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Gambaro, Sabrina Eliana. "Ruolo dei citocromi P450 cerebrali nell’ossidazione della bilirubina: inducibilità ed attività." Doctoral thesis, Università degli studi di Trieste, 2014. http://hdl.handle.net/10077/10116.
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2012/2013Abstract Hyperbilirubinemia is the most common clinical diagnosis during neona- tal life. The neonatal jaundice may be physiological without any clinical consequence, or can lead to an acute form of bilirubin en- cephalopathy with minimal neurological damage, or to more severe and dangerous condition called kernicterus (permanent neurological sequelae). The Gunn rat is one of the models in which bilirubin encephalopathy was studied. It was shown that jaundiced newborn animals display an hepatic compensatory mechanism for the incapacity to eliminate bilirubin (Ugt1A1 mutant enzyme) by upregulation of cyotochrome P450 enzymes (Cyp) 1A1 and 1A2 compared with their not jaun- diced littermates. In addition, their expression in brain was selec- tively induced (cortex higher and early vs. cerebellum lower and late induction) by sudden increase of bilirubin content. Cyotochrome P450 enzymes are the main enzymes involved in the detoxification of drug and endogenous compounds. In liver their role in bilirubin oxidation has been deeply demonstrated. In brain, there are many works that analyzed Cyps expression and induction, but their role in bilirubin oxidation has never been evaluated till now. This thesis focused in; 1) analyze the inducibility of Cyps enzymes, by a known inducer, βNF in cortex and cerebellum astrocytes; 2) Select the optimal conditions to induce specifically each of them; 3) analyze their activity and 4) evaluate their capacity to oxidize bilirubin; 5) Last but not least, assess the protective effect of Cyps induction by challenging the cells with high concentrations of bilirubin.We demonstrated that astrocytes Cyps were inducible (both mRNA and activity) by βNF and this induction varies depending on the brain region and among the Cyps. To explain the differences we hypoth- esized the presence of: i) a different protein isoforms (discarded for Cyp1A1) ii) different maturation stage of astrocytes in the two brain regions (P2 rats: Cll is less developed than Cx), iii) differential regu- latory mechanisms. Our work showed that in Cx astrocytes Cyp1A1 induction (mRNA and activity) was an early event (6h), requiring low concentration of the drug, making this approach theoretically possible in vivo. On the other hand, to reach the higher levels of Cyp1A1 (mRNA and activ- ity) in Cll we needed 24h. In both cases Cyp1A1 was able to oxidize bilirubin producing an increase in viability only after TCB addition. The Cyp1A2 was the major catalyst of bilirubin degradation (with- out the need of TCB), but its modulation was more difficult to be achieved. In addition, while Cyp1A2 modulation increased bilirubin oxidation in cortex (also reflected in an increment in viability), in cerebellum we noticed a slight reduction in bilirubin clearance (no improvements in viability). All this data could lead to the basis of the cerebellum susceptibility to UCB. The observation that the TCB addition in Cyp1A1 astrocytes increases bilirubin oxidation and via- bility suggest the possibility to induce Cll resistance toward bilirubin neurotoxicity by Cyps modulation and uncoupling. --------------------------------------------- Riassunto Una delle condizioni neonatali pi`u comuni `e l’ittero. Esso rappresenta l’aumento fisiologico della bilirubina nel sangue e tessuti. Tuttavia esso pu`o divenire una condizione patologica (encefalopatia da biliru- bina), caratterizzata da un danno neurologico minimo, o condurre a una condizione severa e pericolosa per il neonato chiamata kernit- tero (danni permanenti), in caso di una esposizione prolungata ad alti livelli del pigmento. Attualmente, la patologia da iperbilirubinemia rappresenta la principale causa di riammissione in ospedale nel primo mese di vita. Per il danno neurologico da bilirubina esiste un modello animale, il ratto Gunn, che presenta la stessa mutazione genica dei pazienti Crigler-Najjar I. Come nella condizione umana, esso manca della uridin di fosfo glucuronisil tranferasi 1a1 (Ugt1A1), enzima epatico deputato alla coniugazione della bilirubina. Tuttavia l’animale ri- esce a compensare la mancanza mantenendo bassi i livelli serici di bilirubina, grazie ad una incrementata attivit`a delle citocromo P450 mono-ossigenasi epatiche (Cyps, Cyp1A1 and Cyp1A2). Tali enzimi riducono la concentrazione del pigmento attraverso la sua ossidazione. ` E stato supposto che questo meccanismo possa essere alla base anche della capacit`a di specifiche aree del cervello (cortex e collicoli superiori, vs. i danneggiati cervelletto, ippocampo e collicoli inferiori) di ridurre la concentrazione del pigmento, limitando/impedendo il danno neu- rologico associato. Sebbene il loro ruolo, i meccanismi ed i prodotti della loro attivit`a di clearance della bilirubina siano stati ampiamente dimostrati in fegato, in cervello non sono ancora disponibili evidenze funzionali della loro capacit`a di ossidare la bilirubina. L’obiettivo di questa tesi `e stato di analizzare 1) la modulazione delle Cyps cerebrali (brain Cyp: bCyp) utilizzando un noto induttore, βNF; 2) selezionare le condizione ottimali per una induzione selettiva di cias- cuna bCyp; 3) allo scopo di valutare la loro attivit`a (EROD/MROD);4) e la capacit`a specifica di ossidare bilirubina; 5) conferendo pro- tezione (aumento vitalit`a) alle culture primarie di astrociti (da cortex e cervelletto) esposte a dosi tossiche di bilirubina. Questo studio ha dimostrato la inducibilit`a delle bCyps (mRNA e attivit`a) tramite βNF. Abbiamo evidenziato una modulazione dipen- dente della regione cerebrale da cui sono state prodotte le cellule, in aggiunta ad un comportamento differenziale delle Cyps tra loro. Pos- sibili spiegazioni possono essere: i) la presenza di diverse isoforme tra le regioni (ipotesi scartata in seguito ad analisi tramite western blot); ii) diversa presenza delle vie di segnalazione alla base dei meccanismi di modulazione, o, iii) una diversa risposta dovuta al diverso stadio sviluppo degli astrociti preparati dalle due regioni (ratti P2: il Cll `e meno sviluppato del Cx). Inoltre, abbiamo documentato una precoce (6h) inducibilit`a della Cyp1A1 nei astrociti dal Cx, che inoltre necessit`a di minori concen- trazioni del principio. Tali caratteristiche suggeriscono che la Cyp1A1 sia pi`u facilmente modulabile in vivo. Tuttavia, per ottenere una buona modulazione nel cervelletto (regione pi`u sensibile al danno), bisogna mantenere la concentrazione dell’ induttore per un tempo lungo (24h). In entrambe le regioni, un incremento significativo della capacit`a di ossidare bilirubina, migliorando la vitalit`a delle cellule, `e stato ottenuto solo dopo il co-trattamento con TCB (disaccoppia- mento). La Cyp1A2 `e stata significativamente modulata solo negli astrociti da Cx (24h), in cui abbiamo evidenziato un chiara capacit`a dell’enzima di ossidare la bilirubina e migliorare la vitalit`a in assenza di TCB. I risultati ottenuti permettono di comprendere la suscettibilit`a differenziale (tra regioni del cervello) tipica di questa patologia. La capacit`a di indurre Cyp1A1 e renderli pronti a ossidare la bilirubina nei astrociti da Cll (regione pi`u danneggiata) e Cyp1A1/Cyp1A2 in Cx e oltre migliorando la viabilit`a di questi suggeriscono la possibilit`a di conferire resistenza a la tossicit`a da bilirubina.
XXVI Ciclo
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Rea, Alexander David. "Fast tip-tilt correction at the MROI and beyond." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708940.
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Majer, Florian. "Molekularbiologische und biochemische Charakterisierung der Lantibiotika-Biosyntheseenzyme EpiD und MrsD /." [S.l. : s.n.], 2002. http://www.gbv.de/dms/bs/toc/356619915.pdf.
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Mroz, Magda [Verfasser]. "Time-varying copula models for financial time series / Magda Mroz." Ulm : Universität Ulm. Fakultät für Mathematik und Wirtschaftswissenschaften, 2012. http://d-nb.info/1027341578/34.
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Al-kaabi, Hamad A. "Airlines' maintenance, repair and overhaul (MRO) configurations." Thesis, Cardiff University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437225.
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Liu, Fu-Chau. "Evaluation of effective MDTD/MRTD for FLIR from PREOS92 measurement data." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 1996. http://handle.dtic.mil/100.2/ADA316563.
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Thesis (M.S. in Applied Physics (Electro-Optics)) Naval Postgraduate School, June 1996.Thesis advisor(s): Alfred W. Cooper, Donald L. Walters. "June 1996." Includes bibliographical references. Also available online.
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Ma, Xing. "Analysis of the role of MreC and MreD in Staphylococcus aureus." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/16060/.
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Bergkvist, Erik, and Tommy Sabbagh. "Smart Future Solutions for Maintenance of Aircraft : Enhancing Aircraft Maintenance at Saab AB." Thesis, Linköpings universitet, Industriell Produktion, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-176561.
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This master thesis has the purpose to analyse and identify smart efficient future solutions within the Maintenance, Repair and Overhaul (MRO) process for aircraft. The efficiency solutions, in form of new technologies and tools, should present a foundation that MRO suppliers can continue to develop to enhance and streamline their maintenance processes. The project was performed as a case study at the aerospace and defense company Saab AB in Linköping, where the company's MRO process was investigated. Through identifying possibilities and alternative technologies available today and in the near future, one continues to have a competitive and future-proof position in the market. Through an own constructed course of action influenced from established methods, the thesis' purpose and aim was attained. The method was based on authentic approaches for case studies but also inspired by the so-called "Requirement Engineering". The combination of the methods resulted in a precise focus on the relevant subjects, together with a clear structure of the requirements on the technologies to reach a successful implementation. Through a detailed data collection comprised of study visits, interviews, literature studies, market analyses, and document reviews, multiple relevant technologies and requirement-lists for utilization were identified. To concretize the use and potential improvements with the technologies, the project had the objective to develop a demonstrator with one of the technologies presented. The demonstrator should focus on minimizing the use of paper, which is a common problem among many market actors today. The most promising technology was considered to be a tablet application with an accommodated application. The selection of the tablet solution was based on the motivation that it is a well-established technology and a favorable first step from paperwork. To conclude this master thesis, a tablet application was developed in Novacura Flow Studio, where the majority of the identified requirements were fulfilled. Beyond the demonstrator, an introduction and analysis of technologies, such as AR-glasses, voice guidance, additive manufacturing, and a digital twin, was presented.
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Freidl, Marco. "MRO-Modelle in der Luftfahrtindustrie Strategische Handlungsoptionen für Airlines /." St. Gallen, 2007. http://www.biblio.unisg.ch/org/biblio/edoc.nsf/wwwDisplayIdentifier/04602850001/$FILE/04602850001.pdf.
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Poon, Arthur Wai Keong 1979. "Software agents : an application to the airline MRO industry." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/17783.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2004.Includes bibliographical references (p. 115-118).
Poor management of aircraft spare parts, human-related maintenance errors and the lack of coordinated decision-making in maintenance scheduling are some of the problems plaguing the airline MRO industry. Airlines, independent MRO providers and government agencies, particularly the Federal Aviation Administration have identified inefficiencies in MRO operations as a barrier to the realization of a safer and more effective air transportation system. The National Airspace System is slowly beginning to address this problem and one of its initiatives involves the gradual adoption of agent-based solutions and ontologies to automate some of the business processes in MRO depots. Agents and automated processes are ideal choices for making sense of ontologies and are key components in the next generation Semantic Web. The focus lies with improving business logic and practices of air carriers' MRO activities using software agent principles. This thesis proposes agent architectures for aircraft inspections, repairs and supply chain management of aircraft replacement parts and discusses the resulting implications of using agents as a decision-making tool for aircraft maintenance and repair in commercial airlines.
by Arthur Wai Keong Poon.
S.M.
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Tavares, Dayana Virgínia Gonçalves. "Metodologia Lean aplicada a um ambiente MRO: componentes aeronáuticos." Master's thesis, Universidade da Beira Interior, 2011. http://hdl.handle.net/10400.6/2051.
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O objectivo desta dissertação é analisar as ferramentas da metodologia Lean, por um lado, e por outro, perceber como se procede à aplicação das mesmas no ambiente de manutenção aeronáutica num operador de linha aérea.
De forma a alcançar o objectivo realizou-se um caso de estudo na empresa TAP, em particular, de um projecto de melhoria denominado “Planeamento de Prioridades”. A TAP é a companhia aérea de bandeira nacional líder de mercado que presta serviços na indústria aeronáutica. Para o efeito acompanhou-se o trabalho da Equipa de Melhoria Contínua durante 8 meses.
Com este caso de estudo concluiu-se, entre outros aspectos, que é importante ter um apoio forte da gestão de topo para uma implementação eficaz, os colaboradores ficam mais conscientes de todas as etapas do Processo global, a metodologia Lean é uma mudança cultural que permite eliminar desperdícios em processos. Também se concluiu que as mudanças requeridas encontram dificuldades, como contabilização dos ganhos, o facto de não ser uma metodologia intuitiva, a qual no início, encontrar resistência por parte de colaboradores que temem perder o seu trabalho.The purpose of this dissertation is to analyze, on one hand, the tools applicable to the Lean Techniques, and on the other one, see how it results on aircraft maintenance of an airline operator. In order to achieve the above goal, a case study was assessed at the Portuguese flag carrier TAP, in particular, an improvement project entitled "Planning Priorities." TAP is the national flag airline, a market leader that provides services in the aerospace industry. To this end, the work of related to this dissertation took followed the Continuous Improvement Team for 8 months. This case-study allowed to conclude, among several aspects, it is important to have strong support from the top management for an effective implementation; employees are more aware of every step of the overall process; the Lean Techniques imply a cultural change that allows to eliminate waste in processes. It also concluded that the changes required have encountered difficulties, such as, the need to accounting earnings; the fact that it is not an intuitive approach the employees tend to resist because they feel that may lose their jobs.
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Westerberg, Per-Anton, Åsa Tivesten, Magnus Karlsson, Dan Mellström, Orwoll Eric, Claes Ohlsson, Tobias Larsson, Torbjörn Linde, and Östen Ljunggren. "Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs)." Uppsala universitet, Njurmedicin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-188146.
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Background: Fibroblast growth factor 23 (FGF23) is the earliest marker of disturbed mineral metabolism as renal function decreases. Its serum levels are associated with mortality in dialysis patients, persons with chronic kidney disease (CKD) and prevalent cardiovascular disease (CVD), and it is associated with atherosclerosis, endothelial dysfunction and left ventricular hypertrophy in the general population. The primary aim of this study is to examine the association between FGF23 and mortality, in relation to renal function in the community. A secondary aim is to examine the association between FGF23 and CVD related death. Methods: The population-based cohort of MrOS Sweden included 3014 men (age 69-81 years). At inclusion intact FGF23, intact parathyroid hormone (PTH), 25 hydroxyl vitamin D (25D), calcium and phosphate were measured. Mortality data were collected after an average of 4.5 years follow-up. 352 deaths occurred, 132 of CVD. Association between FGF23 and mortality was analyzed in quartiles of FGF23. Kaplan-Meier curves and Log-rank test were used to examine time to events. Cox proportional hazards regression was used to examine the association between FGF23, in quartiles and as a continuous variable, with mortality. The associations were also analyzed in the sub-cohort with estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m(2). Results: There was no association between FGF23 and all-cause mortality, Hazard ratio (HR) 95% confidence interval (CI): 1.02 (0.89-1.17). For CVD death the HR (95% CI) was 1.26 (0.99 - 1.59)/(1-SD) increase in log(10) FGF23 after adjustment for eGFR, and other confounders. In the sub-cohort with eGFR > 60 ml/min/1.73 m(2) the HR (95% CI) for CVD death was 55% (13-111)/(1-SD) increase in log(10) FGF23. Conclusions: FGF23 is not associated with mortality of all-cause in elderly community living men, but there is a weak association with CVD death, even after adjustment for eGFR and the other confounders. The association with CVD death is noticeable only in the sub-cohort with preserved renal function.
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Slovak, Peter Michael. "Characterisation of the mre and mrd loci of Rhodobacter sphaeroides." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414270.
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Campos, Joaquim Manuel de Oliveira. "A procura da melhoria da eficiência operacional em ambiente MRO." Master's thesis, Instituto Superior de Economia e Gestão, 2015. http://hdl.handle.net/10400.5/10660.
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Mestrado em Gestão e Estratégia IndustrialEste trabalho procura respostas relacionadas com a perseguição de níveis de excelência operacional por parte das organizações visto que nos dias em que se vive hoje, também as organizações passam por recessões económicas e por isso são obrigadas a reinventarem-se, procurarem e implementarem ações para melhorarem a eficiência das suas operações, e assim apresentarem vantagens competitivas relativamente aos seus adversários. Da revisão da literatura surgiram várias abordagens que se procura investigar como flexibilidade estratégica e capacidades das empresas e ainda abordagens relacionadas com a metodologia LEAN e indicadores de desempenho. Este trabalho ilustra dois projetos que procuram a melhoria da eficiência operacional por parte de uma empresa que opera em ambiente MRO. Um corporativo que é transversal a todas as áreas da empresa, e outro local, focado na operação de MRO de componentes aeronáuticos que vai para além das ações corporativas. Verifica-se que o resultado da ações locais ficaram aquém do esperado, mantendo a dificuldade da gestão da expectativa gerada no cliente, apesar do esforço e vontade dos gestores no desenvolvimento e implementação de ações na procura de melhorar a eficiência operacional quando comparados com o resultado das às ações corporativas. Ou seja, os gestores de operações que se deparem com o problema de terem de melhorar a eficiência operacional de uma qualquer operação que estejam envolvidos têm uma probabilidade maior de sucesso se desenvolverem e implementarem projetos corporativos que envolvam o maior número de colaboradores e que seja transversal a toda a empresa.
This work it aims to find answers regarding the organizations in the pursuit of the operational efficiency by the organizations. In the days that we living today, the organizations also have to struggle with the economic resection due to economics cycles and global competitiveness and therefore are enforced to reinvent themselves in searching for and in implementing actions to improving the efficiency of its operations and so achieve competitive advantage against the competition. There is different approaches in literature review that can be explored such as strategic flexibility and companies' capacity and approaches linked with lean methodology and KPI's. This work refers two projects, one corporate and other local. Both projects pursuing the operational efficiency improvement from a MRO company. The corporate project cover all areas off the company, and other local focusing on MRO aeronautic components that goes beyond the corporate actions. It appears that the outcome of the local actions, was less than expected, maintaining difficult the client expectation management, in spite of considerable efforts on the part of the managers in implementation and developing actions for improving the operational efficiency when compared to the outcome of the corporate actions. In other words, the operations managers that have operational problems to solve from any operation that they are involve, they will probably go get better results if implement and developed corporate actions, that involve the majority of workers and that cover the majority of the company departments.
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Bordignon, Gerson. "E-procurement associado a MRO: o caso Caixa Econômica Federal." reponame:Repositório Institucional do FGV, 2003. http://hdl.handle.net/10438/3769.
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Previous issue date: 2003The evolution of Information Technology (IT) - principally the Internet - from the academic realm to the business arena has generated discussions concerning the impact of this process on existing business models. The Brazilian government has been working to adjust its legal framework in order to take advantage of the benefits the new business environment offers the public sector. The primary objective of this study is to identify the benefits accruing to the Caixa Econômica Federal, in terms of improved efficiency, from the implementation of its online shopping site, MRO (maintenance, repair and operation). Using a simplified case study methodology, an analysis of the strategic importance of the implementation of the Caixa Econômica Federal' 5 shopping site is provided, specifically focused on how the relevant technological, organizational, and cultural' aspects have influenced the efficiency of the institution's productive processes. While the results obtained are significant with respect to investmentrecovery time, and promising in terms of the possibilities they offer for reducing the institution's administrative costs, of greater relevance is the site's potential as a mechanism for adding value to the bank's financiai performance. In this context, the Caixa Econômica Federal's challenge is to wed the market opportunities arising from the expertise that has been acquired to the idle capacity generated by productivity gains, and, in this way, to develop a product that provides vast revenue generating potential.
A evolução da Tecnologia da Informação (TI) - mormente da Internet -, deslocando-se do meio acadêmico para a área de negócios, tem gerado discussões sobre seu impacto em modelos de negócios existentes. O Governo Brasileiro vem adequando a sua base legal, de forma a aproveitar os benefícios que esse novo ambiente de negócios pode trazer à estrutura pública. Este trabalho tem como principal objetivo identificar os benefícios alcançados pela Caixa Econômica Federal, no que se refere a melhorias na sua eficiência, ao implantar o seu site de compras MRO (Manutenção, Reparo e Operação). Através de metodologia de estudo de caso simples, busca-se analisar a importância estratégica da implantação do site de compras da Caixa Econômica Federal, investigando como as dimensões tecnológica, organizacional e cultural influenciaram a eficiência de seus processos produtivos. Embora os resultados obtidos sejam expressivos em relação ao tempo de recuperação do investimento, e promissores em relação ao potencial de reduzir custos administrativos da empresa, um fator considerado extremamente relevante é que o site tem grande potencial para agregar valor à performance financeira do banco. Neste contexto, a Caixa Econômica Federal deve aliar a oportunidade mercadológica gerada pela expertise desenvolvida, com a ociosidade que se cria com os ganhos de produtividade no processo, formando, assim, um produto com grande capacidade de geração de receita.
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Altabba, Abdulrahman, and Lina Karlsson. "A framework for implementing the VMI model in an MRO partnership." Thesis, Högskolan i Gävle, Avdelningen för Industriell utveckling, IT och Samhällsbyggnad, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-21961.
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Purpose - The purpose of this paper is to investigate the feasibility of implementing the Vendor Managed Inventory (VMI) model in an MRO (maintenance, repair, and operations) partnership, and highlight its potential economic, environmental, and organizational benefits, as well as limitations. Approach - First, a comprehensive literature review was conducted on fields relevant to VMI. Second, empirical data was gathered from a single exploratory case study with Momentum Industrial, and its customer Stora Enso. Semi-structured interviews were used to gather data from the case companies. Findings - Results suggest that VMI results in benefits for the supply chain in general, such as reduced administration and inventory costs, improved service levels, reduced information distortion, and improved relationship among partners. For the particular case of VMI in an MRO partnership, improved service levels can be obtained by a reduced risk of production downtime for the customer. Moreover, the implementation of VMI has potential environmental benefits, such as reduced paper use, and higher transportation fill rate. Limitations of implementing VMI include the difficulty in system integration, and information sharing. Trust could be a potential issue that limits information sharing amongst supply chain partners. Moreover, the difference in organizational cultures and policies of partners should be taken into consideration. Limitations - The study is limited to opinions from one MRO customer in the paper and packaging industry. Even though the questions asked to informants in Momentum and Stora Enso tackled benefits to MRO customers in general, a broader image could have been achieved by interviewing customers from different industries. Moreover, the case companies do not currently adopt VMI in their partnership, so the case study results are based on what they think would be the potential benefits and limitations of implementing VMI in an MRO partnership. Practical Implications - This paper can serve as a guideline for logistics managers who are considering VMI in an MRO partnership specifically, as it provides them with the benefits and limitations associated with VMI. More generally, any company considering VMI can also benefit from the theoretical framework presented.
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Jülg, Peter [Verfasser], and Roland [Akademischer Betreuer] Zengerle. "Microfluidic automation of multiplex mediator probe PCR for leukaemia MRD monitoring." Freiburg : Universität, 2020. http://d-nb.info/121641758X/34.
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Ebling, Thaís. "mRED – um método para a engenharia de requisitos em ambientes de desenvolvimento distribuído de software." Pontifícia Universidade Católica do Rio Grande do Sul, 2009. http://hdl.handle.net/10923/1603.
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Previous issue date: 2009Requirements Engineering (RE) is a software development stage that requires constant communication and collaboration between the stakeholders. Due this collaborative nature, the RE presents several challenges in Distributed Software Development(DSD) environments [DAM02][DAM07][SEN06] - approach where teams often presents geographic dispersion (physical distance), temporal and sociocultural differences (different time-zones, languages and culture) [AUD07]. We can notice the increasing of studies about this phenomenon, aiming to reduce the RE difficulties in DSD environments. One proposal to systematize the RE is the adoption of a reuse approach [CHE07], specifically the Software Product Line (SPL) which supports the requirements reuse of the company's domain [CHA01][LlN07][POH98]. Thus, we present the mRED method that allows the requirements reuse by using SPL in DSD environments, and also we propose a Reuse Policy (based on a DSD literature review) which suggests some tools, techniques and practices specific to distributed environments for each one of the activities of the method. The mRED was evaluated through an experiment between two universities, presenting evidence that its efficiency is higher than the ad hoc RE efficiency in distributed environments.
A Engenharia de Requisitos (ER) é uma etapa do desenvolvimento de software que requer constante comunicação e colaboração entre os stakeholders1. Esta natureza colaborativa faz com que a ER apresente diversos desafios no Desenvolvimento Distribuído de Software (DDS) [DAM02][DAM07][SEN06] – fenômeno onde freqüentemente têm-se um cenário de equipes que possuem dispersão geográfica (distância física), dispersão temporal (diferenças de fuso-horário) e diferenças socioculturais (idioma, costumes, comportamento, etc. ) [AUD07]. Na busca de reduzir as dificuldades da ER dos ambientes distribuídos, diversas propostas surgiram. Uma maneira de sistematizá-la é através da adoção de uma proposta de reutilização [CHE07], mais especificamente da abordagem de Linha de Produto de Software (LPS), a qual enfatiza o reuso de requisitos do domínio da empresa na construção de novos produtos [CHA01][LIN07][POH98].Desta maneira, apresentamos o método mRED2 que possibilita a reutilização de requisitos utilizando LPS em ambientes de DDS, além disto, propomos uma Política de Reutilização que contém sugestões de ferramentas, técnicas e práticas propostas na literatura de DDS, para auxiliar a execução de cada uma das atividades do método. O mRED foi avaliado através de um experimento realizado em parceria entre a Universidade Estadual de Maringá (UEM) e a Pontifícia Universidade Católica do Rio Grande do Sul universidades (PUCRS) e apresentou indícios de que a sua eficiência é maior do que a eficiência do método ad hoc de ER nos ambientes distribuídos.
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Dahlström, Carl, and Emma Giesen. "Mould resistance design for external wood frame wall systems : Simulation and evaluation of wall structures under varying conditions of exposure using the MRD model." Thesis, KTH, Byggnadsteknik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-169744.
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Moisture induced damages to building envelopes can result in microbial growth possibly affecting the health and wellbeing of occupants. Recent failing structures and damaged buildings indicate a lack of tools to estimate risk of mould growth and moisture damage. In this work a so-called mould resistance design (MRD) model has been applied for mapping the risk for mould growth on a number of wood-containing wall structures. The MRD model introduces an engineering approach to moisture safety design in a similar way as for structural design, where load and resistance is compared. The MRD model introduces and quantifies the concepts of climatic exposure and material resistance and compares them through an MRD index. This MRD index incorporates a limit state, which gives the critical dose of exposure for a given resistance to initiate onset of mould growth. Three conceptual wall structures were evaluated and analyzed in terms of MRD index: two wall systems with an air gap and one wall system without. A parametric study investigating the effect of parameter variation on MRD index was conducted. Evaluated parameters were: climate (geographic location), orientation, air changes per hour in the air gap, driving rain penetrating the facade layer, exterior plaster properties and wood type. The simulations were performed using the hygrothermal calculation software WUFI. The results indicate that the wall systems with a ventilated air gap performs better in terms of MRD index i.e. suggests a lower risk of initiation of mould growth than the wall system without air gap. The results of orientation variation show that wall systems perform differently dependent on layering structure. The inherent water sorption properties of the exterior plaster are shown to have a large effect on the results. In addition, uncertainties were found on how to accurately include hydrophobicity as a parameter in the model. The report concludes that geographical location and its specific climate is the most important parameter to consider when designing for moisture safety. The MRD model is recommended to be used in combination with traditional moisture safety evaluation.
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Nguyen, Tuan Kiet. "Efficiency Analysis and Experimental Study of Cooperative Behaviour of Shrimp Farmers Facing Wastewater Pollution in the Mekong River Delta." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/9089.
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Shrimp farming is important to the Vietnamese economy in terms of national income, job creation and poverty alleviation. However, shrimp farming is generally technically inefficient and probably generates too much pollution. To encourage the sustainable development of the Vietnamese shrimp industry, there is a need to improve the productivity of shrimp farms and at the same time to reduce the wastewater pollution generated by shrimp farming. The thesis has two aims: (1) to estimate the efficiency of shrimp farms in the Mekong Delta of Vietnam, with a particular focus on the productivity effects of pollution, and (2) to use experimental economics to investigate policies that could be used to mitigate the wastewater pollution impacting shrimp farms. Overall farmers are found to be inefficient, suggesting farmers are using more inputs than necessary to produce a given output level. Surprisingly, the average extensive (i.e., less capital-intensive) farm is found to be more efficient than the average intensive and semi- intensive (i.e., more capital-intensive) farms. Furthermore, downstream farms are found to be less efficient than upstream farms, suggesting that wastewater pollution influences shrimp farming productivity and results in a negative externality. Evidence from lab-based experiments suggests that the incentives provided by a monitoring and certification agency are not sufficient to promote the full cooperation of shrimp farmers to solve the wastewater pollution problem. However, full cooperation was achieved by providing farmers with an opportunity to communicate. In both cases, self-governance of shrimp farmers was found to be highly effective. The results suggest that community-based management is worthy of further investigation as a possible solution to sustainable development of the shrimp industry in Vietnam. "What we have ignored is what citizens can do and the importance of real involvement of the people involved – versus just having somebody in Washington ... make a rule." Elinor Ostrom (1933-2012)
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Bushyager, Nathan Adam. "Development of models for electrostatically-actuated RF-MEMS interdigitated capacitors using novel FDTD and MRTD approaches." Thesis, Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/15484.
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Hanna, Diana Magdy Fahim [Verfasser]. "Molecular pharmacological analysis of the human MrgD receptor : New insights into signaling / Diana Magdy Fahim Hanna." Bonn : Universitäts- und Landesbibliothek Bonn, 2021. http://d-nb.info/1240761279/34.
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Chedid, Youssef. "Typologie musicale de l’hymnodie syriaque de l’Église Maronite : la tradition du Père Maroun Mrad (Ordre Antonin Maronite)." Thesis, Paris 4, 2015. http://www.theses.fr/2015PA040134.
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Cette thèse se propose de transcrire et analyser dans le but de créer une typologie de l’hymnodie syriaque de l’Église Maronite selon la tradition de l’illustre chantre de l’Ordre Antonin Maronite Père Maroun Mrad. L’Église Maronite, étant une église catholique orientale, elle a conservé et l’union avec l’Église Universelle et son identité et tradition musicale et liturgique. L’objet de mes analyses est l’ensemble des hymnes enregistrées par la voix du Père Maroun Mrad, un des porteurs de la tradition orale au sein de l’Ordre Antonin Maronite. Cet enregistrement est produit par le Père Ivar Schmutz-Schwaller, de l’Université de Cologne, lors de son séjour au Liban en 1972. La méthodologie consiste à produire un diagramme musical de chaque pièce, qui contient toutes les informations utiles à l’analyse. En fait dans ce diagramme on voit l’ensemble de l’échelle utilisée et par conséquent le genre (Zalzalien, Hijaz ou Diatonique). Avec des signes adéquats, on met en relief les degrés d’appui de la pièce (note initiale, teneur, finale temporaire et finale) ainsi que le nombre demouvement (conjoint ou non, ascendant ou descendant) qui les lie. D’après l’ensemble des diagrammes, j’ai choisi la relation finale-teneur comme critère pour la typologie que l’on s’est promis d’établir. En effet, les pièces sont classés en type 1 si leur teneur correspond à leur finale, en type 2 si l’intervalle finale-teneur est une seconde, en type 3 si l’intervallefinale-teneur est une tierce, en type 4 si l’intervalle finale-teneur est une quarte ou en type 5 si cet intervalle est une quinte. Cette typologie sert à classifier ces hymnes pour mieux les repérer et analyser d’autres aspectsThis research wants to transcribe and analyze the Syriac Hymnody of the Maronite Church in order to create a typology. The Maronite Church has conserved its musical and liturgical identity along with its communion with the Universal Church. I based my work on some recording done by Father Ivar Schmutz-Schwaller, from the University of Cologne. In his field trip to Lebanon in 1972, he recorded Father Maroun Mrad, a cantor from the Antonine Maronite Order, while he was singing capella the whole repertoire of the Syriac hymns. The methodology applied here consists in creating a diagram of musical analysis that can summarize the whole piece and simplify the analysis. In fact, each diagram contains all the degrees of the scale and determines its genre (Zalzalian, Hijaz or Diatonic). With the help of some signs, we indicate the basic notes (initial, tenor, temporary ending note and the ending note of the piece) and the number of their movements. With the help of these diagrams, we chose to consider the relation between the “tenor” of the piece and its ending note as criteria for this classification. In fact the pieces that has their tenor equal to their ending note belong to type 1. In the type 2, the interval between the tenor and the ending note is a second, in type 3 a third, in type 4 a fourth and in type 5 a fifth. This typology would help us to better classify these hymns and, furthermore, to analyze other aspects of them
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Ebling, Tha?s. "mRED um m?todo para a engenharia de requisitos em ambientes de desenvolvimento distribu?do de software." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2011. http://tede2.pucrs.br/tede2/handle/tede/5125.
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Previous issue date: 2011-01-21A Engenharia de Requisitos (ER) ? uma etapa do desenvolvimento de software que requer constante comunica??o e colabora??o entre os stakeholders1. Esta natureza colaborativa faz com que a ER apresente diversos desafios no Desenvolvimento Distribu?do de Software (DDS) [DAM02][DAM07][SEN06] fen?meno onde freq?entemente t?m-se um cen?rio de equipes que possuem dispers?o geogr?fica (dist?ncia f?sica), dispers?o temporal (diferen?as de fuso-hor?rio) e diferen?as socioculturais (idioma, costumes, comportamento, etc.) [AUD07]. Na busca de reduzir as dificuldades da ER dos ambientes distribu?dos, diversas propostas surgiram. Uma maneira de sistematiz?-la ? atrav?s da ado??o de uma proposta de reutiliza??o [CHE07], mais especificamente da abordagem de Linha de Produto de Software (LPS), a qual enfatiza o reuso de requisitos do dom?nio da empresa na constru??o de novos produtos [CHA01][LIN07][POH98]. Desta maneira, apresentamos o m?todo mRED2 que possibilita a reutiliza??o de requisitos utilizando LPS em ambientes de DDS, al?m disto, propomos uma Pol?tica de Reutiliza??o que cont?m sugest?es de ferramentas, t?cnicas e pr?ticas propostas na literatura de DDS, para auxiliar a execu??o de cada uma das atividades do m?todo. O mRED foi avaliado atrav?s de um experimento realizado em parceria entre a Universidade Estadual de Maring? (UEM) e a Pontif?cia Universidade Cat?lica do Rio Grande do Sul universidades (PUCRS) e apresentou ind?cios de que a sua efici?ncia ? maior do que a efici?ncia do m?todo ad hoc de ER nos ambientes distribu?dos.
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Doble, Anne Catherine. "Functional analysis of the mrd operon in Salmonella : role in biology and pathogenicity." Thesis, University of Newcastle Upon Tyne, 2012. http://hdl.handle.net/10443/1389.
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Salmonella are major food-borne pathogens responsible for causing a broad spectrum of human disease, ranging from mild gastroenteritis to life-threatening systemic disease. We are interested in analysing the function of the putative mrd operon in Salmonella, whose gene products include PBP2 and RodA; two proteins which are involved in longitudinal cell wall synthesis and essential for rod shapemaintenance in Salmonella. Although PBP2 is fairly well described, surprisingly little is known about the function of RodA or the other mrd operon proteins. This study aimed to characterise the mrd operon, elucidating its contribution to the biology and pathogenicity of Salmonella. Possible links between the structural integrity of the cell wall and the functionality of wall-spanning virulence organelles were also examined. Precise knockout mutations of the mrd operon genes were constructed in Salmonella enterica serovars Typhi and Typhimurium. A range of subsequent phenotypic analyses have revealed that the round-cell ΔpbpA (PBP2) and ΔrodA mutants, though viable and able to stably propagate, are defective in the expression of flagella and the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (T3SS), although the SPI-2 T3SS remains active. These virulence defects were successfully complemented by expressing the major SPI-1 and flagella regulators in trans from inducible promoters. A transposon mutagenesis screen was subsequently developed to search for global regulators of the SPI-1 and motility phenotypes in round-cell mutants. This led to the identification of several candidate regulators, which ongoing work seeks to further analyse. This study has demonstrated that round-cell mrd mutants almost completely down-regulate the expression of key invasion-associated virulence genes, although the cell wall in these mutants remains sufficiently robust to enable the assembly and functioning of wall-spanning multi-protein complexes. Collectively these data provide important insights into both the physiological state of mrd operon mutants, and the function of mrd operon genes.
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Choo, Boon Seh 1979. "Best practices in aircraft engine MRO : a study of commercial and military systems." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/17761.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2004.Includes bibliographical references (p. 109-113).
Maintenance, repair and overhaul (MRO) is a key activity in the lifecycle of an aircraft and its engines. Because of the typically long operational lifetimes expected from these costly assets, MRO is necessary to maintain these systems in a safe and functional condition, so that they can fulfill the operational role that they were designed for. The MRO system can be understood as a complex socio-technical system organized and operated to achieve aircraft availability and operation safety at minimal cost. As a complex socio-technical system, it consists of various layers: The environmental context, organizational structure, management, infrastructure, workers and the technical core. Focusing primarily on infrastructure, management, and manpower, this thesis seeks to identify best practices found within each layer by examining current practices in both commercial and military aircraft engine MRO, as well as surveying potentially useful concepts from related fields to propose how they can be applied to aircraft engine MRO. Among the issues presented are outsourcing, transportation, maintenance scheduling, inventory management, organization culture and human factors.
by Boon Seh Choo.
S.M.
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Biajiz, Mauro. "MRO - UMA ATUALIZAÇÃO DO MODELO DE REPRESENTAÇÃO DE OBJETOS E UMA ABORDAGEM FORMAL." Universidade de São Paulo, 1992. http://www.teses.usp.br/teses/disponiveis/55/55134/tde-02102018-104055/.
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O MR0 (Modelo de Representação de Objetos) é um modelo de bases de dados orientado a objetos, o qual suporta modelagens de aplicações de engenharia. Este trabalho apresenta um formalismo matemático do MR0 cujas principais metas são: validar as definições do modelo; depurar inconsistências do modelo; fornecer uma base para comparação com outros modelos. Durante o processo de formalização, muitas inconsistências e ambigüidades foram encontradas no MRO. Um novo modelo, livre de todos os erros e incorporando alguns aspectos conceituais, é agora proposto e formalizado, e é chamado MR0*.MRO (Modelo de Representação de Objetos) is a Object Oriented Database Model which supports engineering application modeling. This work presents a mathematical formalization of MRO the main goals of which are: - to validate the models\'s definitions; - to depurate inconsistencies of the model; - to supply basis for comparison with other models. During the formalization process, many inconsistencies and ambiguities were found in MRO. A new model, free of those errors and incorporating conceptual enhancements, is now proposed and formalized, and is named MRO*.
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Roque, Luiz Gabriel Rossi. "Gestão de portfólio de serviços de MRO (Maintenance, Repair and Overhaul) aeronáutico: uma pesquisa ação." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/18/18156/tde-15012013-094115/.
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Os centros de manutenção de aeronaves da América Latina possuem portfólios de serviços limitados e esse é um fator que restringe o crescimento do transporte aéreo na região. Faz-se necessário, portanto, o desenvolvimento de novos serviços de reparo de aeronaves e seus componentes nesses centros. Apesar de o Desenvolvimento de Produtos ter recebido uma atenção substancial na ultima década, há pouca literatura sobre o Desenvolvimento de Serviços e trabalhos que tratam de gestão de portfólio de serviços são ainda mais escassos. A pouca literatura existente não é suficientemente abrangente para tratar da gestão de portfólio de serviços de manutenção complexa. O objetivo deste trabalho é, portanto, desenvolver um processo de gestão de portfólio de serviços para empresas de manutenção aeronáutica, chamado de modelo específico. O desenvolvimento do modelo será feito utilizando a pesquisa-ação, abordagem que objetiva tanto a tomada de ação quanto a criação de conhecimento com ciclos contínuos. Durante a criação do modelo específico foram usados como base de conhecimento modelos de referência de PDP e PDS, posteriormente adaptados para a realidade de serviços, para a região e tipologia da indústria. A pesquisa ação se iniciou numa pré-fase de contextualização, seguida por quatro ciclos, sendo que em cada ciclo uma etapa do modelo foi desenvolvida e avaliada, resultando em um modelo especifico de gestão de portfólio para indústria de MRO aeronáutico brasileiro. Ao final dos ciclos foi feita uma avaliação do processo criada por meio de um questionário. Os participantes da pesquisa avaliaram o método de desenvolvimento do modelo como adequado e avaliaram também o próprio modelo como adequado.The aircraft maintenance centers in Latin America have limited portfolios of services; this is a factor that restricts the growth of air transport in the region. Therefore is necessary to develop new maintenance, repair and overhaul (MRO) services for aircraft and their components in those centers. New Product Development (NPD) process theory has received substantial attention in the last decade but there is little literature on the New Services Development (NSD), and papers dealing directly with services portfolio management are even scarcer. The existing literature is not holistic enough to deal with maintenance services portfolio management. Therefore this paper aims to develop a services portfolio management (SPM) for aircraft components maintenance. The SPM model development will be done using the action research approach trough the creation of knowledge in continuous PDCA cycles. During the creation of the specific model, were used as knowledge base reference models of PDP and PDS, later adapted to the reality of services to the region and type of industry. The action research began in pre contextualization phase, followed by four cycles, and each cycle a stage of the model was developed and evaluated, resulting in a specific model of portfolio management for MRO Brazilian aeronautics industry. At the end of cycles an evaluation process created by means of a questionnaire. Survey participants rated the method as proper development of the model, the model itself also rated as adequate.
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Milczek, Dominica [Verfasser]. "Der MrgD-Rezeptor und seine Rolle in der Leberfibrose und deren Komplikationen im transgenen Tiermodell / Dominica Vanessa Milczek." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1218301953/34.
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Milczek, Dominica Vanessa [Verfasser]. "Der MrgD-Rezeptor und seine Rolle in der Leberfibrose und deren Komplikationen im transgenen Tiermodell / Dominica Vanessa Milczek." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1218301953/34.
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López, Gómez Carlos Enrique. "National value capture in modern industrial systems : insights for policy development." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607916.
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Toves, Peter Rocky. "Evaluating Success Factors in Implementing E-Maintenance in Maintenance, Repair, and Overhaul (MRO) Organizations." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/767.
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Despite more than a decade-long process to transition aircraft maintenance practices from paper-to electronic-based systems, some organizations remain unable to complete this transition. Researchers have indicated that while organizations have invested resources in technology improvements, there remains a limited understanding of the factors that contribute to effectively managing technology-enabled change. The purpose of this case study was to identify and explore socio-technical (ST) factors that inhibit an effective transition from a paper-based system to an electronic-based system for aircraft maintenance. A conceptual model applying theories of change management, technology acceptance, systems thinking, and ST theory informed the research. Thirteen participants provided data via semistructured interviews, field observations, follow-up interviews, other documentation, and a questionnaire. Data were analyzed with open and axial coding techniques to identify themes, which were then crosschecked and triangulated with observation and follow-up interview data. Findings revealed communication issues, a fundamental misconception in training, and a false assumption that all personnel easily acquire computer literacy. Benefits gained from this study should assist maintenance, repair, and overall (MRO) organizations within the Department of Defense to improve current and future technology implementation as the research underscores real-life issues from a comparable organization. The implications for positive social change provide a greater understanding of technology-enabled change and contribute to the development of best practices for technology initiatives that address common ST issues in the MRO workplace.
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Cardoso, André Luís. "Oportunidades e barreiras para engajamento de fornecedores brasileiros de MRO na utilização de e-procurement." reponame:Repositório Institucional do FGV, 2018. http://hdl.handle.net/10438/24862.
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Um número cada vez maior de empresas está utilizando e-procurement (EPT) em seus processos de aquisição de materiais. Essas empresas buscam aumento de competitividade através da redução dos custos administrativos, redução do preço de compras, aumento de eficiência, melhor visibilidade de gastos, entre outras vantagens. Um dos problemas encontrados para o uso de EPT se relaciona aos fornecedores, que muitas vezes possuem dificuldade em cooperar, falta de infraestrutura, imaturidade tecnológica e resistência em absorver custos extras. O objetivo desse trabalho aplicado é estudar as dificuldades e os motivadores de fornecedores de MRO (manutenção, reparo e operação) no mercado brasileiro para utilização de e-procurement nas transações negócio-a-negócio (B2B) com seus clientes. Um segundo objetivo é elaborar uma lista de recomendações para facilitar o engajamento dos fornecedores no uso dessas ferramentas. O primeiro passo para atingir esse propósito foi revisar a literatura existente a respeito do processo de compras de MRO, sobre e-procurement, incluindo dificuldades e motivadores para sua utilização. A seguir foi realizado uma pesquisa exploratória qualitativa com estudo de casos múltiplos com fornecedores de MRO que utilizam o EPT no relacionamento comercial com seus clientes. As informações coletadas a partir do estudo de caso foram analisadas e comparadas com a literatura existente, gerando quatro proposições que podem ser estudadas futuramente. Como contribuição prática, a partir das informações obtidas foi elaborada uma lista de recomendações que pode ser utilizada por profissionais de empresas compradoras, consultorias, provedores de soluções de tecnologia de informação, além dos próprios fornecedores, para reduzir as barreiras e melhorar a eficiência de uso dessas ferramentas, beneficiando toda a cadeia com ciclos mais rápidos e menores custos.
An increasing number of companies are using e-procurement (EPT) in their purchasing processes. Their goal is to increase competitiveness through the reduction of administrative costs, lower purchasing prices, increase efficiency and improve spend visibility. One of the problems found for using EPT is related to suppliers which sometimes have difficulty to cooperate, lack of infrastructure, technological immaturity and resistance for bearing extra costs. The goal of this master's thesis is to study the difficulties and motivations for MRO (maintenance, repair and operation) suppliers in the Brazilian market for adopting eprocurement in their business-to-business (B2B) transactions with their clients. A second goal is elaborate a list of recommendations to increase supplier engagement in the adoption of these tools. The first step to achieve this goal was a literature review about MRO purchasing process, e-procurement, including barriers and motivations for both buyers and suppliers. After that it was performed an exploratory qualitative research using multiple case study with MRO suppliers that use EPT in their commercial transactions with clients. The data collected from the case study was analyzed and compared with existing literature generating four propositions that can be studied in the future. As a practical contribution, based on the evidence collected it was also prepared a list of recommendations for professionals of buying companies, consultancy groups, IT solution providers, besides the suppliers, in order to mitigate barriers and improve efficiency for using those tools, benefiting the whole chain with faster cycles and lower costs.
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Caldeira, Inês Raquel Baptista. "Implementação de práticas Lean nos serviços : o caso de um processo de faturação numa MRO." Master's thesis, Instituto Superior de Economia e Gestão, 2018. http://hdl.handle.net/10400.5/19833.
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Mestrado em Gestão e Estratégia IndustrialDada a alta competitividade que caraterizam os mercados, é cada vez mais proeminente olhar as operações e processos de um ponto de vista desafiante face ao compromisso de alcançar custos mais baixos, flexibilidade e rapidez, sendo que, no âmbito empresarial decompõem-se inúmeras atividades que, apesar de serem essenciais, se apresentam como dispendiosas ou mesmo morosas à organização. Para que uma empresa alcance níveis de melhoria nas suas operações e processos, existem diferentes conceitos e abordagens. Uma das metodologias amplamente difundidas corresponde à filosofia Lean Thinking. Neste âmbito, o uso da metodologia Lean Service pode ser utilizada como forma de gerar benefícios em termos do aumento de eficiência, melhoria do desempenho operacional e aumento da satisfação do cliente. O presente estudo procede a uma análise da forma como a metodologia Lean Service foi aplicada ao processo de faturação das inspeções C-Check de aviões de clientes em manutenção, no seio de uma Maintenance Repair & Overhaul (MRO).
Given the high competitiveness of markets, it is increasingly prominent to look at operations and processes from a challenging point of view in the face of a commitment to lower costs, flexibility and speed, taking into account that in the business sphere they are broken down into countless activities that, although essential, are presented as costly or even time consuming to the organization. For a company to achieve levels of improvement in its operations and processes, there are different concepts and approaches. One of the widely disseminated methodologies is the Lean Thinking philosophy. In this context, the use of the Lean Service methodology can be used as a way of generating benefits in terms of increasing efficiency, improving operational performance and increasing customer satisfaction. The present study analyzes the way in which the Lean Service methodology was applied to the billing process of C-Check inspections of customer aircraft under maintenance, within a Maintenance Repair & Overhaul (MRO).
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Peres, Walter José. "Um modelo exploratório para o processo de compra de MRO baseadas na internet Michelin Brasil." reponame:Repositório Institucional do FGV, 2001. http://hdl.handle.net/10438/3783.
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Previous issue date: 2001The present dissertation is intended to create a purchasing model of MRO (maintenance, repair and operations) based on the Internet, for Michelin in Brazil. Current1y, Michelin' s enterprise is part of a virtual community, under the vertical portal form, created by the greatest industry enterprises in tire and rubber field (Michel in, Goodyear, Pirelli, Continental, Cooper, Sumitomo, and others), with the intention to develop a global market place to realize purchases and supplies. Rubbernetwork.com (RNC) was founded as an independent enterprise, gathering the complexities of the tire and rubber industry, which represents an amount over fifty billion dollars a year spent on raw materiais, equipment, machines, goods and services. This purchasing center will allow the members to increase the efficiency of their operations and realize great savings on business costs. Each business transaction will be protected by the appropriate systems from the implement of the information technology, with the objective to assure confidentiality for alI commercial activities on each enterprise individually. The participating members are convinced that this initiative will alIow substantial savings and it will improve their chain value. The virtual community will be opened to alI manufacturers and providers related to the tire and rubber industry, and it will also welcome interaction opportunities with other virtual communities, especially those associated to the automobile industry. 5 It is under the context of the implementation of the Rubbernetwork.com (RNC) that the dissertation will be developed, scheming strategies and concerning purchasing processes related to MRO (maintenance, repair and operations). The development of vertical portal on Internet does not impede horizontal complementary portaIs, not excluding, also to be increased as business alternative. We shall give specific attention to daily purchasing that involves a great number of different suppliers, various internaI areas in the enterprise that spend time on unnecessary bureaucratic work, without strategic finalities. We must emphasize that this category of purchasing, named MRO, despite its low value per product or acquired services, generates a huge volume oftransactions and a high operational impacto Toward the fact that is an innovated expenence In the sector with proper characteristics - tire and rubber market - , and because it is creating an expectation of cooperation between concurrent enterprises, that are searching for rationalization of purchasing process and division of operational costs, the adopted methodology, as its finality it will be exploratory and applied2 . As its investigation's means, the realized research will be: on field, study of case and bibliographic. The research' s umverse will be restricted to Michelin enterprise, where the purchasing process of MRO based on Internet will be contemplated, by the collection of facts in the USA and France, with the intent to propose a model to Michelin in Brazil.
A presente dissertação tem por objetivo criar um modelo de compras de rMRO (manutenção, reparos e operações) baseado na Internet, para a Michelin no Brasil. Atualmente, a empresa Michelin está participando de uma comunidade virtual, sob a forma de um 'vertal', criada pelas maiores empresas da indústria de pneu e borracha (Michelin, Goodyear, Pirelli, Continental, Cooper, Sumitomo, entre outras), e cuja intenção é desenvolver uma praça de mercado global para realização das suas compras e aprovisionamentos. A Rubbernetwork.com (RNC) foi fundada como uma empresa independente, reunindo o conjunto das compras da indústria de pneu e borracha, representando um valor de mais de cinqüenta bilhões de dólares por ano gastos em matérias-primas, equipamentos, maquinário, bens e serviços. Esta central de compras permitirá a seus membros aumentar a eficácia de suas operações e realizar economias substanciais nos custos de transação. Cada transação será protegida por apropriados sistemas advindos da implementação da tecnologia da informação, a fim de garantir a confidencialidade de todas as atividades comerciais de cada empresa individualmente. Os membros participantes estão convencidos de que a iniciativa possibilitará economias significativas e melhorará a eficiência de suas cadeias de valor. A comunidade virtual será aberta a todos os fabricantes e fornecedores relacionados à indústria de pneu e borracha, sendo também bem vindas oportunidades 2 de interação com outras comunidades virtuais, especialmente aquelas associadas à indústria automotiva. É dentro do contexto de implementação do projeto Rubbernetwork.com (RNC) que a dissertação se desenvolverá, tecendo estratégias e modelos de negócios concernentes aos processos de compras relacionados a MRO (manutenção, reparos e operações). O desenvolvimento de um 'vertal' na Internet não impede que portais horizontais complementares, e não excludentes, sejam também acrescidos como alternativa de negócios. Há de se dar um tratamento específico às compras diárias que envolvem um grande número de diferentes fornecedores, várias áreas internas na empresa e consomem tempo desnecessário em trabalhos burocráticos, sem fins estratégicos. Cabe ressaltar que tal categoria de compras, denominada MRO, apesar de seu baixo valor por produto ou serviço adquirido, gera um elevado volume de transações e um alto impacto operacional. Pelo fato de tratar-se de uma experiência inovadora em setor de características próprias - mercado de pneu e borracha -, e de estar-se criando uma expectativa de cooperação entre empresas concorrentes, em busca da racionalização do processo de compras e divisão de custos operacionais, a metodologia utilizada, quanto aos seus fins, será exploratória e aplicada I. Quanto aos meios de investigação, a pesquisa realizada será: de campo, estudo de caso e bibliográfica. O universo da pesquisa restringir-se-á à empresa Michelin, onde o processo de compras de MRO baseado na Internet será contemplado, através de levantamento de dados nos E.UA e França, a fim de propor-se um modelo para a Michelin Brasil.
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Li, Xingru. "Wilms' tumor gene 1 in different types of cancer." Doctoral thesis, Umeå universitet, Institutionen för medicinsk biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-103389.
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The Wilms’ tumor gene 1 (WT1) was first reported as a tumor suppressor gene in Wilms’ tumor. However, later studies have shown the oncogenic properties of WT1 in a variety of tumors. It was recently proposed that WT1 was a chameleon gene, due to its dual functions in tumorigenesis. We aimed to investigate the clinical significance of WT1 as biomarker in acute myeloid leukemia (AML) and clear cell renal cell carcinoma (ccRCC) and to elucidate the function of WT1 as an oncogene in squamous cell carcinoma of head and neck (SCCHN). In AML, it was suggested that WT1 expression was an applicable marker of minimal residual disease (MRD). In adult patients with AML, we found a good correlation between WT1 expression levels normalized to two control genes, β-actin and ABL. Outcome could be predicted by a reduction in WT1 expression in bone marrow (≥ 1-log) detected less than 1 month after diagnosis, when β-actin was used as control. Also, irrespective of the control gene used, outcome could be predicted by a reduction in WT1 expression in peripheral blood (≥ 2-log) detected between 1 and 6 months after treatment initiation. Previous studies in RCC demonstrated that WT1 acted as a tumor suppressor. Thus, we tested whether single nucleotide polymorphisms (SNPs) or mutations in WT1 might be associated with WT1 expression and clinical outcome in patients with ccRCC. We performed sequencing analysis on 10 exons of the WT1 gene in a total of 182 patient samples, and we identified six different SNPs in the WT1 gene. We found that at least one or two copies of the minor allele were present in 61% of ccRCC tumor samples. However, no correlation was observed between WT1 SNP genotypes and RNA expression levels. Moreover, none of the previously reported WT1 mutations were found in ccRCC. Nevertheless, we found that a favorable outcome was associated the homozygous minor allele for WT1 SNP. We then further investigated whether WT1 methylation was related to WT1 expression and its clinical significance. Methylation array and pyrosequencing analyses showed that the WT1 promoter region CpG site, cg22975913, was the most frequently hypermethylated CpG site. We found a trend that showed nearly significant correlation between WT1 mRNA levels and hypermethylation in the 5’-untranslated region. Hypermethylation in the WT1 CpG site, cg22975913, was found to be associated with patient age and a worse prognosis. One previous study reported that WT1 was overexpressed in SCCHN. That finding suggested that WT1 might play a role in oncogenesis. We found that both WT1 and p63 could promote cell proliferation. A positive correlation between WT1 and p63 expression was observed, and we identified p63 as a WT1 target gene. Furthermore, several known WT1 and p63 target genes were affected by knocking down WT1. Also, co-immunoprecipitation analyses demonstrated a protein interaction between WT1 and p53. In summary, WT1 gene expression can provide useful information for MRD detection during treatment of patients with AML. In RCC, our results suggested that the prognostic impact of WT1 SNPs was limited to the subgroup of patients that were homozygous for the minor allele, and that WT1 promoter hypermethylation could be used as a prognostic biomarker. In SCCHN, WT1 and p63 acted as oncogenes by affecting multiple genes involved in cancer cell growth.
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ISLAM, MAHMUDUL, and TAN ZHU. "DRIVING FORCES AND HINDERING FACTORS OF E-PROCUREMENT ADOPTION FOR MRO PRODUCTS IN BANGLADESH AND CHINA." Thesis, Linnéuniversitetet, Ekonomihögskolan, ELNU, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-21241.
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Summary: Business Administration, Business Process & Supply Chain Management, Degree Project (master), 30 higher education credits, 5FE02E, Spring 2012 Authors: Mahmudul Islam and Tan Zhu Tutor: Peter Berling Date: May, 2012 Keywords: e-procurement, MRO procurement, e-procurement implementation, driving forces of e-procurement, hindering factors of e-procurement Title: Driving forces and hindering factors of e-procurement adoption for MRO products in Bangladesh and China. Background: MRO (Maintenance, Repair and Operations procurement) materials, as time goes by, are now attracting more and more enterprises´ attentions due to their enormous varieties, large quantity and huge cost. The traditional MRO procurement method has the problem of lacking of centralized management, funds, and channels, short of products and information flow. Meanwhile, e-procurement (electronic procurement), due to its advance, has nowadays been introduced to more and more enterprises for procuring mainly MRO materials, which leads to much savings and efficiency. Purpose: The purpose of this thesis is aiming at throwing light upon two cases: one is BATA shoes in Bangladesh and one is GE aviation group in China, the driving forces and hindrances of their electronic procurement for MRO goods. Thereafter the authors intend to compare both cases according to the empirical findings and draw some future suggestions. Method: In this thesis, the authors will employ qualitative multiple case studies method in the combination of interview and questionnaires with both cases to create the deep understanding of e-procurement implementation of them. Results, conclusion: First, the current status of e-procurement implementation for MRO materials will be explained in the within-case analysis. Then, the internal driving forces and hindrances of each case will be thoroughly analysed according to the four sections-perceived benefits, perceived critical success factors, future organizational performance and perceived barriers in the theoretical framework. Finally, the authors will use cross-case analysis comparing both cases´ driving forces and hindrances according to the model, in order to draw systematic future suggestions for BATA shoes in Bangladesh with GE´s successful views. Future work: The authors find it interesting that in the future if the seller firms´ perspective on e-procurement implementation for MRO materials could be studied. Also a quantitative study on e-procurement for MRO, its impact on organizational performance would be very interesting subject to focus on. Moreover, a study in the background of different countries, their cultural influences on e-procurement implementation would also be a suggestion.
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Gille, Christine [Verfasser], and Karsten [Akademischer Betreuer] Spiekermann. "MRD-Monitoring bei AML-Patienten mittels Hochdurchsatz-Amplikonsequenzierung (NPM1 Mutation A) / Christine Gille ; Betreuer: Karsten Spiekermann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1229835466/34.
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Jensen, Kai-Ole [Verfasser]. "Monitoring minimaler Resterkrankung (MRD) bei der akuten myeloischen Leukämie (AML) mit NPM1 Mutation / Kai-Ole Jensen." Ulm : Universität Ulm, 2016. http://d-nb.info/1110969465/34.
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Ayeni, P. "Enhancing competitive advantage through successful lean realisation within the aviation Maintenance Repair and Overhaul (MRO) industry." Thesis, Cranfield University, 2015. http://dspace.lib.cranfield.ac.uk/handle/1826/11317.
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Purpose: Lean is increasingly being applied within the aviation Maintenance and Repair (MRO) Industry to mitigate industry challenges. This Lean application is premised on its success within other industrial contexts particularly the automotive industry. Furthermore, many organisations within automotive industry have attributed their enhanced competitive positioning to the Lean application. Indeed, Toyota (a pioneer of Lean) present Lean as a key proponent to its global success. However, with literature suggesting that there cannot be a direct transference of Lean from one industry to another and with the MRO having distinct characteristics different from the automotive industry, this research seeks to present how competitive advantage can be achieved through successful Lean realisation. Design/Methodology/Approach: The status of MRO Lean engagements presented is first presented based on the syntheses of literature review and empirical study (facilitate by an industry-wide survey). The means through which the MRO realises its value proposition is established and the structural assessment of the MRO industry as it pertains to competitiveness is also defined. The role of Lean in enhancing the value delivery system to enhance competitive positioning is operationalised through a case study. Findings: Using Porter’s forces of competition, this research establishes the competitive MRO landscape revealing the distinct characteristics of the MRO industry and how Lean can be accurately appropriated to enhance competitive advantage. The MRO Value Delivery System (VDS) is also delineated providing the complete system within which Lean is to be deployed (as opposed to the prevalent limited application of Lean in operational context alone). The case exemplar successfully validates and operationalises the approach to Lean application within MRO to enhance competitive advantage. Research Limitations: A case study example was used for this research, and whilst the outcomes were consistent with the research proposal, it still requires wider validation. Practical and Social Implications: This research demystifies and helps MRO organisations in assessing their Lean engagements but also in provide a roadmap and informs their strategy in improving their competitive status through Lean realisation.
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Antrobus, Jared E. "The State of Lexicodes and Ferrers Diagram Rank-Metric Codes." UKnowledge, 2019. https://uknowledge.uky.edu/math_etds/66.
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In coding theory we wish to find as many codewords as possible, while simultaneously maintaining high distance between codewords to ease the detection and correction of errors. For linear codes, this translates to finding high-dimensional subspaces of a given metric space, where the induced distance between vectors stays above a specified minimum. In this work I describe the recent advances of this problem in the contexts of lexicodes and Ferrers diagram rank-metric codes.
In the first chapter, we study lexicodes. For a ring R, we describe a lexicographic ordering of the left R-module Rn. With this ordering we set up a greedy algorithm which sequentially selects vectors for which all linear combinations satisfy a given property. The resulting output is called a lexicode. This process was discussed earlier in the literature for fields and chain rings. We describe a generalization of the algorithm to finite principal ideal rings.
In the second chapter, we investigate Ferrers diagram rank-metric codes, which play a role in the construction of subspace codes. A well-known upper bound for dimension of these codes is conjectured to be sharp. We describe several solved cases of the conjecture, and further contribute new ones. In addition, probabilities for maximal Ferrers diagram codes and MRD codes are investigated in a new light. It is shown that for growing field size, the limiting probability depends highly on the Ferrers diagram.
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Peterson, Reginald E. "Exploring Customers' Perceptions of Third Party Maintenance, Repair, and Operating Programs." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2170.
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A survey of 25 industrial manufacturing organizations in the U. S. indicated that 70% of respondents experienced dissatisfaction with their outsourcing programs due to unfulfilled expectations, which caused negative continuance intentions. The purpose of this descriptive case study was to explore the experiences of customers who currently use 3PMRO outsourcing programs to determine what factors affect satisfaction levels in the Southern United States. The conceptual framework for this study was the expectancy disconfirmation paradigm, which connects consumer satisfaction level to the fulfillment of consumer expectations. Data were collected from interviews of 22 procurement professionals of maintenance, repair, and operating supplies; observations of 3PMRO supplier performance meetings; and the analysis of performance scorecard documents. Data were analyzed using pattern matching followed by thematic analysis. Three themes were identified through the data analysis that affected consumer satisfaction: inventory management services, utilization of outsourced labor resources, and total cost value of the 3PMRO program. According to results, satisfaction of 3PMRO consumers are based on the proper utilization of a 3PMRO program for the intended limitations of the organization, reduced MRO supply costs, improved inventory management strategies, and improved competitive advantage from the realignment of resources to focus on core competencies. Implications for positive social change include increased awareness of cradle-to-grave inventory management to prevent improper disposal of non-biodegradable materials into our environment.
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Grima, Cyril. "Etude de la surface et de la subsurface de Mars par sondage radar. Analyse des données MRO/Sharad." Phd thesis, UNIVERSITE DE GRENOBLE, 2011. http://tel.archives-ouvertes.fr/tel-00583703.
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Le radar sondeur Sharad (NASA/ASI) prospecte actuellement la surface et le sous-sol de Mars àune fréquence de 20 ±5 MHz depuis une orbite polaire basse (Mars Reconnaissance Orbiter).L'instrument a pour but de contraindre la composition du sol et de détecter, puis d'interpréter, desinterfaces enfouies afin de restituer le contexte géologique martien à l'échelle régionale. Ce travail dethèse se propose de contribuer à ces objectifs en se focalisant principalement sur l'étude de terrainsglaciaires et péri-glaciaires Martien.Dans un premier temps, par une méthode d'inversion impliquant la reconstruction d'un sousbassementrocheux par interpolation, nous obtenons les paramètres diélectriques représentatifs duvolume de glace d'eau constituant la calotte polaire Nord, Planum Boreum. Nous en déduisons un tauxde pureté du matériel glaciaire > 95 %. Nous fournissons une carte de l'épaisseur des dépôts qui vérifieun volume de glace de 1,14106 km3.Dans une deuxième étude, en confrontant les transects Sharad à des données topographiques etd'imagerie visible, nous élaborons un profil morphologique et stratigraphique complet d'escarpementsglaciaires présents dans la région d'Ultimi Lobe, Planum Australe. Nous appelons ces escarpements"Laps" (large and assymetric polar scarps). La similarité avec des failles listriques associées à desanticlinaux de roll-over nous amène à proposer l'hypothèse de macro-ruptures mécaniques d'une glacesous contrainte extensive et d'un mouvement subséquent par glissement basal.Puis, nous nous intéressons à la réflectivité radar de la surface dont l'amplitude dépend de larugosité et de la permittivité du sol. Nous élaborons une méthode nous permettant de construire unecarte globale de la réflectivité. Afin de séparer les paramètres physiques qui constituent ce signal, nousproposons des méthodes statistiques simples, inspirés du SAR (radar à synthèse d'ouverture) terrestre,complétées par l'élaboration de modèles de rétrodiffusion de surface à incidence normale. Nousmontrons des résultats de cette approche et leur adéquation avec les modèles théoriques. Enfin, nousmettons en évidence une variation temporelle de la réflectivité aux pôles que nous attribuons à laprésence des condensats saisonniers de CO2. Notre méthode d'analyse statistique de la réflectivité,associée à un modèle de rétrodiffusion à trois couches, nous permet d'évaluer la variation d'épaisseurdes condensats dans des régions à très hautes latitudes (80°-85°).
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Carter, John. "Étude des minéraux hydratés à la surface de Mars par les imageurs hyperspectraux OMEGA/MEx et CRISM/MRO." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00657804.
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La planète Mars a connu une période où l'eau liquide était durablement stable. Outre les vestiges morphologiques d'une activité hydrologique en surface, l'interaction chimique de l'eau avec la croûte basaltique s'est traduite par la formation d'argiles et de sels hydratés en surface et en profondeur. Ces minéraux hydratés ont été détectés à la surface de Mars en 2004 grâce à l'instrument OMEGA, l'imageur hyperspectral infrarouge proche embarqué sur la sonde européenne Mars Express. Leur étude permet de reconstruire l'histoire de l'activité aqueuse sur Mars et de caractériser une période ancienne où l'environnement a pu être favorable à l'apparition d'une chimie pré-biotique. Ce travail de thèse s'intéresse aux environnements aqueux de Mars en couplant les données minéralogiques des imageurs hyperspectraux embarqués OMEGA/Mars Express et CRISM/Mars Reconnaissance Orbiter avec la morphologie. De nouveaux outils de traitement et d'analyse des données sont développés et ont permis la détection et la caractérisation spectrale de plus d'un millier de dépôts de minéraux hydratés sur Mars, fournissant une vue d'ensemble de l'altération. Celle-ci a eu lieu principalement dans la première partie du Noachien et a surtout formé des phyllosilicates ferro-magnésiens de la famille des vermiculites et smectites. Une importante diversité minérale est par ailleurs constatée avec une dizaine de familles minérales différentes, traçants des conditions géo-chimiques variées. Placés dans leur contexte géologique, certaines détections permettent de proposer l'existence passée d'un système hydrologique sur l'ensemble de la planète qui a donné naissance à un cycle des argiles similaire au cycle terrestre. Il apparait par ailleurs que les cratères d'impact sont le contexte privilégié des minéraux hydratés, mais le lien entre ces derniers et les processus d'impact demeure ambigu. La découverte d'un cycle des argiles est compatible avec l'hypothèse d'une planète potentiellement habitable au Noachien mais qui devra être vérifiée par l'exploration in-situ.
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Cámero, Taboada Carlos Manuel. "Análisis y mejora del proceso de Suministros de MRO, Servicios y CAPEX en la Empresa Siderúrgica del Perú." Master's thesis, Universidad Peruana de Ciencias Aplicadas - UPC, 2015. http://hdl.handle.net/10757/338568.
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La política de abastecimiento en una empresa es una necesidad estratégica, ya que Suministros es uno de los eslabones de la cadena de abastecimiento donde se pueden establecer diferencias con otras empresas agregando valor a la operación, aportando en estos programas de mejoras de costos y a la rentabilidad de la compañía. El presente trabajo se propone planes de acción y soluciones para mejorar lo que el cliente interno percibe como la calidad del servicio que Suministros le debe ofrecer y como tal se identifican a la puntualidad y un bajo nivel de servicio como factores a mejorar, para que las plantas productivas operen con mayor eficiencia. Se describe y analiza el proceso actual de Suministros de MRO (Maintenance, repair and operations), Servicios y Capex, que se inicia con una descripción actual de la empresa, incluyendo sus procesos productivos donde trabajan los principales clientes internos, para luego pasar al análisis de Suministros y la identificación de las principales variables que se deben mejorar utilizando herramientas como la Casa de la Calidad y el Diagrama de Ishikawa. Luego, se plantean las soluciones y las mejoras al nivel de servicio de Suministros. Se puede observar que, aplicando las herramientas de calidad, se identifican las variables que afectan al proceso de Suministros y luego filosofías como la del lean y el JIT se aplican al proceso reduciendo actividades que no agregan valor y mejoran la eficacia y gestión de Suministros. Asimismo, se establecen planes de acción atacando las causas raíces de los problemas, alineado a la mejora de la puntualidad y nivel de servicio.
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Kazim, R. Y. "A system dynamics approach for assessing supply chain management integrated policies and strategies in an aircraft MRO company." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/7117/.
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Seeger, Karlheinz. "Rezidive von akuten lymphoblastischen Leukämien im Kindesalter." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2003. http://dx.doi.org/10.18452/13899.
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Die akute lymphoblastische Leukämie (ALL) ist die häufigste maligne Erkrankung im Kindesalter. Trotz risikoadaptierter Chemotherapie erleiden 25 - 30 % der Kinder mit ALL ein Rezidiv. Im Rezidivfall liegen die Heilungschancen trotz intensivierter Therapie nur bei 35- 40%. In retrospektiven und prospektiven Analysen konnten wir einerseits prognostisch-relevante, genetische Merkmale in den Leukämiezellen von Kindern mit ALL-Rezidiv erstmals identifizieren. Diese leukämiespezifischen Merkmale umfassen sowohl Translokations-assoziierte Fusionsgene (TEL-AML1, BCR-ABL, MLL-Aberrationen, E2A-PBX1), Deletionen von Tumorsuppressorgenen (p15, p16, p18) als auch Mutationen in DNA-Reparaturgenen (NBS1). Zusammen mit der sensitiven molekularen Bestimmung der Kinetik der Leukämiezellreduktion (Reaktion auf die Therapie, (MRD, minimal residual disease)) läßt sich die Prognose der Kinder mit ALL-Rezidiv durch die Verwendung dieser Marker zuverlässiger bewerten. Andererseits zeigen unsere Analysen, dass das Ansprechen auf die Therapie und die Prognose von wirtseigenen Faktoren (medikamenten metabolisierenden Enzyme) und von der Interaktion zwischen Leukämie- und Stromazellen und löslichen Wachstumsfaktoren (Zytokinen) abhängt. Eine adäquatere Behandlung dieser Patientengruppe, die bereits eine intensive Therapie erhalten hat und wesentlich risikoreichere, mit einer hohen Akut- und Spättoxizität behaftete Therapieverfahren einschließt, lässt sich durch die Berücksichtigung dieser Ergebnisse erreichen. Die genetische Typisierung und die sensitive Quantifizierung des molekularen Ansprechens auf die Therapie ergänzen heute die klinischen Determinanten zur Risikostratifizierung der Kinder mit ALL-Rezidiv der derzeitigen Therapieoptimierungsstudie ALL-REZ BFM 2002 (Berlin-Frankfurt-Münster).Acute lymphoblastic leukemia is the most common malignancy in childhood. Although the prognosis for pediatric ALL with risk-adapted chemotherapy has improved dramatically, 25-30% of the children suffer a relapse. The prognosis for relapsed ALL remains poor (35-40%). In retrospective and prospective studies, we identified prognostic-relevant genetic features in leukemic blasts from children with ALL relapse. These leukemia-specific aberrations include translocation-associated fusion genes (TEL-AML1, BCR-ABL, MLL changes, E2A-PBX1), deletions of tumor suppressor genes (p15, p16, p18) and point mutations in DNA repair genes (NBS1). Together with the sensitive quantitative assessment of the molecular response to therapy (MRD, minimal residual disease), prediction of outcome is now more reliable. Furthermore, response to therapy and, thus, prognosis is significantly dependent on modifying host factors (drug-metabolizing enzymes) and interactions between leukemic and stromal cells as well as soluble growth factors (cytokines). Today, the genetic characterization of leukemic cells as well as the molecular quantification of response to therapy complement prognostic significant clinical determinants allowing a more precise risk stratification of children with ALL relapse in the relapse trial ALL-REZ BFM 2002 of the BFM (Berlin-Frankfurt-Münster) study group.
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MELO, Rita de Cássia Andrade. "Isolados clínicos de Klebsiella pneumoniae produtores e não produtores de KPC: relação com a presença dos genes de virulência fimH, mrkD e irp2." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/11662.
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Klebsiella pneumoniae é um patógeno oportunista frequentemente associado a infecções hospitalares do trato respiratório e do trato urinário de indivíduos imunocomprometidos e neonatos, e podem produzir diferentes tipos de fatores de virulência, como adesinas fimbriais (genes fimH e mrkD ) e sideróforos, como a yersiniabactina (gene irp2), importantes no desenvolvimento da infecção. O objetivo do presente estudo foi determinar a ocorrência dos genes de virulência fimH, mrkD e irp2 em isolados de K. pneumoniae produtores e não produtores de KPC, provenientes de pacientes de diferentes hospitais de Recife-PE, como também a relação clonal, através da ERIC-PCR, e o perfil de susceptibilidade a antimicrobianos desses isolados bacterianos. Para esse estudo foram selecionados 23 isolados produtores de KPC e 23 isolados não produtores de KPC, todos da espécie K. pneumoniae. Os genes de virulência foram detectados através da PCR e sequenciamento de DNA. Analisando o perfil de susceptibilidade aos antimicrobianos dos isolados selecionados, observamos que a amicacina (n=39/ 84,78%) e a polimixina (n=41/ 89,13%), foram os antimicrobianos de melhor atividade para inibir a K. pneumoniae, tanto KPC-positivas quanto negativas, onde observamos que 5 isolados apresentaram resistência a polimixina, sendo 3 no grupo KPC-positivo e 2 no grupo KPC-negativo. Esse é o primeiro relato da resistência de K. pneumoniae à polimixina. No grupo KPC-positivo foi observada uma alta taxa de resistência à cefalosporinas, seguidas dos carbapenêmicos. Ficou evidenciado que o ertapenem é o melhor antimicrobiano para detectar resistência fenotípica ao grupo dos carbapenêmicos. A tipagem pela ERIC-PCR gerou 37 perfis genéticos, demonstrando que houve Uma disseminação multiclonal de isolados de K. pneumoniae em Recife-PE, Brasil. Dentre os 46 isolados analisados pela ERIC-PCR, cincoperfis agruparam mais de um isolado bacteriano com relação clonal. No presente estudo não foi possível detectar a relação direta entre a presença do gene blaKPC com cada gene de virulência individualmente, visto que os grupos estudados, KPC-positivo e KPC-negativo, apresentaram presenças semelhantes dos genes de virulência. Por outro lado, foi observado que os genes de virulência irp2, mrkD e fimH apresentaram-se juntos com uma maior frequência no grupo KPC-positivo. O acúmulo de genes de virulência em isolados de K. pneumoniae KPC positivos, observado nesse estudo, juntamente com a multirresistência, impõe relevantes limitações terapêuticas no tratamento de infecções causadas por K. pneumoniae em Recife-PE, Brasil.
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Woodward, Eleanor. "The use of gene expression profiling to identify novel minimal residual disease markers (MRD) in acute myeloid leukaemia (AML)." Thesis, Cardiff University, 2010. http://orca.cf.ac.uk/55179/.
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Acute myeloid leukaemia (AML) is a heterogeneous disorder characterised by the accumulation of immature haematopoietic cells blocked at various stages of differentiation. Despite improved survival rates over the past decade, relapse occurs in approximately 70% patients undergoing chemotherapy. A potential reason for this is that current clinical protocols do not take account of the level of residual disease present at remission. Therefore, one strategy to reduce relapse rates is to monitor minimal residual disease and continue to treat until the patient is minimal residual disease negative. Current minimal residual disease markers are available for patients with characterised fusion genes but approximately 50% of patients have no detectable chromosomal aberration and therefore are without markers. Gene expression profiling is a powerful tool for disease classification, prognosis and therapeutic predictions. This study aimed to investigate the use gene expression profiling to identify novel minimal residual disease markers for specific AML sub-groups. Patient diagnostic samples were profiled to identify genes specific to AML patients with a favourable translocation in order to establish the "proof-of-principle". Several genes identified were followed in patient diagnostic and follow- up samples and compared to the markers currently used. Continuing with normal karyotype AML, genes were identified as specific to this sub-group. Several homeobox (HOX) genes and the Wilms' tumour (WT1) gene were identified and their MRD levels followed in diagnostic and follow-up samples. Only WT1 identified as specific to normal karyotype AML met the necessary criteria to be an MRD marker. Although the majority of genes selected from the GEP in this study proved unsuitable as markers, the identification and validation of a marker already used for MRD monitoring, WT1, demonstrates the ability of gene expression profiling to identify potential minimal residual disease markers in normal karyotype AML.
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Yarkin, Yasemin. "Vergleichende Sequenzanalyse von Immunglobulin- und T-Zell-Rezeptor-Rearrangements vor und nach Stammzelltransplantation zur Charakterisierung der Minimalen Resterkrankung (MRD)." [S.l. : s.n.], 2009.
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