Evidence exists that epidermal growth factor (EGF) and alpha transforming growth factor (αTGF) are important in breast cancer. An inverse relationship between epidermal growth factor receptor (EGF-R) and oestrogen receptor (ER) has been reported by some, (1) but not all workers (2). The aim in this thesis was to develop assays to measure, levels of EGF, and determine EGF-R status in human breast tumours. These results were then correlated with each other, with ER and node status and histological grade (Bloom & Richardson). An additional aim in this thesis was to develop a source of αTGF in conditioned median (CM) from a transformed cell line. After extraction and purification, the αTGF was intended for use as an immunogen to produce a polyclonal antiserum which could be used in either an RIA or ELISA. EGF was measured by a radioimmunoassay (RIA) utilising a rabbit antimouse EGF antiserum. This assay (sensitivity 0.1ng/ml) was demonstrated to have no cross reactivity with αTGF. The EGF-R assay was similar to that described by Sainsbury. (1) In a series of 88 human breast tumours 47 (53.4%) were found to contain extractable EGF. Forty eight (54.5%) were EGF-R positive and 39 (44.3%) were ER positive. A direct relationship between EGF and ER+ ve status was found (p < 0.01). Significantly higher levels of EGF were extracted from ER+ ve tumours (p = 0.049) compared with that from ER-ve tumours. However no relationship between EGF-R and EGF or ER status was found, or between EGF levels and histological grade or node status. A suitable cell line which produced αTGF, was obtained and culture conditions optimised. Alpha-TGF was assayed by a radioreceptor assay which utilised a cell line rich in EGF-R (A431). Extraction of αTGF was based on the principles of molecular grading by gel filtration (Sephadex G50), and ion exchange (Sephadex CM C25). By this process the αTGF was purified and separated it from any EGF present. By this method 20μg of αTGF was produced from 61t of CM. 1) Sainsbury JRC, Farndon JR, Serbet GV, Harris AL. Epidermal-growth-factor-receptors and oestrogen receptors in human breast cancer. Lancet 1985; <i>1</i>: 364-368. 2) Fitzpatrick SL, Brightwell J, Wattliff JL, Barrows GH, Schultz GS. Epidermal growth factor binding by breast tumour biopsies and relationship to oestrogen receptor and progestin receptor levels. Cancer Res 1984; <i>44</i>: 3448-3453.

The purpose of this thesis is to understand the applications and limitations of the Climatological Dispersion Model (CDM), and to explain the role of dispersion modeling within the framework of urban and regional planning. In order to reach the first objective, a detailed study study of the mechanics of the CDM was conducted. Completion of this task provided the necessary foundation for a discussion of the assets and limitations of the model. Conclusions and recommendations are made concerning the utility of the CDM for an urban area.The second objective focuses on the practical applications of dispersion modeling and is divided into four areas; the role of dispersion modeling in air quality management, the practical applications of dispersion modeling from a community view, the incorporation of dispersion modeling into the planning process, and the effectiveness and future direction of dispersion modeling. / Department of Urban Planning

Abstract Keywords Market entry timing, associating factors Background Market entry timing is an important concept that influences the success of firms in international business. Companies earn big profits due to their perfect market entry timing. In contrast, McKinsey 2005 report showed that for every successful entry, there are four failures. On the other hand, the academic world also pays attention to entry timing by investigating its associating factors. Since there are gaps in academic research together with the need for deeper understanding, this thesis is dedicated to market entry timing. Purpose The purpose is to understand associating factors and their relation to foreign market entry timing. Method This study is a multiple case study exploratory research analysed through pattern finding for qualitative research. Semi-structured in-depth interviews were conducted with four companies. Conclusion There are nine factors associating with entry timing decisions: home and host country characteristics, firm capabilities and characteristics, competition, cultural distance, economic factors, Window of Opportunity, Word-of-Mouth, Stepwise internationalization, near-market knowledge. The research focuses on the last four factors and their influence in entry timing were discovered. Window of Opportunity can be perceived as “right business connections” and companies tend to enter foreign markets once they find the right business connection. Word of Mouth has an impact on entry timing in the situation that firms can be prompted to enter foreign market when positive Word of Mouth effect existed. Stepwise internationalization is the choice of firms, whose entry timing would be slower than other options. Near-market knowledge of the economic system can be transferred between countries that firms operate in and firms will be likely to enter market when they gain necessary knowledge of a similar economic system.

The fibroblast growth factor family of polypeptides currently consists of nine structurally-related members. Cloning of the mouse homologue of the latest reported member of the family, FGF-9, is described in this study. Mouse Fgf9 exhibits a high level of sequence conservation with the human, rat and Xenopus counterparts. Of note is the lack of a hydrophobic signal peptide at the N-terminus of the coding sequence. The protein, however, appeared to be secreted by producer cells since a significant quantity of the protein could be purified from the culture supernatant of transfected cells. Members of the FGF family are known to bind to cell surface tyrosine kinase receptors (FGFRs) to elicit a variety of physiological responses. These receptors themselves form a family of four structurally-related tyrosine kinases and each FGF member commonly has the ability to bind several members of the FGFR family. By using in vitro plate binding assays, FGF-9 is shown in this study to bind specifically to two FGFR members: FGFR2b and FGFR3c. To further study the potential functional role of FGF-9, its expression pattern in the mouse embryo was examined by both RNase protection and RNA in situ hybridization analyses. The transcript was detected in a variety of embryonic tissues: the germinal epithelium of the central nervous system, the mesonephric cords, the somites, the gut primordia and the developing eye and ear, suggesting that the gene may have multiple roles during development. In addition, the potential involvement of FGF-9 in mediating adult brain functions was examined by double RNA in situ hybridization analysis of the distribution of both Fgf9 and Fgfr3 transcripts in the adult mouse brain. Most apparent areas of co-localization are the olfactory bulb and cerebral cortex. The two transcripts are also shown to have distinct distribution patterns in the cerebellum.

The macrophage (Mφ) foam cell in the atherosclerotic plaque microenvironment is subjected to cytokines and growth factors secreted by smooth muscle cells (SMCs), endothelial cells (ECs), platelets and lesional Mφ themselves. This thesis examines the effects of some of these soluble factors on a murine macrophage membrane molecule, the macrophage scavenger receptor (MSR), considered pivotal in foam cell formation and atherogenesis. Macrophage Colony-stimulating factor (MCSF) enhances MSR expression and functional activity (including MSR-dependent adhesion) in elicited peritoneal Mφ markedly and selectively. The T lymphocyte products, Th1 (interferon-gamma(IFN-γ)) and Th2 (chiefly interleukin-4 (IL-4)) cytokines, have divergent effects with IL-4 upregulating and IFN-γ either maintaining or downregulating MSR status. IL-4 induced MSR microheterogeneity is due to changes in N-linked glycosylation, specifically sialylation and may be physiologically significant. In contrast to interleukin-10 (IL-10), transforming growth factor-beta (TGF-β) inhibits MSR upregulation, also when produced endogenously. TGF-β is as potent an inhibitor of MSR function as M-CSF is a stimulator. A cleaved truncated soluble form of MSR which lacks the cytoplasmic domain is present, by immunochemical assays, in culture supernatants. M-CSF increases soluble MSR release in vitro which is functionally active. Following upregulation of MSR surface expression in transfected CHO cells by prolonged culture, a modest MSR-dependent contribution to adhesion becomes apparent. To determine a possible adhesionpromoting region in the MSR, the binding site of mAb 2F8 was mapped using a series of MSR truncation mutants, and localized to residues 183 to 197 in the proximal cchelical coiled-coil domain. Morphological evidence, obtained by confocal and electron microscopy, supports an adhesion role for the MSR in primary Mφ and transfected CHO cells. MSR expression is prominently directed to the adherent surface and its distribution is restricted to cellular contact areas with the substratum. Organs and atherosclerotic lesions from mice deficient in M-CSF (osteopetrotic) and apolipoprotein E were examined to determine the effects of M-CSF on Mφ phenotype (including MSR expression) and lesion development in vivo. Though severely hypercholesterolemic, doubly deficient mice are protected against atherosclerosis and exhibit fewer Mφ and low MSR expression on remaining M-CSF independent populations. Prominent hepatic lipid accumulation suggests a crucial M-CSF dependent role for Kupffer cells in lipoprotein uptake, transfer to hepatocytes and biliary excretion of cholesterol. Regulation of MSR activity may therefore be important for the recruitment of Mφ into the arterial wall and, at the post-endothelial stage, to anchor Mφ at specific locations, thus favouring foam cell formation.

Background: Immunization is said to be the most effective public health intervention to prevent morbidity, complications, and mortality due to infectious disease among children. Due to the importance of vaccination in terms of infectious disease prevention, in terms of high cost-effectiveness ratio, international organizations, governments, and donors have intensified efforts to increase immunization coverage globally. Despite the efforts, thousands of children remain unimmunized or not fully vaccinated worldwide. Objective: To identify factors associated with incomplete immunization among children in Côte d’Ivoire. Method:The 1998-1999 and 2011-2012 Côte d’Ivoire Demography and Health Survey (DHS) data were used in this study. The included 3878 children aged 12 to 59 months with 1326 children from 1998-1999 DHS, and 2552 children from 2011-2012 DHS. Descriptive analysis was performed. Spearman’s correlation coefficient was computed to examine the relationship between variables. Univariate analysis was performed to examine the association between the dependent variable (incomplete immunization) and each independent variable using logistic regression. Variables with a p-value less than .05 in the univariate analysis were included in the multivariate analysis. Multivariate analysis was performed to determine predictors of immunization status using logistic regression (stepwise method). Results: About 42.7% and 50.1% of Côte d’Ivoire were not fully immunized in 1998-1999 and 2011-2012, respectively. Child birth place, mothers’ access to media, mothers’ literacy, place of residence, and religion were the best predictors of incomplete immunization. Conclusion:Health authorities in Côte d’Ivoire should take into account these immunization status predictors in order to address the issue of incomplete immunization.

This study has examined the rate at which the seeds of certain species disappear from woodland soils, and whether the composition of the seed banks beneath stands of known age can be used to reveal management history. Associated with this is an investigation of the spatial distribution of the stored propagules. A question arises as to whether species with long lived seeds can survive as buried seed long enough to take advantage of the opening of the canopy and soil disturbance resulting from the falling of old trees. Given the great life span of most trees, this is a strategy open only to species with exceptionally long lived seed banks. One such species is Hypericum pulchrum, which, as the seed bank surveys carried out in this study show, can exist as viable seeds beneath woodlands of great age in the Tavistock Woodland Estate in Devon. Is this germination and reproduction on tree falls sufficient to maintain Hypericum in the seed bank indefinitely ? To answer this question, a computer model was developed to examine the effect of various parameters on the survival time of a Hypericum seed bank beneath a simulated woodland. The model allowed prediction of both the mean density of buried seeds in a unit area, and the development of pattern within the seed bank. Analysis of the simulation results established that the dispersal of Hypericum was insufficient to maintain a seed bank by a &quot;chain reaction&quot; of windthrown reinforcement. The implications of this are discussed with respect to pioneer species within both temperate and tropical forests.

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