220 resultados para degree of priority importance
Resumo:
Objectives This research explores the relationship between young firms, their growth orientation-intention and a range of relationships which can be seen to provide business support. Prior-work Research indicates that networks impact the firm’s ability to secure resources (Sirmon and Hitt 2003; Liao and Welsch. 2004; Hanlon and Saunders 2007). Networks have been evaluated in a number of ways ranging from simple counts to characteristics of their composition (Davidsson and Honig 2003), strength of relationships (Granovetter 1973) and network diversity (Carter et al 2003). By providing access to resources and knowledge (from start-up assistance and raising capital, (e.g. Smallbone et al, 2003), networks may assist in enabling continued persistence during those times where firms may experience resource constraints owing to firm growth (Baker and Nelson 2005). Approach The data used in this research was generated in the 2008 UK Federation of Small Businesses (FSB) survey. Over 1,000 of the firms responding were found to fall into the category of “young”, ((defined as firms under 4 years old). Firms were considered the unit of analysis with the entrepreneur being the chief spokesperson for the firm. Preliminary data analysis considered key demographic characteristics and industry classifications, comparing the FSB data with that of the UK government’s own (BERR) Small Business Surveys of 2007 and 2008, to establish some degree of representativeness of the respondents. The analysis then examined networks with varying potential ability to provide support for young firms, the networks measured in terms of number, diversity, characteristic and strength in its relationship to young firm growth orientation. The diversity of business-support-related relationships ranged from friends and family, through professional services, customers and suppliers, and government business services, to trade associations and informal business networks. The characteristics of these formal and informal sources of support for new businesses are examined across a range of business support-type activities for new firms. The number of relationships and types of business support are also explored. Finally, the strength of these relationships is examined by analysis of the source of business support, type of business support, and links to the growth orientation-intention of the firm, after controlling for a number of key variables related to firm and industry status and owner characteristics. Results Preliminary analysis of the data by means of univariate analysis showed that average number of sources of advice was around 2.5 (from a potential total of 6). In terms of the diversity of relationships, universities had by far the smallest percentage of firms receiving beneficial advice from them. Government business services were beneficially used by 40% of young firms, the other relationship types being around the 50-55% mark. In terms of characteristics of the advice, the average number of areas in which benefit was achieved was around 5.5 of a maximum of 15. Start-up advice has by far the highest percentage of firms obtaining beneficial advice, with increasing sales, improving contacts and improving confidence being the other categories at or around the 50% mark. Other market-focused areas where benefits were also received were in the areas of new markets, existing product improvements and new product improvements, where around 40% of the young responding firms obtained benefit. Regression techniques evaluating the strength of these relationships in terms of the links between business support (by source of support, type of support, and range of support) and firm growth orientation-intention focus highlighted a number of significant relationships, even after controlling for a range of other explanatory variables identified in the literature. Specifically, there was found to be a positive relationship between receiving business advice generally (regardless of type or source) and growth orientation. This relationship was seen to be stronger, however, when looking at the number of types of beneficial advice received, and stronger again for the number of sources of this advice. In terms of individual sources of advice, customers and suppliers had the strongest relationship with growth, with Government business services also found to be significant. Combining these two sources was also seen to increase the strength of the relationship between these two sources of advice and growth orientation. In considering areas of support, growth was most strongly positively related to advice that benefited the development of new products and services, and also business confidence, but was negatively related to advice linked to business recovery. Finally, amalgamating the 4 key types and sources of advice to examine the impact of combinations of these types and sources of advice also improved the strength of the relationship. Implications The findings will assist in the understanding of young firms in general and growth more specifically, particularly the role and importance of specific sources, types and combinations of business support used more extensively by new young growth-oriented firms. Value This research may assist in processes designed to allow entrepreneurs to make better decisions; educators and support organizations to develop better advice and assistance, and Governments design better conditions for the creation of new growth-oriented businesses.
Resumo:
The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages <1, 1-5 and >5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight <-1 was 57%, >-1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 ± 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long-term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth.
Resumo:
The availability of innumerable intelligent building (IB) products, and the current dearth of inclusive building component selection methods suggest that decision makers might be confronted with the quandary of forming a particular combination of components to suit the needs of a specific IB project. Despite this problem, few empirical studies have so far been undertaken to analyse the selection of the IB systems, and to identify key selection criteria for major IB systems. This study is designed to fill these research gaps. Two surveys: a general survey and the analytic hierarchy process (AHP) survey are proposed to achieve these objectives. The first general survey aims to collect general views from IB experts and practitioners to identify the perceived critical selection criteria, while the AHP survey was conducted to prioritize and assign the important weightings for the perceived criteria in the general survey. Results generally suggest that each IB system was determined by a disparate set of selection criteria with different weightings. ‘Work efficiency’ is perceived to be most important core selection criterion for various IB systems, while ‘user comfort’, ‘safety’ and ‘cost effectiveness’ are also considered to be significant. Two sub-criteria, ‘reliability’ and ‘operating and maintenance costs’, are regarded as prime factors to be considered in selecting IB systems. The current study contributes to the industry and IB research in at least two aspects. First, it widens the understanding of the selection criteria, as well as their degree of importance, of the IB systems. It also adopts a multi-criteria AHP approach which is a new method to analyse and select the building systems in IB. Further research would investigate the inter-relationship amongst the selection criteria.
Resumo:
This report fully summarises a project designed to enhance commercial real estate performance within both operational and investment contexts through the development of a model aimed at supporting improved decision-making. The model is based on a risk adjusted discounted cash flow, providing a valuable toolkit for building managers, owners, and potential investors for evaluating individual building performance in terms of financial, social and environmental criteria over the complete life-cycle of the asset. The ‘triple bottom line’ approach to the evaluation of commercial property has much significance for the administrators of public property portfolios in particular. It also has applications more generally for the wider real estate industry given that the advent of ‘green’ construction requires new methods for evaluating both new and existing building stocks. The research is unique in that it focuses on the accuracy of the input variables required for the model. These key variables were largely determined by market-based research and an extensive literature review, and have been fine-tuned with extensive testing. In essence, the project has considered probability-based risk analysis techniques that required market-based assessment. The projections listed in the partner engineers’ building audit reports of the four case study buildings were fed into the property evaluation model developed by the research team. The results are strongly consistent with previously existing, less robust evaluation techniques. And importantly, this model pioneers an approach for taking full account of the triple bottom line, establishing a benchmark for related research to follow. The project’s industry partners expressed a high degree of satisfaction with the project outcomes at a recent demonstration seminar. The project in its existing form has not been geared towards commercial applications but it is anticipated that QDPW and other industry partners will benefit greatly by using this tool for the performance evaluation of property assets. The project met the objectives of the original proposal as well as all the specified milestones. The project has been completed within budget and on time. This research project has achieved the objective by establishing research foci on the model structure, the key input variable identification, the drivers of the relevant property markets, the determinants of the key variables (Research Engine no.1), the examination of risk measurement, the incorporation of risk simulation exercises (Research Engine no.2), the importance of both environmental and social factors and, finally the impact of the triple bottom line measures on the asset (Research Engine no. 3).
Resumo:
Principal Topic : According to Shane & Venkataraman (2000) entrepreneurship consists of the recognition and exploitation of venture ideas - or opportunities as they often called - to create future goods and services. This definition puts venture ideas is at the heart of entrepreneurship research. Substantial research has been done on venture ideas in order to enhance our understanding of this phenomenon (e.g. Choi & Shepherd, 2004; Shane, 2000; Shepherd & DeTienne, 2005). However, we are yet to learn what factors drive entrepreneurs' perceptions of the relative attractiveness of venture ideas, and how important different idea characteristics are for such assessments. Ruef (2002) recognized that there is an uneven distribution of venture ideas undertaken by entrepreneurs in the USA. A majority introduce either a new product/service or access a new market or market segment. A smaller percentage of entrepreneurs introduce a new method of production, organizing, or distribution. This implies that some forms of venture ideas are perceived by entrepreneurs as more important or valuable than others. However, Ruef does not provide any information regarding why some forms of venture ideas are more common than others among entrepreneurs. Therefore, this study empirically investigates what factors affect the attractiveness of venture ideas as well as their relative importance. Based on two key characteristics of venture ideas, namely venture idea newness and relatedness, our study investigates how different types and degrees of newness and relatedness of venture ideas affect their attractiveness as perceived by expert entrepreneurs. Methodology/Key : Propositions According to Schumpeter (1934) entrepreneurs introduce different types of venture ideas such as new products/services, new method of production, enter into new markets/customer and new method of promotion. Further, according to Schumpeter (1934) and Kirzner (1973) venture ideas introduced to the market range along a continuum of innovative to imitative ideas. The distinction between these two extremes of venture idea highlights an important property of venture idea, namely their newness. Entrepreneurs, in order to gain competitive advantage or above average returns introduce their venture ideas which may be either new to the world, new to the market that they seek to enter, substantially improved from current offerings and an imitative form of existing offerings. Expert entrepreneurs may be more attracted to venture ideas that exhibit high degree of newness because of the higher newness is coupled with increased market potential (Drucker, 1985) Moreover, certain individual characteristics also affect the attractiveness of venture idea. According to Shane (2000), individual's prior knowledge is closely associated with the recognition of venture ideas. Sarasvathy's (2001) Effectuation theory proposes a high degree of relatedness between venture ideas and the resource position of the individual. Thus, entrepreneurs may be more attracted to venture ideas that are closely aligned with the knowledge and/or resources they already possess. On the other hand, the potential financial gain (Shepherd & DeTienne, 2005) may be larger for ideas that are not close to the entrepreneurs' home turf. Therefore, potential financial gain is a stimulus that has to be considered separately. We aim to examine how entrepreneurs weigh considerations of different forms of newness and relatedness as well as potential financial gain in assessing the attractiveness of venture ideas. We use conjoint analysis to determine how expert entrepreneurs develop preferences for venture ideas which involved with different degrees of newness, relatedness and potential gain. This analytical method paves way to measure the trade-offs they make when choosing a particular venture idea. The conjoint analysis estimates respondents' preferences in terms of utilities (or part-worth) for each level of newness, relatedness and potential gain of venture ideas. A sample of 50 expert entrepreneurs who were awarded young entrepreneurship awards in Sri Lanka in 2007 is used for interviews. Each respondent is interviewed providing with 32 scenarios which explicate different combinations of possible profiles open them into consideration. Conjoint software (SPSS) is used to analyse data. Results and Implications : The data collection of this study is still underway. However, results of this study will provide information regarding the attractiveness of each level of newness, relatedness and potential gain of venture idea and their relative importance in a business model. Additionally, these results provide important implications for entrepreneurs, consultants and other stakeholders as regards the importance of different of attributes of venture idea coupled with different levels. Entrepreneurs, consultants and other stakeholders could make decisions accordingly.
Resumo:
Summary There are four interactions to consider between energy intake (EI) and energy expenditure (EE) in the development and treatment of obesity. (1) Does sedentariness alter levels of EI or subsequent EE? and (2) Do high levels of EI alter physical activity or exercise? (3) Do exercise-induced increases in EE drive EI upwards and undermine dietary approaches to weight management and (4) Do low levels of EI elevate or decrease EE? There is little evidence that sedentariness alters levels of EI. This lack of cross-talk between altered EE and EI appears to promote a positive EB. Lifestyle studies also suggest that a sedentary routine actually offers the opportunity for over-consumption. Substantive changes in non exercise activity thermogenesis are feasible, but not clearly demonstrated. Cross talk between elevated EE and EI is initially too weak and takes too long to activate, to seriously threaten dietary approaches to weight management. It appears that substantial fat loss is possible before intake begins to track a sustained elevation of EE. There is more evidence that low levels of EI does lower physical activity levels, in relatively lean men under conditions of acute or prolonged semi-starvation and in dieting obese subjects. During altered EB there are a number of small but significant changes in the components of EE, including (i) sleeping and basal metabolic rate, (ii) energy cost of weight change alters as weight is gained or lost, (iii) exercise efficiency, (iv) energy cost of weight bearing activities, (v) during substantive overfeeding diet composition (fat versus carbohydrate) will influence the energy cost of nutrient storage by ~ 15%. The responses (i-v) above are all “obligatory” responses. Altered EB can also stimulate facultative behavioural responses, as a consequence of cross-talk between EI and EE. Altered EB will lead to changes in the mode duration and intensity of physical activities. Feeding behaviour can also change. The degree of inter-individual variability in these responses will define the scope within which various mechanisms of EB compensation can operate. The relative importance of “obligatory” versus facultative, behavioural responses -as components of EB control- need to be defined.
Resumo:
The studies in the thesis were derived from a program of research focused on centre-based child care in Australia. The studies constituted an ecological analysis as they examined proximal and distal factors which have the potential to affect children's developmental opportunities (Bronfenbrenner, 1979). The project was conducted in thirty-two child care centres located in south-east Queensland. Participants in the research included staff members at the centres, families using the centres and their children. The first study described the personal and professional characteristics of one hundred and forty-four child care workers, as well as their job satisfaction and job commitment. Factors impinging on the stability of care afforded to children were examined, specifically child care workers' intentions to leave their current position and actual staff turnover at a twelve month follow-up. This is an ecosystem analysis (Bronfenbrenner & Crouter, 1983), as it examined the world of work for carers; a setting not directly involving the developing child, but which has implications for children's experiences. Staff job satisfaction was focused on working with children and other adults, including parents and colleagues. Involvement with children was reported as being the most rewarding aspect of the work. This intrinsic satisfaction was enough to sustain caregivers' efforts to maintain their employment in child care programs. It was found that, while improving working conditions may help to reduce turnover, it is likely that moderate turnover rates will remain as child care staff work in relatively small centres and they leave in order to improve career prospects. Departure from a child care job appeared to be as much about improving career opportunities or changing personal circumstances, as it was about poor wages and working conditions. In the second study, factors that influence maternal satisfaction with child care arrangements were examined. The focus included examination of the nature and qualities of parental interaction with staff. This was a mesosystem analysis (Bronfenbrenner & Crouter, 1983), as it considered the links between family and child care settings. Two hundred and twenty-two questionnaires were returned from mothers whose children were enrolled in the participating centres. It was found that maternal satisfaction with child care encompassed the domains of child-centred and parent-centred satisfaction. The nature and range of responses in the quantitative and qualitative data indicated that these parents were genuinely satisfied with their children's care. In the prediction of maternal satisfaction with child care, single parents, mothers with high role satisfaction, and mothers who were satisfied with the frequency of staff contact and degree of supportive communication had higher levels of satisfaction with their child care arrangements. The third study described the structural and process variations within child care programs and examined program differences for compliance with regulations and differences by profit status of the centre, as a microsystem analysis (Bronfenbrenner, 1979). Observations were made in eighty-three programs which served children from two to five years. The results of the study affirmed beliefs that nonprofit centres are superior in the quality of care provided, although this was not to a level which meant that the care in for-profit centres was inadequate. Regulation of structural features of child care programs, per se, did not guarantee higher quality child care as measured by global or process indicators. The final study represented an integration of a range of influences in child care and family settings which may impact on development. Features of child care programs which predict children's social and cognitive development, while taking into account child and family characteristics, were identified. Results were consistent with other research findings which show that child and family characteristics and child care quality predict children's development. Child care quality was more important to the prediction of social development, while family factors appeared to be more predictive of cognitive/language development. An influential variable predictive of development was the period of time which the child had been in the centre. This highlighted the importance of the stability of child care arrangements. Child care quality features which had most influence were global ratings of the qualities of the program environment. However, results need to be interpreted cautiously as the explained variance in the predictive models developed was low. The results of these studies are discussed in terms of the implications for practice and future research. Considerations for an expanded view of ecological approaches to child care research are outlined. Issues discussed include the need to generate child care research which is relevant to social policy development, the implications of market driven policies for child care services, professionalism and professionalisation of child care work, and the need to reconceptualise child care research when the goal is to develop greater theoretical understanding about child care environments and developmental processes.
Resumo:
A degree of judicial caution in accepting the assertion of a plaintiff as to what he or she would have done, if fully informed of risks, is clearly evident upon a review of decisions applying the common law. Civil liability legislation in some jurisdictions now precludes assertion evidence by a plaintiff. Although this legislative change was seen as creating a significant challenge for plaintiffs seeking to discharge the onus of proof of establishing causation in such cases, recent decisions suggest a more limited practical effect. While a plaintiff’s ex post facto assertions as to what he or she would have done if fully informed of risks may now be inadmissible, objective and subjective evidence as to the surrounding facts and circumstances, in particular the plaintiff’s prior attitudes and conduct, and the assertion evidence of others remains admissible. Given the court’s reliance on both objective and subjective evidence, statistical evidence may be of increasing importance.
Resumo:
Principal Topic Venture ideas are at the heart of entrepreneurship (Davidsson, 2004). However, we are yet to learn what factors drive entrepreneurs’ perceptions of the attractiveness of venture ideas, and what the relative importance of these factors are for their decision to pursue an idea. The expected financial gain is one factor that will obviously influence the perceived attractiveness of a venture idea (Shepherd & DeTienne, 2005). In addition, the degree of novelty of venture ideas along one or more dimensions such as new products/services, new method of production, enter into new markets/customer and new method of promotion may affect their attractiveness (Schumpeter, 1934). Further, according to the notion of an individual-opportunity nexus venture ideas are closely associated with certain individual characteristics (relatedness). Shane (2000) empirically identified that individual’s prior knowledge is closely associated with the recognition of venture ideas. Sarasvathy’s (2001; 2008) Effectuation theory proposes a high degree of relatedness between venture ideas and the resource position of the individual. This study examines how entrepreneurs weigh considerations of different forms of novelty and relatedness as well as potential financial gain in assessing the attractiveness of venture ideas. Method I use conjoint analysis to determine how expert entrepreneurs develop preferences for venture ideas which involved with different degrees of novelty, relatedness and potential gain. The conjoint analysis estimates respondents’ preferences in terms of utilities (or part-worth) for each level of novelty, relatedness and potential gain of venture ideas. A sample of 32 expert entrepreneurs who were awarded young entrepreneurship awards were selected for the study. Each respondent was interviewed providing with 32 scenarios which explicate different combinations of possible profiles open them into consideration. Results and Implications Results indicate that while the respondents do not prefer mere imitation they receive higher utility for low to medium degree of newness suggesting that high degrees of newness are fraught with greater risk and/or greater resource needs. Respondents pay considerable weight on alignment with the knowledge and skills they already posses in choosing particular venture idea. The initial resource position of entrepreneurs is not equally important. Even though expected potential financial gain gives substantial utility, result indicate that it is not a dominant factor for the attractiveness of venture idea.
Resumo:
One of the main causes of above knee or transfemoral amputation (TFA) in the developed world is trauma to the limb. The number of people undergoing TFA due to limb trauma, particularly due to war injuries, has been increasing. Typically the trauma amputee population, including war-related amputees, are otherwise healthy, active and desire to return to employment and their usual lifestyle. Consequently there is a growing need to restore long-term mobility and limb function to this population. Traditionally transfemoral amputees are provided with an artificial or prosthetic leg that consists of a fabricated socket, knee joint mechanism and a prosthetic foot. Amputees have reported several problems related to the socket of their prosthetic limb. These include pain in the residual limb, poor socket fit, discomfort and poor mobility. Removing the socket from the prosthetic limb could eliminate or reduce these problems. A solution to this is the direct attachment of the prosthesis to the residual bone (femur) inside the residual limb. This technique has been used on a small population of transfemoral amputees since 1990. A threaded titanium implant is screwed in to the shaft of the femur and a second component connects between the implant and the prosthesis. A period of time is required to allow the implant to become fully attached to the bone, called osseointegration (OI), and be able to withstand applied load; then the prosthesis can be attached. The advantages of transfemoral osseointegration (TFOI) over conventional prosthetic sockets include better hip mobility, sitting comfort and prosthetic retention and fewer skin problems on the residual limb. However, due to the length of time required for OI to progress and to complete the rehabilitation exercises, it can take up to twelve months after implant insertion for an amputee to be able to load bear and to walk unaided. The long rehabilitation time is a significant disadvantage of TFOI and may be impeding the wider adoption of the technique. There is a need for a non-invasive method of assessing the degree of osseointegration between the bone and the implant. If such a method was capable of determining the progression of TFOI and assessing when the implant was able to withstand physiological load it could reduce the overall rehabilitation time. Vibration analysis has been suggested as a potential technique: it is a non destructive method of assessing the dynamic properties of a structure. Changes in the physical properties of a structure can be identified from changes in its dynamic properties. Consequently vibration analysis, both experimental and computational, has been used to assess bone fracture healing, prosthetic hip loosening and dental implant OI with varying degrees of success. More recently experimental vibration analysis has been used in TFOI. However further work is needed to assess the potential of the technique and fully characterise the femur-implant system. The overall aim of this study was to develop physical and computational models of the TFOI femur-implant system and use these models to investigate the feasibility of vibration analysis to detect the process of OI. Femur-implant physical models were developed and manufactured using synthetic materials to represent four key stages of OI development (identified from a physiological model), simulated using different interface conditions between the implant and femur. Experimental vibration analysis (modal analysis) was then conducted using the physical models. The femur-implant models, representing stage one to stage four of OI development, were excited and the modal parameters obtained over the range 0-5kHz. The results indicated the technique had limited capability in distinguishing between different interface conditions. The fundamental bending mode did not alter with interfacial changes. However higher modes were able to track chronological changes in interface condition by the change in natural frequency, although no one modal parameter could uniquely distinguish between each interface condition. The importance of the model boundary condition (how the model is constrained) was the key finding; variations in the boundary condition altered the modal parameters obtained. Therefore the boundary conditions need to be held constant between tests in order for the detected modal parameter changes to be attributed to interface condition changes. A three dimensional Finite Element (FE) model of the femur-implant model was then developed and used to explore the sensitivity of the modal parameters to more subtle interfacial and boundary condition changes. The FE model was created using the synthetic femur geometry and an approximation of the implant geometry. The natural frequencies of the FE model were found to match the experimental frequencies within 20% and the FE and experimental mode shapes were similar. Therefore the FE model was shown to successfully capture the dynamic response of the physical system. As was found with the experimental modal analysis, the fundamental bending mode of the FE model did not alter due to changes in interface elastic modulus. Axial and torsional modes were identified by the FE model that were not detected experimentally; the torsional mode exhibited the largest frequency change due to interfacial changes (103% between the lower and upper limits of the interface modulus range). Therefore the FE model provided additional information on the dynamic response of the system and was complementary to the experimental model. The small changes in natural frequency over a large range of interface region elastic moduli indicated the method may only be able to distinguish between early and late OI progression. The boundary conditions applied to the FE model influenced the modal parameters to a far greater extent than the interface condition variations. Therefore the FE model, as well as the experimental modal analysis, indicated that the boundary conditions need to be held constant between tests in order for the detected changes in modal parameters to be attributed to interface condition changes alone. The results of this study suggest that in a clinical setting it is unlikely that the in vivo boundary conditions of the amputated femur could be adequately controlled or replicated over time and consequently it is unlikely that any longitudinal change in frequency detected by the modal analysis technique could be attributed exclusively to changes at the femur-implant interface. Therefore further development of the modal analysis technique would require significant consideration of the clinical boundary conditions and investigation of modes other than the bending modes.
Resumo:
The importance of the first year experience (FYE) to success at university is well documented and supported with the transition into university regarded as crucial. While there is also support for the notion that a successful FYE should have a whole-of-institution focus and models have been proposed, many institutions still face challenges in achieving institution-wide FYE program implementation. This paper discusses the origins, theoretical and empirical bases and structure of an institution-wide approach to the FYE. It uses a case study of the Transitions In Project (TIP) at the Queensland University of Technology to illustrate how institution-wide FYE program implementation can be achieved and sustained. TIP had four inter-related projects focussing on at-risk students, first year curriculum, learning resources and staff development. The key aim of TIP was to identify good practice and institutionalise it in a sustainable way. The degree of success in achieving this is evaluated.
Resumo:
This paper presents the results of a pilot study examining the factors that impact most on the effective implementation of, and improvement to, Quality Mangement Sytems (QMSs) amongst Indonesian construction companies. Nine critical factors were identified from an extensive literature review, and a survey was conducted of 23 respondents from three specific groups (Quality Managers, Project Managers, and Site Engineers) undertaking work in the Indonesian infrastructure construction sector. The data has been analyzed initially using simple descriptive techniques. This study reveals that different groups within the sector have different opinions of the factors regardless of the degree of importance of each factor. However, the evaluation of construction project success and the incentive schemes for high performance staff, are the two factors that were considered very important by most of the respondents in all three groups. In terms of their assessment of tools for measuring contractor’s performance, additional QMS guidelines, techniques related to QMS practice provided by the Government, and benchmarking, a clear majority in each group regarded their usefulness as ‘of some importance’.
Resumo:
The concept of non-destructive testing (NDT) of materials and structures is of immense importance in engineering and medicine. Several NDT methods including electromagnetic (EM)-based e.g. X-ray and Infrared; ultrasound; and S-waves have been proposed for medical applications. This paper evaluates the viability of near infrared (NIR) spectroscopy, an EM method for rapid non-destructive evaluation of articular cartilage. Specifically, we tested the hypothesis that there is a correlation between the NIR spectrum and the physical and mechanical characteristics of articular cartilage such as thickness, stress and stiffness. Intact, visually normal cartilage-on-bone plugs from 2-3yr old bovine patellae were exposed to NIR light from a diffuse reflectance fibre-optic probe and tested mechanically to obtain their thickness, stress, and stiffness. Multivariate statistical analysis-based predictive models relating articular cartilage NIR spectra to these characterising parameters were developed. Our results show that there is a varying degree of correlation between the different parameters and the NIR spectra of the samples with R2 varying between 65 and 93%. We therefore conclude that NIR can be used to determine, nondestructively, the physical and functional characteristics of articular cartilage.
Resumo:
A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.
Resumo:
The study of venture idea characteristics and the contextual fit between venture ideas and individuals are key research goals in entrepreneurship (Davidsson, 2004). However, to date there has been limited scholarly attention given to these phenomena. Accordingly, this study aims to help fill the gap by investigating the importance of novelty and relatedness of venture ideas in entrepreneurial firms. On the premise that new venture creation is a process and that research should be focused on the early stages of the venturing process, this study primarily focuses its attention on examining how venture idea novelty and relatedness affect the performance in the venture creation process. Different types and degrees of novelty are considered here. Relatedness is shown to be based on individuals’ prior knowledge and resource endowment. Performance in the venture creation process is evaluated according to four possible outcomes: making progress, getting operational, being terminated and achieving positive cash flow. A theoretical model is developed demonstrating the relationship between these variables along with the investment of time and money. Several hypotheses are developed to be tested. Among them, it is hypothesised that novelty hinders short term performance in the venture creation process. On the other hand knowledge and resource relatedness are hypothesised to promote performance. An experimental study was required in order to understand how different types and degrees of novelty and relatedness of venture ideas affect the attractiveness of venture ideas in the eyes of experienced entrepreneurs. Thus, the empirical work in this thesis was based on two separate studies. In the first one, a conjoint analysis experiment was conducted on 32 experienced entrepreneurs in order to ascertain attitudinal preferences regarding venture idea attractiveness based on novelty, relatedness and potential financial gains. This helped to estimate utility values for different levels of different attributes of venture ideas and their relative importance in the attractiveness. The second study was a longitudinal investigation of how venture idea novelty and relatedness affect the performance in the venture creation process. The data for this study is from the Comprehensive Australian Study for Entrepreneurial Emergence (CAUSEE) project that has been established in order to explore the new venture creation process in Australia. CAUSEE collects data from a representative sample of over 30,000 households in Australia using random digit dialling (RDD) telephone interviews. From these cases, data was collected at two points in time during a 12 month period from 493 firms, who are currently involved in the start-up process. Hypotheses were tested and inferences were derived through descriptive statistics, confirmatory factor analysis and structural equation modelling. Results of study 1 indicate that venture idea characteristics have a role in the attractiveness and entrepreneurs prefer to introduce a moderate degree of novelty across all types of venture ideas concerned. Knowledge relatedness is demonstrated to be a more significant factor in attractiveness than resource relatedness. Results of study 2 show that the novelty hinders nascent venture performance. On the other hand, resource relatedness has a positive impact on performance unlike knowledge relatedness which has none. The results of these studies have important implications for potential entrepreneurs, investors, researchers, consultants etc. by developing a better understanding in the venture creation process and its success factors in terms of both theory and practice.