One of the key concepts within the marketing literature remains the 'marketing mix.' An unexamined element of this mix remains, to pursue the cooking metaphor, the way in which the chef is able to balance the various ingredients to achieve a palatable dish. Therefore, the impetus behind this thesis is this lack in the literature. The approach to remedy this lack is developed through Action Research. The original notion of the marketer as a mixer of ingredients strongly suggests that marketing was (and remains) largely a craft. As practitioners within the craft, managers require devices to guide them in their everyday operations. However, the use and effectiveness of such 'heuristic devices' by practising marketers remains little explored. Matrix schemas have always been traditionally used, by both academics and practitioners, in the development and interpretation of both strategy and tactics in marketing. While the strategic schemas have attained the status of dogma (the Boston Box, for example), at the tactical level,use of the marketing mix has never reached such heights, (apart from an occasional stress on the need for the 'blending of ingredients'). As marketing has developed as a craft, numerous definitions have been offered. Today there are several different authoritative, but accepted definitions. The Chartered Institute of Marketing [CIM] and the American Marketing Association [AMA] define marketing as: 'Marketing [management] is the process of planning and executing the conception of pricing, promotion, and distribution of ideas, goods and services that satisfy organisational objectives.' [Fifield & Gilligan, 1996; 2] A clear understanding of the development of the matrix approach from the level of strategy to tactics in marketing is the essence of the published works. The marketing mix concept seems relatively simple. Since Culliton [1947] first carried out his study (amongst the major American companies of his time), the notion of managers within the marketing function as 'mixers of ingredients' has enjoyed wide currency. Culliton's study included a full examination of a number of case histories and the use by the participating companies of marketing ingredients. Borden [1964] expanded this work to a formal use of the term 'marketing mix' and he presented a list of mix constituents, based on Culliton's work. These developments were taken further by McCarthy [1964] in terms of simplification and classificatory order as the famous 4Ps. It is now just over 30 years since McCarthy provided this gloss on Borden's work and offered a generic marketing mix [product, price, promotion and place] as a means of translating marketing planning and tactics into practice [Bennett 1997:151] This eventually led to Kotler [2000) defining the mix as being 'A set of marketing tools that a firm uses to pursue its objectives.' Thus, ingredients become tools and the analogy changes. McCarthy's 4Ps classification of the marketing mix variables has received acceptance in past decades. However, in recent years increasing criticism of this approach has been voiced in academic circles (Van Waterschoot, 1992, p.83). It is believed by some academics that this paradigm is beginning to lose its position (Gronroos, 1994, Gronroos, 1992, Sheth 1988). It is sometimes called 'traditional' or out-dated (Shimpock-Viewg,/1993, Lane, /1988, Turnbull, 1987). Over the past few years, it has been argued that marketing is concerned not just with the original 4Ps and the various elements associated with them, but also with less controllable variables (or ingredients, or tools) such as people, processes and service evidence. (Rafiq, 1995). However, the shifts from 'ingredients' to 'tools' to 'variables' hints at an underlying confusion as to the conceptual status of the artefacts described. Borden's work has the merit that his classificatory schema derives directly from empirical evidence. Borden reflected this basis when he identified the need to record within case studies evidence of what was being mixed in the marketing domain. Later extensions do not, by and large, have this merit. There have been no published studies which replicate Culliton's original work. Extensions to the mix (the conceptual device contributed by Borden) and the distilled formulation of the mix offered by McCarthy rely on conceptual processes only. The nature of the extensions seems clear, but they rest on different assumptions about how the world of the marketing manager should be construed. This thesis draws on several case studies of the world of marketing managers and a test of the 4P's framework within that world as its modus operandi. The examination uses a process of 'Action Research'. It thus is placed in the tradition established by Culliton in his pioneering work. Unlike Culliton, the work does no flow from a considered execution of a single research design, but has emerged in the search for consistency in marketing management, as pursued with the manager themselves. In essence, the Action Learning method of research has been adopted. The outcome, a new model for application, is seen as the contribution to knowledge. In essence the thesis pulls together the understanding and criticisms that both practitioners and academics need to investigate the gaps that exist in marketing management research. The importance of a company's participation as being integral to the action it takes and the solutions it prescribes is the essence of the Action Research and the model process.

This study had two aspects. The first was the production and purification of TIMP-l. The second was a series of biophysical studies of TIMP-l and a TIMP-l derived peptide. A monoclonal antibody affinity column was developed and used to purifY large quantities of human TIMP-l for further experiments. Two E.coli expression systems were studied to determine whether they would be suitable for large scale production of recombinant protein. In the first system TIMP-I was to be secreted as a fusion protein which could be cleaved, leaving a free N-terminus. It was discovered that it was not possible to cleave off the fusion protein. In the second system, the protein was secreted, without additions to the periplasm. Although active protein, with the correct N-tenninus, was obtained, the yields were too low to be of use for large scale expression. Secondary structure analysis by CD and FTIR showed TIMP-l to be a mostly f3- sheet protein (approaching 50%) with around 20% a-helix. A temperature study using these techniques found that little change occurs until temperatures of over 60°C where the protein aggregates. The small changes appear to be a general loosening of the structure. In analyses of the surface of TIMP-l, additional carbohydrate was identified (other than the two N-linked chains) using Con-A probing of Western blots. TIMP-l purified from WI-38 foetal lung fibroblast cells can be separated into two pools by Concanavalin A-Sepharose chromatography. These two pools were found to have a different set of pIs and a different monosaccharide composition. The use of NMR paramagnetic probes identified a hydrophobic region exposed on the surface of TIMP-I. This region probably includes a tyrosine residue and either a tryptophan or phenylalanine. The presence of an exposed hydrophobic region was also shown in binding studies using the fluorescent probe ANS. These studies identified a single, low affinity binding site. An additional study with the N-terminal fragment of type-I collagenase found no binding sites on the enzyme, but a change in fluorescence occurred when TIMP-I was present. A peptide was designed based on the N-terminal sequence of TIMP-I. High homology, susceptibility to mutation and an interesting resemblance to the Bowman-Birk family of inhibitors suggested that this peptide might be inhibitory. It was found to have only a weak inhibitory activity against gelatinase. NMR studies of this peptide in water showed a large number of conformers as a result of stabilisation of the cis isomer of its proline residues. This preference for the cis form was retained for one proline in the solvent, TFE. Preliminary NMR studies were also carried out which concluded that TIMP-I should be suitable for further structural studies using isotopic labelling.

In this dissertation we study the Lyapunov diagonal stability and its extensions through partitions of the index set {1,...,n}. This type of matrix stability plays an important role in various applied areas such as population dynamics, systems theory and complex networks. We first examine a result of Redheffer that reduces Lyapunov diagonal stability of a matrix to common diagonal Lyapunov solutions on two matrices of order one less. An enhanced statement of this result based on the Schur complement formulation is presented here along with a shorter and purely matrix-theoretic proof. We develop a number of extensions to this result, and formulate the range of feasible common diagonal Lyapunov solutions. In particular, we derive explicit algebraic conditions for a set of 2 x 2 matrices to share a common diagonal Lyapunov solution. In addition, we provide an affirmative answer to an open problem concerning two different necessary and sufficient conditions, due to Oleng, Narendra, and Shorten, for a pair of 2 x 2 matrices to share a common diagonal Lyapunov solution. Furthermore, the connection between Lyapunov diagonal stability and the P-matrix property under certain Hadamard multiplication is extended. Accordingly, we present a new characterization involving Hadamard multiplications for simultaneous Lyapunov diagonal stability on a set of matrices. In particular, the common diagonal Lyapunov solution problem is reduced to a more convenient determinantal condition. This development is based upon a new concept called P-sets and a recent result regarding simultaneous Lyapunov diagonal stability by Berman, Goldberg, and Shorten. Next, we consider various types of matrix stability involving a partition alpha of {1,..., n}. We introduce the notions of additive H(alpha)-stability and P_0(alpha)-matrices, extending those of additive D-stability and nonsingular P_0-matrices. Several new results are developed, connecting additive H(alpha)-stability and the P_0(alpha)-matrix property to the existing results on matrix stability involving alpha. We also point out some differences between these types of matrix stability and the conventional matrix stability. Besides, the extensions of results related to Lyapunov diagonal stability, D-stability, and additive D-stability are discussed. Finally, we introduce the notion of common alpha-scalar diagonal Lyapunov solutions over a set of matrices, which is a generalization of common diagonal Lyapunov solutions. We present two different characterizations of this new concept based on the well-known results for Lyapunov alpha-scalar stability [34]. The first one hinges on a general version of the theorem of the alternative, and the second one using Hadamard multiplications stems from an extension of the P-set property. Several illustrative examples and an application concerning a set of block upper triangular matrices are provided.

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Orientador: Ana Paula de Souza Pardo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-15T12:46:18Z (GMT). No. of bitstreams: 1 Planello_AlineCristiane_M.pdf: 940083 bytes, checksum: 36ed3b0b3b0d10c144805116e08917dd (MD5) Previous issue date: 2010 / Resumo: Objetivo: As Metaloproteinases da Matriz ( MMPs) são enzimas que degradam a matriz extracelular (MEC) e tem sido associadas às desordens temporomandibulares (DTM). Nós investigamos a freqüência dos -1607 1G/2G MMP1 polimorfismo (rs1799750), -1171 6A/5A MMP3 polimorfismo (rs3025058) e -1562 C/T MMP9 polimorfismo (rs3918242) em indivíduos com sinais de degeneração da ATM, diagnosticados por exame de imagem, a fim de analisar a associação desses polimorfismos e a DTM. Métodos: A população estudada foi composta por 115 indivíduos diagnosticados por exame de imagem (grupo DTM) e 117 controles. Os polimorfismos genéticos foram determinados por PCR/RFLP. Resultados: A freqüência do genótipo 2G/2G no gene MMP1 foi significantemente mais alta no grupo DTM do que no grupo Controle (p = 0.008). O genótipo 2G/2G no grupo DTM mostrou um risco aumentado para a DTM com um OR = 2.25 ( 95% IC = 1.26 - 3.99) quando comparado com os genótipo 1G/2G e 1G/1G. A freqüência dos alelos do gene MMP1 não mostrou diferença significativa entre os grupos (p > 0.05). A distribuição dos genótipos e alelos dos genes MMP3 e MMP9 não mostrou diferença significativa (p > 0.05). Conclusão: Nossos resultados mostram a associação entre o polimorfismo -1607 MMP1 e a suscetibilidade à DTM / Abstract: Objective. Matrix metalloproteinases (MMPs) degrade extracellular matrix components and have been implicated to play an important role in temporomandibular joint disorder (TMD). We investigated the frequency of -1607 1G/2G MMP1 polymorphism (rs1799750), -1171 6A/5A MMP3 polymorphism (rs3025058) and -1562 C/T MMP9 polymorphism (rs3918242) in individuals with TMJ degeneration diagnosed by image exam in order to analyze the association of these MMPs polymorphisms and TMD. Methods. The studied population comprised 115 TMD individuals diagnosed by image exam and 117 healthy controls. Genotypes were determined using polymerase chain reaction/Restriction fragment length polymorphism PCR/RFLP. Results. The MMP1 2G/2G genotype was significantly higher in the TMD group than in the Control group (p = 0.008). The genotype 2G/2G in the TMD group showed an increased risk to TMD with an OR = 2.25 (95% CI = 1.26 - 3.99) when compared with 1G/2G and 1G/1G genotypes. Analysis of MMP1 allele frequencies showed no significant difference (p > 0.05). The MMP3 and MMP9 genotypes distribution and alleles frequency did not differ between the groups (p > 0.05). Conclusion. Our results report the association of -1607 MMP1 gene polymorphism and increased risk to TMD / Mestrado / Histologia e Embriologia / Mestre em Biologia Buco-Dental

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No description available.

LTBP-1 is a large extracellular glycoprotein that is a component of the large latent TGF-β complex. The extracellular sequestration of latent TGF-β in the extracellular matrix (ECM) is fundamental to the regulation of TGF-β bioavailability and activity. LTBP-1 is described to contribute to the regulation of TGF-β bioavailability through mediating the extracellular sequestration of newly secreted latent TGF-β with fibrillin microfibrils in the ECM. However it is not well understood how LTBP-1, and thus latent TGF-β, becomes deposited into the ECM. Previous work by our group suggested that LTBP-1 interactions with the glycosaminoglycan heparan sulphate (HS) at the cell-matrix interface might facilitate the association of LTBP-1 with fibrillin microfibrils. Using recombinant LTBP-1 fragments and mutants, LTBP-1 interaction with HS have been fine-mapped. Deposition of a LTBP-1 HS-binding mutant, and of LTBP-1 when HS was depleted, was studied in cell cultures; findings presented here demonstrate that HS may not be critical for the deposition of LTBP-1 into the ECM. Contributions of fibrillin and fibronectin to LTBP-1 deposition were investigated, and data presented here support published findings that fibrillin is not always required for LTBP-1 deposition. In addition, the dependency of LTBP-1 deposition upon fibronectin was suggested to differ between different cell types (epithelial and mesenchymal). How LTBP-1 may be stabilised within the ECM through crosslinking by tissue transglutaminase was investigated using recombinant fragments and cell culture studies. Tissue transglutaminase was found to promote the extracellular incorporation of LTBP-1, and novel cross-links within LTBP-1, and between LTBP-1 and fibrillin-1, but not LTBP-1 and fibronectin, were identified. Additionally, results indicated that LTBP-1 was present in extremely high molecular weight assemblies in the ECM of cultured fibroblasts. Collectively, these results have contributed to current knowledge of how LTBP-1 becomes deposited into the ECM. They indicate that the deposition of LTBP-1 is not underpinned by HS, may be cell type-specific, and that LTBP-1 may potentially self-assemble extracellularly into homotypic structures that may associate with fibrillin microfibrils.

Aim: Microbial biofilm matrix contains polysaccharides and proteins and can require extracellular nucleic acids for initial formation. Experiments were designed to identify infectious pathogens in human aneurysms and to characterize biofilm formed by calcified human arterial-derived nanoparticles. Materials & method: A total of 26 different microbial pathogens were isolated from 48 inflammatory aneurysms. Consistent amounts (0.49 McFarland units) of nanoparticles derived from similar tissue were seeded into 24-well plates and cultured for 21 days in the absence (control) or presence of RNase, tetracycline or gentamicin. Results: Control biofilm developed within 14 days, as detected by concanavalin A and BacLight™ Green staining. The formation of biofilm in wells treated with RNase was not different from the control; however, gentamicin partially inhibited and tetracycline completely inhibited biofilm formation. Therefore, nanoparticle biofilm retains some characteristics of conventional bacterial biofilm and requires protein-calcium interactions, although extracellular RNA is not required. Conclusion: This model system may also allow study of nanosized vesicles derived from donor tissue, including any microbes present, and could provide a useful tool for in vitro investigation of nanoparticle biofilm formation.

The aim of the research was to investigate the factors to be considered in the adoption of the matrix management organization structure within State-Owned Enterprises. It also investigated how the employees understand the project matrix management organization structure and its application, how they observe it to be and whether their misunderstanding of their roles in the structure will have an impact on meeting the project objectives and performance. This research also investigated whether the utilization of the project matrix management organization structure promotes the successful completion of project or whether it delays the project. The problem examined was “the State-Owned enterprise is still experiencing problems meeting project objectives despite implementing the matrix management organization structure which was intended to facilitate the meeting of project objectives within the organization”. The misunderstanding on the roles and functions of personnel within a project environment using the matrix organization structure was also investigated on whether it has an impact on meeting project objectives and performance. The research question for this study was: “What are the factors that hinder or support the State-Owned Enterprise with the adoption of the matrix management organization structure to meet its project objectives?” The research paradigm was interpretivist. The strategy used was empirical, with an inductive approach. The study approach was qualitative with a survey questionnaire and semi-structured interviews as data collection methods and the data analysis was thematic. The following were the key findings of the study: In terms of awareness of the structure, most respondents advised that the organisation is using a project matrix management organisation structure. The enablers that were agreed on are managing complexity, resource efficiency, communication effectiveness and output quality. The barriers that were agreed on were ambiguous authority and dual reporting, decision-making delays, management of cross-functional teams, lack of a matrix guardian and level of conflicts. The indication in terms of cost performance was that the projects had cost implications. Most projects were completed on budget with 51% indicating that the projects had an overspend. 74% indicated that the projects that they have worked on were completed behind schedule. 16% indicated that the projects were completed on time. The perception is that this type of structure, due to the number of the managers that are involved lacks decision making. The lack of decision making is caused by lack of communication and stakeholder engagement. Stakeholder engagement was also an issue that was highlighted as lacking.