905 resultados para stable crack growth


Relevância:

20.00% 20.00%

Publicador:

Resumo:

This study contributes to the literature on international retailing by addressing a gap in the literature as to how retailers from emerging markets expand internationally. This historical case study analyzes the growth and internationalization process of Chilean retailer Falabella, one of the largest in Latin America and has been able to compete with multinationals from developed countries. The research is based upon primary and secondary data sources including 33 oral interviews with company managers and family executives, as well as industry data, corporate reports, and trade journals. Drawing on institutional theory, the findings show that by belonging to a family conglomerate, engaging in networks and partnerships, organizational learning, and having an experienced management team helped Falabella gain legitimacy in all international markets.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Fibroblasts and their activated phenotype, myofibroblasts, are the primary cell types involved in the contraction associated with dermal wound healing. Recent experimental evidence indicates that the transformation from fibroblasts to myofibroblasts involves two distinct processes: the cells are stimulated to change phenotype by the combined actions of transforming growth factor β (TGFβ) and mechanical tension. This observation indicates a need for a detailed exploration of the effect of the strong interactions between the mechanical changes and growth factors in dermal wound healing. We review the experimental findings in detail and develop a model of dermal wound healing that incorporates these phenomena. Our model includes the interactions between TGFβ and collagenase, providing a more biologically realistic form for the growth factor kinetics than those included in previous mechanochemical descriptions. A comparison is made between the model predictions and experimental data on human dermal wound healing and all the essential features are well matched.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Sericin and fibroin are the two major proteins in the silk fibre produced by the domesticated silkworm, Bombyx mori. Fibroin has been extensively investigated as a biomaterial. We have previously shown that fibroin can function successfully as a substratum for growing cells of the eye. Sericin has been so far neglected as a biomaterial because of suspected allergenic activity. However, this misconception has now been dispelled, and sericin’s biocompatibility is currently indisputable. Aiming at promoting sericin as a possible substratum for the growth of corneal cells in order to make tissue-engineered constructs for the restoration of the ocular surface, in this study we investigated the attachment and growth in vitro of human corneal limbal epithelial cells (HLECs) on sericin-based membranes. Sericin was isolated and regenerated from the silkworm cocoons by an aqueous procedure, manufactured into membranes, and characterized (mechanical properties, structural analysis, contact angles). Primary cell cultures from two donors were established in serum-supplemented media in the presence of murine feeder cells. Membranes made of sericin and fibroin-sericin blends were assessed in vitro as substrata for HLECs in a serum-free medium, in a cell attachment assay and in a 3-day cell growth experiment. While the mechanical characteristics of sericin were found to be inferior to those of fibroin, its ability to enhance the attachment of HLECs was significantly superior to fibroin, as revealed by the PicoGreen® assay. Evidence was also obtained that cells can grow and differentiate on these substrata.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Although Design Led Innovation activities aim to raise the value of design within the business, knowledge about which tools are available to support companies and how to apply them to make the connection between design for new product development and design as a strategic driver of growth is needed. This paper presents a conceptual method to supplement existing process and tools to assist companies to grow through design. The model extends the authors’ previous work to explore how through storytelling, customer observation can be captured and translated into new meaning, then creating new design propositions shaped into product needs, which can drive internal business activities, brand and the strategic vision. The paper contributes to a gap in the theoretical frameworks and literature by highlighting the need to align and scale design processes which match the needs of SME’s as they transition along a trajectory to become design led businesses.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

This paper reports on a study that focused on growth of understanding about teaching geometry by a group of prospective teachers engaged in lesson plan study within a computer-supported collaborative learning (CSCL) environment. Participation in the activity was found to facilitate considerable growth in the participants’ pedagogical-content knowledge (PCK). Factors that influenced growth in PCK included the nature of the lesson planning task, the cognitive scaffolds inserted into the CSCL virtual space, the meta-language scaffolds provided to the participants, and the provision of both private and public discourse spaces. The paper concludes with recommendations for enhancing effective knowledge-building discourse about mathematics PCK within prospective teacher education CSCL environments.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

This chapter argues that evolutionary economics should be founded upon complex systems theory rather than neo-Darwinian analogies concerning natural selection, which focus on supply side considerations and competition amongst firms and technologies. It suggests that conceptions such as production and consumption functions should be replaced by network representations, in which the preferences or, more correctly, the aspirations of consumers are fundamental and, as such, the primary drivers of economic growth. Technological innovation is viewed as a process that is intermediate between these aspirational networks, and the organizational networks in which goods and services are produced. Consumer knowledge becomes at least as important as producer knowledge in determining how economic value is generated. It becomes clear that the stability afforded by connective systems of rules is essential for economic flexibility to exist, but that too many rules result in inert and structurally unstable states. In contrast, too few rules result in a more stable state, but at a low level of ordered complexity. Economic evolution from this perspective is explored using random and scale free network representations of complex systems.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Teacher professional development provided by education advisors as one-off, centrally offered sessions does not always result in change in teacher knowledge, beliefs, attitudes or practice in the classroom. As the mathematics education advisor in this study, I set out to investigate a particular method of professional development so as to influence change in a practising classroom teacher’s knowledge and practices. The particular method of professional development utilised in this study was based on several principles of effective teacher professional development and saw me working regularly in a classroom with the classroom teacher as well as providing ongoing support for her for a full school year. The intention was to document the effects of this particular method of professional development in terms of the classroom teacher’s and my professional growth to provide insights for others working as education advisors. The professional development for the classroom teacher consisted of two components. The first was the co-operative development and implementation of a mental computation instructional program for the Year 3 class. The second component was the provision of ongoing support for the classroom teacher by the education advisor. The design of the professional development and the mental computation instructional program were progressively refined throughout the year. The education advisor fulfilled multiple roles in the study as teacher in the classroom, teacher educator working with the classroom teacher and researcher. Examples of the professional growth of the classroom teacher and the education advisor which occurred as sequences of changes (growth networks, Hollingsworth, 1999) in the domains of the professional world of the classroom teacher and education advisor were drawn from the large body of data collected through regular face-to-face and email communications between the classroom teacher and the education advisor as well as from transcripts of a structured interview. The Interconnected Model of Professional Growth (Clarke & Hollingsworth, 2002; Hollingsworth, 1999) was used to summarise and represent each example of the classroom teacher’s professional growth. A modified version of this model was used to summarise and represent the professional growth of the education advisor. This study confirmed that the method of professional development utilised could lead to significant teacher professional growth related directly to her work in the classroom. Using the Interconnected Model of Professional Growth to summarise and represent the classroom teacher’s professional growth and the modified version for my professional growth assisted with the recognition of examples of how we both changed. This model has potential to be used more widely by education advisors when preparing, implementing, evaluating and following-up on planned teacher professional development activities. The mental computation instructional program developed and trialled in the study was shown to be a successful way of sequencing and managing the teaching of mental computation strategies and related number sense understandings to Year 3 students. This study was conducted in one classroom, with one teacher in one school. The strength of this study was the depth of teacher support provided made possible by the particular method of the professional development, and the depth of analysis of the process. In another school, or with another teacher, this might not have been as successful. While I set out to change my practice as an education advisor I did not expect the depth of learning I experienced in terms of my knowledge, beliefs, attitudes and practices as an educator of teachers. This study has changed the way in which I plan to work as an education advisor in the future.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

It is to estimate the trend of suicide rate changes during the past three decades in China and try to identify its social and economic correlates. Official data of suicide rates and economic indexes during 1982–2005 from Shandong Province of China were analyzed. The suicide data were categorized for the rural / urban location and gender, and the economic indexes include GDP, GDP per capita, rural income, and urban income, all adjusted for inflation. We found a significant increase of economic development and decrease of suicide rates over the past decades under study. The suicide rate decrease is correlated with the tremendous growth of economy. The unusual decrease of Chinese suicide rates in the past decades is accounted for within the Chinese cultural contexts and maybe by the Strain Theory of Suicide.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

It is generally accepted that there is a close relationship between property investment and construction activity. The construction sector plays a crucial role in economic development, especially for a developing nation such as Malaysia. However, the volume of new properties added to the property market is only a fraction of the total volume of the property market. Is the conventional assumption of the relationship between property investment and construction supported by empirical data? This paper revisits the tripartite relationships between economic growths, property investment and construction activities with official Malaysian 2000Q1-2010Q4 quarterly time series data. The Granger causality tests are used to establish the causality runs from the GDP to the value of property transactions, and the growth of construction activities to GDP growth. The result is expected to be useful for policymakers and industrial practitioners in formulating industrial policies and corporate strategies.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Transport and logistics are essential to effective business. Very little is currently known about the impact of improved transport on micro-enterprises in developing economies and whether improvements in this area would assist the very poor. This paper looks at the obstacles of an inefficient transport facilitation system and the high costs incurred by 22 survival micro-entrepreneurs funded by the same local NGO and operating in diverse industry sectors in a peri-urban context in Mozambique. Six case studies are selected to illustrate the most common constraints they face. The perspectives of the micro-business owners are confronted with those of government officials and community leaders for two reasons: to identify any mismatch and to discuss possible solutions. Significant discrepancies are detected between government agenda and needs of the population, while community-based entrepreneurship (CBE) is discussed as a possible collective strategy in dealing with the problem.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

This thesis is about the Australian domain name system and, in particular, the principles governing the registration of domain names in the '.au' country code domain space. It examines the different types of registration systems adopted in country code domain spaces and categorises them according to the extent to which they impose restrictions on registration, ranging from restrictive to unrestrictive. A comparative analysis is made of the restrictive registration system in Australia and the United Kingdom‘s unrestrictive system.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Immigrant entrepreneurship, or, self-employment by immigrants (Light & Bonacich, 1988), has been of growing interest to researchers (Hosler, 1996). This is due in part to major immigrant receiving countries, such as Australia, the United States, Canada, the United Kingdom and Western Europe, experiencing a high growth rate in their immigrant populations, leading to a more visible presence of immigrant business in major cities (Woon, 2008). By starting their own businesses, immigrant entrepreneurs may circumvent some of the barriers and disadvantages encountered in looking for a job (Sequeira & Rasheed, 2006). Successful immigrant entrepreneurs will integrate into the economy by creating jobs, providing products and services for members of their own ethnic community and society, as well as introducing new products and services that expand consumers’ choices (Rath & Kloosterman, 2000). Immigrant entrepreneurs tend to start business within their ethnic enclave, as it is an integral part of their social and cultural context and the location where ethnic resources reside (Logan et al., 2002). An ethnic enclave is an interdependent network of social and business relationships that are geographically concentrated with its co-ethnic people (Portes & Bach, 1985).

Relevância:

20.00% 20.00%

Publicador:

Resumo:

As civil infrastructures such as bridges age, there is a concern for safety and a need for cost-effective and reliable monitoring tool. Different diagnostic techniques are available nowadays for structural health monitoring (SHM) of bridges. Acoustic emission is one such technique with potential of predicting failure. The phenomenon of rapid release of energy within a material by crack initiation or growth in form of stress waves is known as acoustic emission (AE). AEtechnique involves recording the stress waves bymeans of sensors and subsequent analysis of the recorded signals,which then convey information about the nature of the source. AE can be used as a local SHM technique to monitor specific regions with visible presence of cracks or crack prone areas such as welded regions and joints with bolted connection or as a global technique to monitor the whole structure. Strength of AE technique lies in its ability to detect active crack activity, thus helping in prioritising maintenance work by helping focus on active cracks rather than dormant cracks. In spite of being a promising tool, some challenges do still exist behind the successful application of AE technique. One is the generation of large amount of data during the testing; hence an effective data analysis and management is necessary, especially for long term monitoring uses. Complications also arise as a number of spurious sources can giveAEsignals, therefore, different source discrimination strategies are necessary to identify genuine signals from spurious ones. Another major challenge is the quantification of damage level by appropriate analysis of data. Intensity analysis using severity and historic indices as well as b-value analysis are some important methods and will be discussed and applied for analysis of laboratory experimental data in this paper.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The Western Downs region, located in Southern Queensland, about 200 kilometres west of Brisbane, has been experiencing rapid and significant changes over the past years, due to a massive boom in the energy sector. The rapid growth triggered by the development of mining and energy sectors has generated environmental, socio-economic and land use issues, and has revealed strong weaknesses within the region’s current governance arrangements. The present paper develops a four-stage approach to managing current and expected changes in a resource-based region under tremendous stress and uncertainty.