Abstract Authors:   Ekman, Felix 890924                Henriksson, Richard 880325 Tutor:    <img src="file:///page3image1648" />   Prof. Anders Pehrsson Examiner: Ass. Prof. Sarah Philipson Title:         Explanatory Factors of Perceived Expansion Barriers Introduction: A characteristic of the twenty first century business environment is the increased globalisation. Due to the globalisation, it has become necessary for organizations to be involved in international business, and the globalisation of the marketplace in general has increased the export. When expanding to international markets, companies might face some obstacles and barriers, which makes it an important topic in the research field of international marketing and strategy. Since most research focuses just on the importance of the expansion barriers, it would be of importance to provide empirical evidence on what types of explanatory factors that are associated with firms’ perception of expansion barriers. Purpose: Gain an understanding of different explanatory factors regarding expansion barriers for companies’ expansion on international markets. Methodology: The research approach was quantitative with mainly primary data, which was collected through a questionnaire distributed through e-mail. The sample frame was Swedish companies that exporting goods to Norway, Poland, Russia and/or the Baltic region. A total of 157 completed questionnaires, response rate of 20%, were collected and was the foundation for the analysis and results. Conclusion: The explanatory factors that are associated with the perception of expansion barriers were; Geographical and Cultural distances, Market experience and Institutional collaborations. The fourth explanatory factor, intermediating strategy, has in this study no association to the perception of the barriers. Keywords: Expansion Barriers, Explanatory Factors, International Marketing Strategy.

Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis. This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers. In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers. In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7. We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67. DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors. None of the investigated markers in study III and IV correlated with disease free survival or overall survival. In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.

A complex network of transcription factors, which are regulated by signalling molecules, is responsible in coordinating the formation of differentiated skeletal and cardiac myocytes from undifferentiated stem cells. The present study aims to understand and compare the transcriptional regulation of skeletal and/or cardiac muscle development in the absence of Sox7 or in the presence of a collagen-based matrix in P19 embyonal carcinoma (EC) and mouse embryonic stem (ES) cells. First, knock-down of Sox7 , by shRNA, in muscle inducing conditions (+DMSO) and in the absence of RA (-RA), decreased muscle progenitor transcription factor and myogenic regulatory factor (MRF) levels, suggesting that Sox7 is necessary for myogenesis. However, knock-down of Sox7 in the presence of RA (+RA) and DMSO increased expression of muscle progenitor markers and MRFs, suggesting that Sox7 is inhibitory for myogenesis +RA. Furthermore, Sox7 overexpression enhanced myogenesis -RA, but inhibited myogenesis and enhanced neurogenesis +RA. These results suggest an important interplay between RA signalling and Sox7 function during P19 differentiation. Second, Q-PCR analysis showed that compared to the mouse ES cells differentiated on the regular TC plates, differentiation on the collagen matrices had a higher expression of skeletal and cardiac precursors, MRFs and terminal differentiation markers. Collagen alone enhanced myotube formation. The enhanced collagen matrix, containing the oligosaccharide sialyl LewisX (sLeX), specifically enhanced cardiomyogenesis. These studies have added to our understanding of the transcriptional regulation of premyogenic mesoderm factors and the role of Sox7 in this process. In addition these studies provide a vision for possible use of biomaterials in directed differentiation of stem cells for the purpose of cell therapy.

The formation of neural connections in the mammalian nervous system is a complex process. During development, axons are initially overproduced and compete for limited quantities of target-derived growth factors. Axons which participate in functional circuits and secure appropriate amounts of growth factors are stabilized, while those axons that are either inappropriately connected or do not obtain sufficient concentrations of growth factors are eliminated in a process termed ‘axon pruning’. In this thesis, I examined the mechanisms that regulate pruning of peripheral, NGF-dependent sympathetic neurons that project to the eye. I determined that pruning of these projections in vivo requires the p75 neurotrophin receptor (p75NTR) and synthesis of brain-derived neurotrophic factor (BDNF) from the activity-dependent exon IV promoter. Furthermore, analysis of an in vitro model of axon competition, which is regulated by the interplay between nerve growth factor (NGF) and neuronal activity, revealed that p75NTR and BDNF are also essential for axon competition in culture. In this model, in the presence of NGF, neural activity confers a competitive growth advantage to stimulated, active axons by enhancing downstream TrkA (NGF receptor) signaling locally in axons. More interestingly, the unstimulated, inactive axons deriving from the same and neighboring neurons acquire a "growth disadvantage" due to secreted BDNF acting through p75NTR, which induces axon degeneration by suppressing TrkA signaling that is essential for axonal integrity. These data support a model where, during developmental axon competition, successful axons secrete BDNF in an activity-dependent fashion which activates p75NTR on unsuccessful neighboring axons, suppressing TrkA signaling, and ultimately promoting pruning by a degenerative mechanism.

In contrast to cardiac rehabilitation (CR) programs, traditional stroke rehabilitation aims to maximize functional independence and does not have a strong focus on exercise training and risk factor modification. Given the parallels between stroke and heart disease in cardiovascular etiology and risk factors, CR may be suited to supplement stroke rehabilitation by providing opportunities to enhance fitness and manage stroke risk factors. The aim of this work was to 1) examine the use of a non-adapted CR program of care with individuals with stroke and/or transient ischemic attack (TIA) through a retrospective database review, 2) using a prospective trial, determine the feasibility and effects of an adapted CR program for people with mild to moderate impairment from stroke, and 3) explore characteristics related to degree of program response in aerobic and functional capacity through secondary data analysis. The results from Study 1 demonstrated that traditional CR is an underutilized service for individuals with stroke or TIA, yet improvements in aerobic fitness were comparable to their non-stroke counterparts. In Study 2, adapted CR was feasible for individuals with a range of stroke-related disability and effective in increasing aerobic capacity. The anticipated carry over to improved walking capacity was not observed. There were no changes in health-related quality of life or stroke risk factors. Study 3 identified subgroups of participants who improved or declined in aerobic and ambulatory capacity after the adapted CR program. There were no differences in baseline characteristics, indices of time, intensity or volume of exercise performed across the response subgroups. In summary, given the parallels between stroke and heart disease, the needs of the stroke population and dearth of community-based exercise programming available for them, the CR model of care may be applied for individuals with stroke to provide opportunities for exercise training and risk factor modification.

A pilot study was conducted to evaluate whether premenstrual syndrome was a risk factor for breast cancer among premenopausal women. As subjects, 54 women between the ages of 26 and 46 years, each diagnosed with breast cancer, were compared to three separate control groups, consisting of 193 female patients seen in medical offices for routine physical exams, 51 female nursing students, and 559 female graduate students. Each eligible subject was either mailed or personally given a survey questionnaire probing premenstrual and menstrual symptomatology and general descriptive characteristics. An association between premenstrual syndrome and breast cancer was evaluated by estimating exposure odds ratios and associated confidence intervals. Analysis of the data suggested that premenstrual syndrome did not pose a breast cancer risk among premenopausal women. / Graduation date: 1993

Statistics Canada data indicates that between 2002 and 2006, the late stillbirth incidence (at or beyond 28 weeks gestation) was 3.0/1000 and 4.0/1000 among Canadian and Saskatchewan births respectively. This difference questions the characteristics and associations of late losses in our province; this work aims to assess late Saskatchewan stillbirths in regard to incidence, causes, characteristics, and area-level factors.<p> Accessing Vital Statistics cases (1987 to 2007, n=1119), descriptive statistics and incidence were examined utilizing Chi-square testing and Poisson regression. Associations between variables were evaluated by log-linear models. Area-level factors relating to incidence within census divisions were explored using Poisson regression.<p> Although some variation existed by time and region, women were most often less than 35 years, of moderate parity, non-Aboriginal, had no previous stillbirths, and were not carrying multiple fetuses. Approximately half of the losses were preterm and half were inadequately grown. Incidence per 1000 births differed significantly for Saskatchewan (3.86) and Canada (3.43) with only Canada declining. Several division values were also higher than Saskatoons Division 11. Associations were seen between characteristics; most notably the combination of Aboriginality, increased maternal age, and large-for-gestational-age appeared over-represented compared to live births. Regions with higher proportions of Aboriginal preschoolers or land area with herbicide application had higher incidence (RR = 1.53 and 1.55, p-value less than 0.001). Further work is required to understand Saskatchewans lack of decline, what can be done about areas where incidence is increased, the significance of the associated characteristics as actual risk factors, and how Aboriginality and herbicide influence risk at the individual level.

The Arabidopsis TGA family of basic leucine zipper transcription factors regulate the expression of pathogenesis-related genes and are required for resistance to disease. Members of the family possess diverse properties in respect to their ability to transactivate and interact with NPR1, the central regulator of systemic acquired resistance in Arabidopsis. Two TGA factors, TGA1 and TGA2, have 83 % amino acid similarity but possess differing properties. TGA1 does not interact with NPR1 but is able to transactivate, while TGA2 interacts with NPR1 but is unable to transactivate. This study uses these two TGA factors to identify amino acids that are responsible for their function. <p>Four cysteines residues within TGA1 were targeted for study by site-directed mutagenesis and the resulting mutants were tested for interaction with NPR1 in yeast. The construct containing a mutation of cysteine 260 (Cys-260) interacted well with NPR1, while those with mutations at Cys-172 or Cys-266 interacted poorly. The Cys-260 mutant also displayed the greatest decrease in transactivation potential in yeast, while mutation of Cys-172 or Cys-266 resulted in smaller decreases. Mutation of Cys-287 had no effect on NPR1 interaction or transactivation. Combining various point mutations in a single protein did not increase NPR1 interaction or transactivation levels, indicating that Cys-260 is crucial for regulating TGA1 properties. Cysteines possess the unique ability of forming reversible disulfide bonds which have been shown to regulate several mammalian cellular processes. The observation that mutation of a single TGA1 cysteine (Cys-260) greatly alters the proteins properties provides a convincing argument that oxidoreduction of this residue is important for its regulation, possibly through the formation of a disulfide bond with either Cys-172 or Cys-266. <p>To test whether other members of the TGA family could be regulated by oxidoreduction, several TGA2 constructs were created that introduced Cys at positions corresponding to those found in TGA1. When tested in yeast none were able to transactivate but continued to interact with NPR1.

Few studies examine technical barriers, such as usability, to successful Computerized Provider Order Entry (CPOE) system implementation. This thesis explores this literature gap through the evaluation of the Sunnybrook CPOE order set system with a heuristic evaluation of the Sunnybrook CPOE system, the development of a more user friendly CPOE order set interface (Test Design), and a usability study comparing three order set formats (Sunnybrook CPOE, Test Design, and paper order sets). A randomized trial was conducted with 27 Sunnybrook physicians at the hospital. Results showed that the Sunnybrook CPOE order set system was less efficient (task times were on average 364 seconds longer than Test Design and 344 seconds longer than paper), less user-friendly (users were less confident, less satisfied, and more frustrated with Sunnybrook CPOE tasks), and less safe than paper order sets (more harmful errors). Test Design was as efficient and safe as paper order sets.

Few studies examine technical barriers, such as usability, to successful Computerized Provider Order Entry (CPOE) system implementation. This thesis explores this literature gap through the evaluation of the Sunnybrook CPOE order set system with a heuristic evaluation of the Sunnybrook CPOE system, the development of a more user friendly CPOE order set interface (Test Design), and a usability study comparing three order set formats (Sunnybrook CPOE, Test Design, and paper order sets). A randomized trial was conducted with 27 Sunnybrook physicians at the hospital. Results showed that the Sunnybrook CPOE order set system was less efficient (task times were on average 364 seconds longer than Test Design and 344 seconds longer than paper), less user-friendly (users were less confident, less satisfied, and more frustrated with Sunnybrook CPOE tasks), and less safe than paper order sets (more harmful errors). Test Design was as efficient and safe as paper order sets.