is confronted with continuing elements of academic self-regulation and professional autonomy in knowledge production and diffusion. Organisational and academic rationales coexist in today's management of universities. This article endeavours to clarify some of the ambiguities pertaining to the coexistence of two authorities by demonstrating the working of 'interdependency management' that is taking place within universities. For this purpose, the authors have scrutinised research, teaching and recruitment policies in one Swiss university that is subject to such ambiguities. The study confirms existing research in that a command-and-control system is not applied. Policymaking in universities is instead based on a mix of negotiations in faculties that are taking place in the 'shadow of hierarchy', negotiated bargaining between faculties and leaders and occasional unilateral decisions of leaders. This mitigates latent conflicts between management and the academic community: strategic orientations of the university are generally accepted by the academic community while the academic community has influence on policy formulation and maintains defining powers over policy substance.
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Project management has evolved in recent decades. Project portfolio management, together with multi project management, is an emerging area in the project management field in practice, and correspondingly in academic research and forums. In multi project management, projects cannot be handled isolated from each other, as they often have interdependencies that have to be taken into account. If the interdependencies between projects are evaluated during the selection process, the success rate of the project portfolio is increased. Interdependencies can be human resources, technological, and/or market based. Despite of the fact that interdependency as a phenomenon has roots in the 1960s and is related to famous management theories, it has not been much studied, although in practice most companies use it to great extent. There exists some research on interdependency, but prior publications have not emphasized the phenomenon per se, because a practical orientation practitioner techniques prevails in the literature. This research applies the method triangulation, electronic surveys and multiple case study. The research concentrates on small to large companies in Estonia and Finland, mainly in construction, engineering, ICT, and machinery industries. The literature review reveals that interdependencies are deeply involved in R&D and innovation. Survey analysis shows that companies are aware of interdependency issues in general, but they i have lack of detailed knowledge to use it thoroughly. Empirical evidence also indicates that interdependency techniques influence the success rate and other efficiency aspects to different extents. There are a lot of similarities in interdependency related managerial issues in companies of varying sizes and countries in Northern Europe. Differences found in the study are for instance the fact that smaller companies face more difficulties in implementing and evaluating interdependency procedures. Country differences between Estonia and Finland stem from working solutions to manage interdependencies on a daily basis.historical and cultural reasons, such as the special features of a transition country compared to a mature country. An overview of the dominant problems, best practices, and commonly used techniques associated with interdependency is provided in the study. Empirical findings show that many interdependency techniques are not used in practice. A multiple case study was performed in the study to find out how interdependencies are managed in real life on a daily basis. The results show that interdependencies are mostly managed in an informal manner. A description of managing the interdependencies and implementation procedures is given. Interdependency procedures are hard to implement, especially in smaller companies. Companies have difficulties in implementing interdependency procedures and evaluating them. The study contains detailed results on how companies have implemented working solutions to manage interdependencies on a daily basis
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The manner by which effects of simultaneous mutations combine to change enzymatic activity is not easily predictable because these effects are not always additive in a linear manner. Hence, the characterization of the effects of simultaneous mutations of amino acid residues that bind the substrate can make a significant contribution to the understanding of the substrate specificity of enzymes. In the β-glycosidase from Spodoptera frugiperda (Sfβgly), both residues Q39 and E451 interact with the substrate and this is essential for defining substrate specificity. Double mutants of Sfβgly (A451E39, S451E39 and S451N39) were prepared by site-directed mutagenesis, expressed in bacteria and purified using affinity chromatography. These enzymes were characterized using p-nitrophenyl β-galactoside and p-nitrophenyl β-fucoside as substrates. The k cat/Km ratio for single and double mutants of Sfβgly containing site-directed mutations at positions Q39 and E451 was used to demonstrate that the effect on the free energy of ES‡ (enzyme-transition state complex) of the double mutations (∆∆G‡xy) is not the sum of the effects resulting from the single mutations (∆∆G‡x and ∆∆G‡y). This difference in ∆∆G‡ indicates that the effects of the single mutations partially overlap. Hence, this common effect counts only once in ∆∆G‡xy. Crystallographic data on β-glycosidases reveal the presence of a bidentate hydrogen bond involving residues Q39 and E451 and the same hydroxyl group of the substrate. Therefore, both thermodynamic and crystallographic data suggest that residues Q39 and E451 exert a mutual influence on their respective interactions with the substrate.
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Interdependency and Care over the Lifecourse draws upon theories of time and space to consider how informal care is woven into the fabric of everyday lives and is shaped by social and economic inequalities and opportunities. The book comprises three parts. The first explores contrasting social and economic contexts of informal care in different parts of the world. The second looks at different themes and dynamics of caring, using fictional vignettes of illness and health, child care, elderly care and communities of care. The book examines the significance to practices of care throughout the lifecourse of: understandings and expectations of care emotional exchanges involved in care memories and anticipations of giving and receiving care the social nature of the spaces and places in which care is carried out the practical time-space scheduling necessary to caring activities. Finally the authors critically examine how the frameworks of caringscapes and carescapes might be used in research, policy and practice. A working example is provided. This book will be of interest to students and researchers of care work, health and social care, geography, sociology of the family and social policy as well as those in business and policy communities trying to gain an understanding of how work and informal care interweave
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Green innovation, which enables us to extract energy from food crops, caused a food shortage in 2008. Countries suffering severe damage started to reconsider their agricultural policy with the aim of becoming more autonomous. The food price hike of the time looks like a reversal of the celebrated Singer-Prebisch thesis proposed in the 1950s. This paper examines the consequences of this trend on the comparative advantages and development strategies of developing countries. For that purpose, first, trends and short-run fluctuations in the prices of fuel and bio-energy crops are investigated. It is shown that the price series of fuels and the crops are synchronized only after the fuel extracting technology came into effect. Second, the reversal of the Singer-Prebisch thesis is underpinned by the generic form of an endogenous growth model developed by Rebelo (1991). It is shown that as an economy grows, appreciation of the non-reproducible, such as mineral resources and raw labor, over the reproducible, such as capital goods, is the norm rather than an anomaly. Third, the consequences of the food price hike and underlying capital accumulation on the development strategies of labor-abundant and low-income countries are explored. It is concluded that the impact of the food price hikes on the alteration of a development strategy is only incremental, without reinforcement from raw-labor-saving innovation. A case study of inventions by JUKI Corporation, a world-leader in the sewing machine market exemplifies the fact that, of all the major inventions the company have made, raw-labor-saving inventions have not dominated, although JUKI's machines are sold to one of the most raw-labor-intensive industries.
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"December 6, 1985."
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Universidade Estadual de Campinas . Faculdade de Educação Física
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The study of Information Technology (IT) outsourcing is relevant because companies are outsourcing their activities more than ever. An important IT outsourcing research area is the decision-making process. In other words, the comprehension of how companies decide about outsourcing their IT operations is relevant from research point of view. Therefore, the objective of this study is to understand the decision-making process used by Brazilian companies when outsourcing their IT operations. An analysis of the literature that refers to this subject showed that six aspects are usually considered by companies on the evaluation of IT outsourcing service alternatives. This research verified how these six aspects are considered by Brazilian companies on IT outsourcing decisions. The survey showed that Brazilian companies consider all the six aspects, but each of them has a different level of importance. The research also grouped the aspects according to their level of importance and interdependency, using factorial analysis to understand the logic behind IT outsourcing decision process. (C) 2009 Elsevier B.V. All rights reserved.
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Os ??rg??os da Administra????o P??blica Federal (APF) ter??o maior ??xito no alcance de seus objetivos estrat??gicos, investindo na implanta????o de um modelo de gest??o estrat??gica, adaptado para o ambiente de governo, mantendo o alinhamento estrat??gico com os ??rg??os normativos e de controle. Este artigo tem como objetivo apresentar um modelo de gest??o estrat??gica, adaptado a partir das perspectivas do Balanced Scorecard (BSC) desenvolvido pelos professores da Harvard Business School, Robert Kaplan e David Norton, em 1992, para ser utilizado pelos ??rg??os da APF; tal modelo mant??m um alinhamento estrat??gico organizacional com as recomenda????es do Tribunal de Contas da Uni??o (TCU). O modelo ir?? permitir a gest??o estrat??gica a partir da identifica????o dos objetivos estrat??gicos, metas, indicadores e a????es referentes ??s perspectivas do Balanced Scorecard, o que permitir?? o equil??brio entre os indicadores de efici??ncia no acompanhamento das metas de cada ??rg??o da APF, colaborando para uma gest??o estrat??gica integrada, que venha a modernizar a gest??o p??blica, agilizando as tomadas de decis??es e a troca de informa????es.
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Tese de Doutoramento, Ciências do Mar (Ecologia Marinha), 26 de Novembro de 2013, Universidade dos Açores.
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This paper addresses a gap in the literature concerning the management of Intellectual Capital (IC) in a port, which is a network of independent organizations that act together in the provision of a set of services. As far as the authors are aware, this type of empirical context has been unexplored when regarding knowledge management or IC creation/destruction. Indeed, most research in IC still focus on individual firms, despite the more recent interest placed on the analysis of macro-level units such as regions or nations. In this study, we conceptualise the port as meta-organisation, which has the generic goal of economic development, both for itself and for the region where it is located. It provides us with a unique environment due to its complexity as an “organisation” composed by several organisations, connected by interdependency relationships and, typically, with no formal hierarchy. Accordingly, actors’ interests are not always aligned and in some situations their individual interests can be misaligned with the collective goals of the port. Moreover, besides having their own interests, port actors also have different sources of influence and different levels of power, which can impact on the port’s Collective Intellectual Capital (CIC). Consequently, the management of the port’s CIC can be crucial in order for its goals to be met. With this paper we intend to discuss how the network coordinator (the port authority) manages those complex relations of interest and power in order to develop collaboration and mitigate conflict, thus creating collective intellectual assets or avoiding intellectual liabilities that may emerge for the whole port. The fact that we are studying complex and dynamic processes, about which there is a lack of understanding, in a complex and atypical organisation, leads us to consider the case study as an appropriate method of research. Evidence presented in this study results from preliminary interviews and also from document analysis. Findings suggest that alignment of interests and actions, at both dyadic and networking levels, is critical to develop a context of collaboration/cooperation within the port community and, accordingly, the port coordinator should make use of different types of power in order to ensure that port’s goals are achieved.
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Abstract The investigation of the web of relationships between the different elements of the immune system has proven instrumental to better understand this complex biological system. This is particularly true in the case of the interactions between B and T lymphocytes, both during cellular development and at the stage of cellular effectors functions. The understanding of the B–T cells interdependency and the possibility to manipulate this relationship may be directly applicable to situations where immunity is deficient, as is the case of cancer or immune suppression after radio and chemotherapy. The work presented here started with the development of a novel and accurate tool to directly assess the diversity of the cellular repertoire (Chapter III). Contractions of T cell receptor diversity have been related with a deficient immune status. This method uses gene chips platforms where nucleic acids coding for lymphocyte receptors are hybridized and is based on the fact that the frequency of hybridization of nucleic acids to the oligonucleotides on a gene chip varies in direct proportion to diversity. Subsequently, and using this new method and other techniques of cell quantification I examined, in an animal model, the role that polyclonal B cells and immunoglobulin exert upon T cell development in the thymus, specifically on the acquisition of a broader repertoire diversity by the T cell receptors (Chapter IV and V). The hypothesis tested was if the presence of more diverse peptides in the thymus, namely polyclonal immunoglobulin, would induce the generation of more diverse T cells precursors. The results obtained demonstrated that the diversity of the T cell compartment is increased by the presence of polyclonal immunoglobulin. Polyclonal immunoglobulin, and particularly the Fab fragments of the molecule, represent the most diverse self-molecules in the body and its peptides are presented by antigen presenting cells to precursor T cells in the thymus during its development. This probably contributes significantly to the generation of receptor diversity. Furthermore, we also demonstrated that a more diverse repertoire of T lymphocytes is associated with a more effective and robust T cell immune function in vivo, as mice with a more diverse T cell receptors reject minor histocompatiblility discordant skin grafts faster than mice with a shrunken T cell receptor repertoire (Chapter V). We believe that a broader T cell receptor diversity allows a more efficient recognition and rejection of a higher range of external and internal aggressions. In this work it is demonstrated that a reduction of TCR diversity by thymectomy in wild type mice significantly increased survival of H-Y incompatible skin grafts, indicating decrease on T cell function. In addiction reconstitution of T-cell diversity in mice with a decreased T cell repertoire diversity with immunoglobulin Fab fragments, lead to a increase on TCR diversity and to a significantly decreased survival of the skin grafts (Chapter V). These results strongly suggest that increases on T cell repertoire diversity contribute to improvement of T cell function. Our results may have important implications on therapy and immune reconstitution in the context of AIDS, cancer, autoimmunity and post myeloablative treatments. Based on the previous results, we tested the clinical hypothesis that patients with haematological malignancies subjected to stem cell transplantation who recovered a robust immune system would have a better survival compared to patients who did not recover such a robust immune system. This study was undertaken by the examination of the progression and overall survival of 42 patients with mantle cell non-Hodgkin lymphoma receiving autologous hematopoietic stem cell transplantation (Chapter VI). The results obtained show that patients who recovered higher numbers of lymphocytes soon after autologous transplantation had a statistically significantly longer progression free and overall survivals. These results demonstrate the positive impact that a more robust immune system reconstitution after stem cell transplantation may have upon the survival of patients with haematological malignancies. In a similar clinical research framework, this dissertation also includes the study of the impact of recovering normal serum levels of polyclonal immunoglobulin on the survival of patients with another B cell haematological malignancy, multiple myeloma, after autologous stem cell transplantation (Chapter VII). The relapse free survival of the 110 patients with multiple myeloma analysed was associated with their ability to recover normal serum levels of the polyclonal compartment of immunoglobulin. These results suggest again the important effect of polyclonal immunoglobulin for the (re)generation of the immune competence. We also studied the impact of a robust immunity for the response to treatment with the antibody anti CD20, rituximab, in patients with non- Hodgkin’s lymphoma (NHL) (Chapter VIII). Patients with higher absolute counts of CD4+ T lymphocytes respond better (in terms of longer progression free survival) to rituximab compared to patients with lower number of CD4+ T lymphocytes. These observations highlight again the fact that a competent immune system is required for the clinical benefit of rituximab therapy in NHL patients. In conclusion, the work presented in this dissertation demonstrates, for the first time, that diverse B cells and polyclonal immunoglobulin promote T cell diversification in the thymus and improve T lymphocyte function. Also, it shows that in the setting of immune reconstitution, as after autologous stem cell transplantation for mantle cell lymphoma and in the setting of immune therapy for NHL, the absolute lymphocyte counts are an independent factor predicting progression free and overall survival. These results can have an important application in the clinical practice since the majority of the current treatments for cancer are immunosuppressive and implicate a subsequent immune recovery. Also, the effects of a number of antineoplastic treatments, including biological agents, depend on the immune system activity. In this way, studies similar to the ones presented here, where methods to improve the immune reconstitution are examined, may prove to be instrumental for a better understanding of the immune system and to guide more efficient treatment options and the design of future clinical trials. Resumo O estudo da rede de inter-relações entre os diversos elementos do sistema immune tem-se mostrado um instrumento essencial para uma melhor compreensão deste complexo sistema biológico. Tal é particularmente verdade no caso das interacções entre os linfócitos B e T, quer durante o desenvolvimento celular, quer ao nível das funções celulares efectoras. A compreensão da interdependência entre linfócitos B e T e a possibilidade de manipular esta relação pode ser directamente aplicável a situações em que a imunidade está deficiente, como é o caso das doenças neoplásicas ou da imunossupressão após radio ou quimioterapia. O trabalho apresentado nesta dissertação iniciou-se com o desenvolvimento de um novo método laboratorial para medir directamente a diversidade do reportório celular (Capítulo III). Reduções da diversidade do reportório dos receptores de células T têm sido relacionadas com um estado de imunodeficiência. O método desenvolvido utiliza “gene chips”, aos quais hibridizam os ácidos nucleicos codificantes das cadeias proteicas dos receptores linfocitários. A diversidade é calculada com base na frequência de hibridização do ácido nucleico da amostra aos oligonucleótidos presentes no “gene chip”. De seguida, e utilizando este novo método e outras técnicas de quantificação celular examinei, num modelo animal, o papel que as células policlonais B e a imunoglobulina exercem sobre o desenvolvimento linfocitário T no timo, especificamente na aquisição de um reportório diverso de receptores T (Capítulos IV e V). Testei, então, a hipótese de que a presença no timo de péptidos mais diversos, como a imunoglobulna policlonal, induzisse a génese de precursores T mais diversos. Demonstrámos que a diversidade do compartimento T é aumentado pela presença de imunoglobulina policlonal. A imunoglobulina policlonal, e particularmente os fragmentos Fab desta molécula, representam as moléculas autólogas mais diversas presentes nos organismos vertebrados. Estes péptidos são apresentados por células apresentadoras de antigénio às células precursoras T no timo, durante o desenvolvimento celular T. Tal, provavelmente, contribui para a génese da diversidade dos receptores. Também demonstrámos que a presença de um reportório mais diverso de linfócitos T se associa a um incremento da função imunológica T in vivo. Uma diversidade de receptores T mais extensa parece permitir um reconhecimento e rejeição mais eficientes de um maior número de agressores internos e externos. Demonstrámos que ratinhos com receptores de células T (RCT) com maior diversidade rejeitam transplantes cutâneos discordantes para antigénios minor de histocompatibilidade mais rapidamente do que ratinhos com um menor reportório T (Capítulo V). Por outro lado, uma redução da diversidade do RCT, causada por timectomia de ratinhos de estirpes selvagens, mostrou aumentar significativamente a sobrevivência de transplantes cutâneos incompatíveis para o antigénio H-Y (antigénio minor de histocompatibilidade), indicando uma diminuição da função linfocitária T. Além disso, a reconstituição da diversidade dos linfócitos T em ratinhos com uma diversidade de reportório T diminuída, induzida pela administração de fragmentos Fab de imunoglobulina, conduz a um aumento da diversidade dos RCT e a uma diminuição significativa da sobrevivência dos enxertos cutâneos (Capítulo V). Estes resultados sugerem que o aumento do reportório de células T contribui para uma melhoria das funções celulares T e poderão ter implicações importantes na terapêutica e reconstitutição imunológica em contexto de SIDA, neoplasias, autoimunidade e após tratamentos mieloablativos. Baseado nos resultados anteriores, decidimos testar a hipótese clínica de que doentes com neoplasias hematológicas sujeitos a transplantação de precursores hematopoiéticos e com recuperação imunológica precoce após transplante teriam uma sobrevivência mais longa do que doentes que não recuperassem tão bem a sua imunidade. Analisámos a sobrevivência global e sobrevivência sem doença de 42 doentes com linfoma não Hodgkin de células do manto sujeitos a transplante autólogo de precursores hematopoiéticos (Capítulo VI). Os resultados obtidos mostraram que os doentes que recuperaram contagens mais elevadas de linfócitos imediatamente após o transplante autólogo, apresentaram uma sobrevivência global e sem progressão mais longa do que doentes que não recuperaram contagens linfocitárias tão precocemente. Estes resultados demonstram o efeito positivo de uma reconstitutição imunológica robusta após transplante de presursores hematopoiéticos, sobre a sobrevivência de doentes com neoplasias hematológicas. Do mesmo modo, estudámos o efeito que a recuperação de níveis séricos normais de imunoglobulina policlonal tem na sobrevivência de doentes com outras neoplasias hematológicas de linfócitos B, como o mieloma múltiplo,após transplante autólogo de precursos hematopoiéticos (Capítulo VII). A sobrevivência livre de doença dos 110 doentes com mieloma múltiplo analizados está associada com a sua capacidade de recuperar níveis séricos normais do compartmento policlonal de imunoglobulina. Estes resultados pioneiros indicam a importância da imunoglobulina policlonal para a génese de competência imunológica. Também estudámos o impacto de um sistema imunitário eficiente sobre a resposta ao tratamento com o anticorpo anti CD20, ituximab, em doentes com linfoma não Hodgkin (LNH) (Capítulo VIII). Os resultados mostram que doentes com valores mais elevados de linfócitos T CD4+ respondem melhor (em termos de maior sobrevida livre de doença) ao rituximab, do que doentes com valores mais baixos. Estas observações ilustram a necessidade de um sistema imunitário competente para o benefício clínico da terapêutica com rituximab em doentes com LNH. Em conclusão, o trabalho apresentado nesta dissertação demonstra que as células B e a imunoglobulina policlonal promovem a diversidade das células T no timo e melhoram a função linfocitária T periférica. Concomitantemente, também demonstrámos que, no contexto de reconstituição imune, por exemplo, após transplante autólogo de precursores hematopoiéticos em doentes com linfomas de células do manto, o número absoluto de linfócitos é uma factor independente da sobrevivência. Os resultados demonstram, também, a importância dos valores de linfocitos T na resposta ao tratamento com rituximab no caso de doentes com LNH. O mesmo princípio se prova pelo facto de que doentes com mieloma múltiplo sujeitos a transplante autólogo de precursores hematopoiéticos que recuperam valores normais séricos de imunoglobulinas policlonais, terem melhores taxas de resposta em comparação com doentes que não recuperam valores normais de imunoglobulinas policlonais. Estes resultados podem ter importantes aplicações na prática clínica dado que a maioria dos tratamentos de doenças neoplásicas implica imunossupressão e, subsequente, recuperação imunológica. Estes estudos podem ser um instrumento fundamental para uma melhor compreensão do sistema imune e guiar uma escolha mais eficiente de opções terapêuticas bem como contribuir para a concepção de futuros estudos clínicos.
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A perfuração é uma das operações envolvidas no desmonte de rocha com explosivos. A forma como esta operação é executada é determinante para o sucesso do desmonte. Quando é realizada correctamente o desmonte produz superfícies limpas com o mínimo de sobrescavação e perturbação. A selecção das ferramentas de perfuração é um dos factores preponderantes para os custos do desmonte de maciços rochosos. A forma como a perfuração é executada é determinante para a boa fragmentação do maciço rochoso. Este estudo irá centrar‐se na perfurabilidade do maciço, linearidade dos furos e desenvolvimento de metodologias do ciclo de perfuração. O objectivo geral deste trabalho é demonstrar a interdependência entre os parâmetros geológicos e geotécnicos do maciço rochoso e as tecnologias de perfuração de forma a optimizar tanto técnica como economicamente. O controlo geomecânico do desmonte do maciço rochoso através de uma perfuração alinhada é salientado com o intuito de uma abordagem de geoengenharia integrada nos maciços rochosos.
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Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em História Moderna e dos Descobrimentos