986 resultados para pharmaceutical innovation


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This study investigates the links between product innovation and external collaboration and between future product innovation and past abandonment in small and medium sized firms. Our findings from 449 manufacturing firms indicated firms that sought ideas or solutions from an external network such as suppliers, or business partners reported higher levels of new product introduction than firms without any external collaboration. Further, firms with past abandonment experiences reported higher levels of new product introduction than firms without such experience. Additionally, the findings indicated that firms with external collaboration were more likely to introduce new products even if they had previously experienced abandonment of a product innovation than firms without external collaboration. Implications, limitations and future research are outlined.

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Introduction. There are two binding sites on the β1-adrenoceptor (AR), β1H and β1L corresponding to high and low affinity binding sites respectively, which can be activated to cause cardiostimulation. Some β-blockers that block β1AR and β2ARs can activate β1LARs at higher concentrations than those required to cause blockade. The β2AR does not form a corresponding low affinity binding site and therefore we postulated that heterologous amino acids are responsible for the formation of β1LAR. Aim. To investigate whether heterologous amino acids of transmembrane domain V (TMDV) of β1AR and β2ARs contribute to β1LAR. Methods. β1ARs, β2ARs and mutant β1ARs containing all (β1(β2TMDV)AR) or single amino acids of TMDV of the β2AR were prepared and stably expressed in Chinese Hamster Ovary cells. Concentration-effect curves for cyclicAMP accumulation were carried out for (-)-CGP12177 in the absence or presence of (-)-bupranolol. Results. The potencies (pEC50) of (-)-CGP12177 were β2AR (9.24 ± 0.14, n = 5), β1(V230I)AR (9.07 ± 0.07, n = 10), β1(β2TMDV)AR (8.86 ± 0.10, n = 15), β1(R222Q)AR (8.09 ± 0.29, n = 6), β1AR (8.00 ± 0.11, n = 11). The affinities (pKB) of (-)-bupranolol were β2AR (9.82 ± 0.52, n = 5), β1(V230I)AR (7.64 ± 0.12, n = 8), β1(β2TMV)AR (8.06 ± 0.17, n = 8), β1(R222Q)AR (7.33 ± 0.23, n = 5), β1AR (7.23 ± 0.23, n = 5). Discussion. The potency of (-)-CGP12177 was higher at β2AR than at β1AR consistent with activation through a low affinity site at the β1AR (β1LAR). The presence of V230 in β1AR accounted for the lower potency of (-)-CGP 12177. The affinity of (-)-bupranolol was lower at β1AR compared to β2AR. The presence of V230 in β1AR accounted in part for the lower affinity. In conclusion TMDV of the β1AR contributes in part to the low affinity binding site of β1AR.

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There are two binding sites on the β1-adrenoceptor (AR), β1H and β1L corresponding to high and low affinity binding sites respectively, which can be activated to cause cardiostimulation (reviewed Kaumann and Molenaar, 2008). Some β-blockers that block β1AR and β2ARs can activate β1LARs at higher concentrations than those required to cause blockade. The β2AR does not form a corresponding low affinity binding site (Baker et al 2002) and therefore we postulated that heterologous amino acids are responsible for the formation of β1LAR. Our aim was to investigate whether heterologous amino acids of transmembrane domain V (TMDV) of β1AR and β2ARs contribute to β1LAR. β1ARs, β2ARs and mutant β1ARs containing all (β1(β2TMDV)AR) or single amino acids of TMDV of the β2AR were prepared and stably expressed in Chinese Hamster Ovary cells. Concentration-effect curves for cyclicAMP accumulation were carried out for (-)-CGP12177 or (-)-isoprenaline in the absence or presence of (-)-bupranolol. _______________________________________________________________________ (-)-CGP 12177 (-)-Bupranolol affinity (pKB) pEC50 vs (-)-CGP 12177 vs (-)-isoprenaline _______________________________________________________________________ β1AR 8.00 ± 0.11 (11) 7.23 ± 0.23 (5) 9.52 ± 0.28 (5) β2AR (high density) 9.24 ± 0.14 (5) 9.82 ± 0.52 (8) xPaulxxxxxxx β2AR (low density) no effect β1(β2TMV)AR 8.86 ± 0.10 (15) 8.06 ± 0.17 (8) 9.08 ± 0.22 (6) β1(V230I)AR 9.07 ± 0.07 (10) 7.64 ± 0.12 (8) 9.36 ± 0.28 (9) β1(R222Q)AR 8.09 ± 0.29 (6) 7.33 ± 0.23 (5) 9.36 ± 0.08 (6) β1(V230A)AR 7.59 ± 0.09 (6) 7.32 ± 0.24 (4) 8.62 ± 0.18 (5) _______________________________________________________________________ The potency of (-)-CGP12177 was higher at β2AR than at β1AR consistent with activation through a low affinity site at the β1AR (β1LAR) but not β2AR. The presence of V230 in β1AR accounted for the lower potency of (-)-CGP 12177. The affinity of (-)-bupranolol at β1AR and mutants was higher when determined with (-)-isoprenaline than with (-)-CGP 12177. The affinity of (-)-bupranolol determined against (-)-CGP 12177 was lower at β1AR compared to β2AR. The presence of V230 in β1AR accounted in part for the lower affinity. In conclusion V230 of the β1AR contributes in part to the low affinity binding site of β1AR. Baker JG, Hall IP, Hill SJ (2002). Pharmacological characterization of CGP12177 at the human β2-adrenoceptor. Br J Pharmacol 137, 400−408 Kaumann AJ, Molenaar P (2008) The low-affinity site of the β1-adrenoceptor and its relevance to cardiovascular pharmacology. Pharmacol Ther 118, 303-336

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‘MBA fever’ in China needs to be understood in the wider context of forces driving structural change in China’s relation to the global knowledge economy. The rise of a ‘new middle class’ in China is connected to the new claims for cultural leadership of an emergent ‘creative class’, which generates new issues about the relevance of the MBA in China, in terms of its relevance to Chinese economic circumstances, and its flexibility and capacity to respond to accumulation strategies that emphasise innovation, creativity and entrepreneurship.

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BACKGROUND AND PURPOSE It has been proposed that BRL37344, SR58611 and CGP12177 activate b3-adrenoceptors in human atrium to increase contractility and L-type Ca2+ current (ICa-L). b3-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the b1-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective b-adrenoceptor subtype antagonists to clarify cardiostimulant b-adrenoceptor subtypes in human atrium. EXPERIMENTAL APPROACH Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on ICa-L. Contractile effects were determined on right atrial trabeculae. KEY RESULTS BRL37344 increased force which was antagonized by blockade of b1- and b2-adrenoceptors but not by blockade of b3-adrenoceptors with b3-adrenoceptor-selective L-748,337 (1 mM). The b3-adrenoceptor agonist SR58611 (1 nM–10 mM) did not affect atrial force. BRL37344 and SR58611 did not increase ICa-L at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and ICa-L at both 24°C and 37°C which was prevented by (-)-bupranolol (1–10 mM), but not L-748,337. CONCLUSIONS AND IMPLICATIONS We conclude that the inotropic responses to BRL37344 are mediated through b1- and b2-adrenoceptors. The inotropic and ICa-L responses to (-)-CGP12177 are mediated through the low affinity site b1L-adrenoceptor of the b1-adrenoceptor. b3-adrenoceptor-mediated increases in ICa-L are restricted to low temperatures. Human atrial b3-adrenoceptors do not change contractility and ICa-L at physiological temperature.

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This article examines the role of copyrights in contemporary media literacies. It argues that, provided they are ethical, young people’s engagement with text should occur in environments that are as free from restriction as possible. Discussion of open culture ecologies and the emergent education commons is followed by a theorisation of both literacy and copyrights education as forms of epistemology: that is, as effects of knowledge producing discourses and practices. Because Creative Commons licenses respect and are based on existing copyright laws, a brief overview of traditional copyrights for educators is first provided. We then describe the voluntary Creative Commons copyright licensing framework (“some rights reserved”) as an alternative to conventional “all rights reserved” models. This is followed by an account of a series of workshop activities on copyrights and Creative Commons conducted by the authors in the media literacy classes of a preservice teacher education program in Queensland, Australia. It provides one example of a practical program on critical copyrights approaches, which may be adapted and used by other school and higher education institutions.

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The term Design is used to describe a wide range of activities. Like the term innovation, it is often used to describe both an activity and an outcome. Many products and services are often described as being designed, as they describe a conscious process of linking form and function. Alternatively, the many and varied processes of design are often used to describe a cost centre of an organisation to demonstrate a particular competency. However design is often not used to describe the ‘value’ it provides to an organisation and more importantly the ‘value’ it provides to both existing and future customers. Design Led Innovation bridges this gap. Design Led Innovation is a process of creating a sustainable competitive advantage, by radically changing the customer value proposition. A conceptual model has been developed to assist organisations apply and embed design in a company’s vision, strategy, culture, leadership and development processes.

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This paper examines the linkages between diversity management (DM), innovation and high performance in social enterprises. These linkages are explicated beyond traditional framing of DM limited to workforce composition, to include discussions of innovation through networked diversity practices; reconciliation; and funding options. The paper draws upon a UK-based national survey and the case study data. Multiple data collection methods were used, including semi-structured interviews, questionnaires and workshops with participant observation. NVivo and SPSS software packages were utilized in order to analyse the qualitative and quantitative data, respectively. We used thematic coding and cropping techniques in analysing the case studies in the paper. A broad range of conflicting and supporting literature was enfolded into the conversations and discussion. The paper demonstrates that social enterprises exhibit unique characteristics in terms of size and location, as well as their double remit to add value both economically and socially. As a conclusion, we argue for social enterprises to consider options for DM in the interests of maximization of innovation and business performance. We contend that further research is needed to describe how social entrepreneurs draw upon their various ‘diversity resources’ in the process of innovation

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The question posed in this chapter is: To what extent does current education theory and practice prepare graduates for the creative economy? We first define what we mean by the term creative economy, explain why we think it is a significant point of focus, derive its key features, describe the human capital requirements of these features, and then discuss whether current education theory and practice are producing these human capital requirements. The term creative economy can be critiqued as a shibboleth, but as a high level metaphor, it nevertheless has value in directing us away from certain sorts of economic activity and toward other kinds. Much economic activity is in no way creative. If I have a monopoly on some valued resource, I do not need to be creative. Other forms of economic activity are intensely creative. If I have no valued resources, I must create something that is valued. At its simplest and yet most profound, the idea of a creative economy suggests a capacity to compete based on engaging in a gainful activity that is different from everyone else’s, rather than pursuing the same endeavor more competitively than everyone else. The ability to differentiate on novelty is key to the concept of creative economy and key to our analysis of education for this economy. Therefore, we follow Potts and Cunningham (2008, p. 18) and Potts, Cunningham, Hartley, and Ormerod (2008) in their discussion of the economic significance of the creative industries and see the creative economy not as a sector but as a set of economic processes that act on the economy as a whole to invigorate innovation based growth. We see the creative economy as suffused with all industry rather than as a sector in its own right. These economic processes are essentially concerned with the production of new ideas that ultimately become new products, service, industry sectors, or, in some cases, process or product innovations in older sectors. Therefore, our starting point is that modern economies depend on innovation, and we see the core of innovation as new knowledge of some kind. We commence with some observations about innovation.

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In this chapter, we describe and explore social relationship patterns associated with outstanding innovation. In doing so, we draw upon the findings of 16 in-depth interviews with award-winning Australian innovators from science & technology and the creative industries. The interviews covered topics relating to various influences on individual innovation capacity and career development. We found that for all of the participants, innovation was a highly social process. Although each had been recognised individually for their innovative success, none worked in isolation. The ability to generate innovative outcomes was grounded in certain types of interaction and collaboration. We outline the distinctive features of the social relationships which seem to be important to innovation, and ask which ‘social network capabilities’ might underlie the ability to create an optimal pattern of interpersonal relationships. We discuss the implications of these findings for universities, which we argue play a key role in the development of nascent innovators.