893 resultados para enterprise architecture management, architecture principles, exploratory research, expert study
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Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing unique opportunities. This thesis describes an emerging microfluidics-based toolkit for single cell functional proteomics, focusing on the development of the single cell barcode chips (SCBCs) with applications in fundamental and translational cancer research.
The microchip designed to simultaneously quantify a panel of secreted, cytoplasmic and membrane proteins from single cells will be discussed at the beginning, which is the prototype for subsequent proteomic microchips with more sophisticated design in preclinical cancer research or clinical applications. The SCBCs are a highly versatile and information rich tool for single-cell functional proteomics. They are based upon isolating individual cells, or defined number of cells, within microchambers, each of which is equipped with a large antibody microarray (the barcode), with between a few hundred to ten thousand microchambers included within a single microchip. Functional proteomics assays at single-cell resolution yield unique pieces of information that significantly shape the way of thinking on cancer research. An in-depth discussion about analysis and interpretation of the unique information such as functional protein fluctuations and protein-protein correlative interactions will follow.
The SCBC is a powerful tool to resolve the functional heterogeneity of cancer cells. It has the capacity to extract a comprehensive picture of the signal transduction network from single tumor cells and thus provides insight into the effect of targeted therapies on protein signaling networks. We will demonstrate this point through applying the SCBCs to investigate three isogenic cell lines of glioblastoma multiforme (GBM).
The cancer cell population is highly heterogeneous with high-amplitude fluctuation at the single cell level, which in turn grants the robustness of the entire population. The concept that a stable population existing in the presence of random fluctuations is reminiscent of many physical systems that are successfully understood using statistical physics. Thus, tools derived from that field can probably be applied to using fluctuations to determine the nature of signaling networks. In the second part of the thesis, we will focus on such a case to use thermodynamics-motivated principles to understand cancer cell hypoxia, where single cell proteomics assays coupled with a quantitative version of Le Chatelier's principle derived from statistical mechanics yield detailed and surprising predictions, which were found to be correct in both cell line and primary tumor model.
The third part of the thesis demonstrates the application of this technology in the preclinical cancer research to study the GBM cancer cell resistance to molecular targeted therapy. Physical approaches to anticipate therapy resistance and to identify effective therapy combinations will be discussed in detail. Our approach is based upon elucidating the signaling coordination within the phosphoprotein signaling pathways that are hyperactivated in human GBMs, and interrogating how that coordination responds to the perturbation of targeted inhibitor. Strongly coupled protein-protein interactions constitute most signaling cascades. A physical analogy of such a system is the strongly coupled atom-atom interactions in a crystal lattice. Similar to decomposing the atomic interactions into a series of independent normal vibrational modes, a simplified picture of signaling network coordination can also be achieved by diagonalizing protein-protein correlation or covariance matrices to decompose the pairwise correlative interactions into a set of distinct linear combinations of signaling proteins (i.e. independent signaling modes). By doing so, two independent signaling modes – one associated with mTOR signaling and a second associated with ERK/Src signaling have been resolved, which in turn allow us to anticipate resistance, and to design combination therapies that are effective, as well as identify those therapies and therapy combinations that will be ineffective. We validated our predictions in mouse tumor models and all predictions were borne out.
In the last part, some preliminary results about the clinical translation of single-cell proteomics chips will be presented. The successful demonstration of our work on human-derived xenografts provides the rationale to extend our current work into the clinic. It will enable us to interrogate GBM tumor samples in a way that could potentially yield a straightforward, rapid interpretation so that we can give therapeutic guidance to the attending physicians within a clinical relevant time scale. The technical challenges of the clinical translation will be presented and our solutions to address the challenges will be discussed as well. A clinical case study will then follow, where some preliminary data collected from a pediatric GBM patient bearing an EGFR amplified tumor will be presented to demonstrate the general protocol and the workflow of the proposed clinical studies.
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Part 8: Business Strategies Alignment
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The purpose of this research is to study the portable or reassemblable architectures, which, different from conventional architecture (whose designs are of permanent buildings), corresponds to the designing of spaces with temporary purposes. The focus of the study is the architectural design of spaces that are produced from building systems that can to be moved to different places (process of assembly / disassembly / reassembly) in order to identify the types of spaces generated and the processes used in their design / projecting. The aim is to investigate relationships between the initial project conceived based on a Reassemblable Construction System (RCS) and its application in the architectural design of professionals and students in order to contribute to the understanding of the specificities of this type of design activity. To this end it was developed the exploratory research based on multimedia methods, which includes: documentary analysis, technical visits, interviews, surveys, academic exercise and documentation by images. Although the study is not conclusive, the results indicate significant differences between the point of view of the RCS´s designers and its users (architects and architecture students) since the users demonstrated to have some difficulty to access the features provided for the first group, in particular the students. It is also demonstrated that the use of RCSs seems to change the appreciation / hierarchization of the conditions of project design, since, unlike what happens in traditional architectural design, the designers who use them seem to be more concerned with constructive issues, especially the structural elements (support and covering), instead of functionality, aesthetics and even physical characteristics of the site
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Tese (doutorado)—Universidade de Brasília, Centro de Desenvolvimento Sustentável, 2013.
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A ISO 9001 e Arquiteturas Empresariais (AE), diferentes ferramentas de Governação com diferentes perspetivas, são dominantes entre os seus praticantes. Uma representação de uma ISO 9001 em ArchiMate pode potenciar ainda mais alinhamentos com outras frameworks representadas por AE e pode ajudar na obtenção de melhores resultados na implementação da Qualidade numa organização, obviando os custos e a duplicação de esforços. Esta tese propõe uma abordagem de integração entre a ISO 9001 e AE na perspetiva das AE ao propor um mapeamento de conceitos de ISO 9001 em EA pela definição de uma Arquitetura de Referência da ISO 9001 utilizando a linguagem de modelação do ArchiMate Dois objetivos são endereçados: a demonstração da capacidade de representar todos os requisitos da ISO 9001 em componentes de AE através do desenvolvimento da Arquitetura de Referência e reciprocamente a capacidade de desenvolver uma AE de um Sistema de Gestão da Qualidade (SGQ) teórico baseado na ISO 9001 com as componentes dessa Arquitetura de Referência. Adicionalmente, ao identificar e avaliar a existência das componentes da Arquitetura de Referência numa organização concreta, se estes não estão completamente mapeados, pode-se concluir a existência de um desvio relativamente ao referencial ISO 9001. Por ultimo, uma Arquitetura de Referência ArchiMate da ISO 9001 permite a partilha de conhecimento, a comunicação entre partes interessadas e contribui para a discussão e validação da ISO 9001 entre os utilizadores de Arquiteturas Empresariais.
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The purpose of this study is to analyze the existing literature on hospitality management from all the research papers published in The International Journal of Hospitality Management (IJHM) between 2008 and 2014. The authors apply bibliometric methods – in particular, author citation and co-citation analyses (ACA) – to identify the main research lines within this scientific field; in other words, its ‘intellectual structure’. Social network analysis (SNA) is also used to perform a visualization of this structure. The results of the analysis allow us to define the different research lines or fronts which shape the intellectual structure of research on hospitality management.
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This study analyzes the manifestation of the dimensions of Entrepreneurial Orientation (EO) and Project Management Systems (PMS). We used a qualitative approach to conduct exploratory research through a study in literature and a pilot case in a software company. Data was collected from semi structured interviews, documents, and records on file, then triangulated and treated with content analysis. The model proposed for the relationship between the types of PMS (ad hoc, Classic PM, innovation, entrepreneurship/intrapreneurship) and the dimensions of EO (innovativeness, risk-taking, proactiveness, competitive aggressiveness, and autonomy), was partially corroborated by empirical studies. New studies are suggested to validate the applicability and setup of the model.
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El estudio del potencial exportador colombiano de carne bovina y porcina a la Federación Rusa en función de su oferta y demanda es un proyecto que pertenece a la línea de realidad dentro del área de investigación de la Universidad del Rosario. Es una investigación tipo exploratoria con un enfoque cualitativo que buscará dar respuesta a si Colombia cuenta con el potencial exportador de carne bovina y porcina al mercado de la Federación Rusa. El marco teórico que justifica el proyecto de investigación se compone de la investigación de mercados, el estudio del potencial de la demanda y las restricciones de acceso a otros mercados. A su vez los resultados esperados del proyecto de investigación serán diagnosticar el potencial exportador que tiene Colombia en relación a la carne bovina y porcina, así como examinar la oferta y demanda de estos productos en el mercado de la Federación Rusa y por último detallar las medidas sanitarias y zoosanitarias exigidas por el mercado de la Federación Rusa. Finalmente se utilizarán herramientas de tipo cualitativo que soportarán el desarrollo del proyecto de investigación, para conseguir alinear el objetivo del proyecto con el de la línea de realidad de la universidad y al objetivo del profesor, que buscan la producción de materiales académicos de uso permanente en la Universidad.
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This paper provides a complete description of the Commercial Education Professional Competency Profile that resulted from the curricular diagnosis of the Licenciatura en Educación Comercial , at the Universidad Nacional, Costa Rica. The methodological strategy used relies on the principles of research on education. Upon expert validation, written questionnaires were applied to first-year students, students of the licenciatura, practicing professionals and employers. The objective was to describe a particular education situation. Data was analyzed according to two categories: intentions/principles and scope/development. The findings resulted in the characteristics of the Commercial Education professionals, i.e. characteristics related to the discipline, characteristics related to the administrative management of teaching, specific and general characteristics of education and pedagogy, and characteristics associated to human development. Based on those criteria, on the curricular requirements of the information sources and on the curricular perspectives of the Academic Unit, ideas were put into practice to build the competency profile. The ideas proposed comprise the curricular fundamentals of the educational project on which the profile is set out, which include the subject of the study program, the global competency or training goal, the generic competencies as cross-cutting approaches, as well as the –pedagogical and disciplinary− specific competencies. The specific competencies of the discipline are focused on four competency areas: document production, organizational support, technological resources and information management.(1) Translator’s Note: One-year post-Bachelor study program in Commercial Education.
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OBJETIVO: Compreender os sentidos que bioeticistas brasileiros atribuem aos princípios da universalidade e da integralidade no sistema público de saúde brasileiro. PROCEDIMENTOS METODOLÓGICOS: Estudo exploratório qualitativo, realizado com 20 professores universitários de bioética atuantes no campo das ciências da saúde, com funções de diretores e ex-diretores da Sociedade Brasileira de Bioética e de diretorias regionais, no período de julho de 2007 a julho de 2008. Foram realizadas entrevistas semi-estruturadas, com perguntas abertas, sendo realizada análise de conteúdo. ANÁLISE DE RESULTADOS: Quanto ao princípio da universalidade de acesso dos cidadãos brasileiros a um sistema público, as manifestações dos entrevistados se posicionaram majoritariamente em prol de sua manutenção. Todavia, quanto ao princípio da integralidade, as divergências foram manifestas, ensejando a maioria em restringi-lo. CONCLUSÕES: Os bioeticistas relatam pluralismo de valores morais e dificuldades em decidir moralmente sobre o que seria um sistema de saúde justo
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Certification of an ISO 14001 Environmental Management System (EMS) is currently an important requirement for those enterprises wishing to sell their products in the context of a global market. The system`s structure is based on environmental impact evaluation (EIE). However, if an erroneous or inadequate methodology is applied, the entire process may be jeopardized. Many methodologies have been developed for making of EIEs, some of them are fairly complex and unsuitable for EMS implementation in an organizational context, principally when small and medium size enterprises (SMEs) are involved. The proposed methodology for EIE is part of a model for implementing EMS. The methodological approach used was a qualitative exploratory research method based upon sources of evidence such as document analyses, semi-structured interviews and participant observations. By adopting a cooperative implementation model based on the theory of system engineering, difficulties relating to implementation of the sub-system were overcome thus encouraging SMEs to implement EMS. (C) 2007 Elsevier Ltd. All rights reserved.