While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiacfibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.
This paper intends to shed some light on strategies and power resources of subsidiary managers and employee representatives involved in 'charter changes' and the implementation of 'best practices' developed elsewhere. Research shows that local managers face a dilemma in that they need both internal legitimacy (within the MNC itself) and external legitimacy (within the local context). We argue that the power resources key actors draw on in the (internal) decision-making processes of 'charter changes' are intertwined with certain (external) national business system (NBS) characteristics, an aspect often neglected in North-American research about MNCs.We identify three key influences, which restrain or empower local management and employees in their ability to make strategic choices and gain power within the MNC.They are (1) the overall strategic approach of the multinational group, (2) the strategic position and the economic performance of the subsidiary itself and (3) the degree of institutional embeddedness of the subsidiary in the host country. Comparative minicase studies are used to illustrate the effect of local management and employee representatives' empowerment on their ability to retain skills and work practices supportive of a diversified quality production process in the face of MNC pressure to adopt global 'best practices' based on more standardised production processes.
This paper seeks to examine empirically the extent to which actors in subsidiaries of multinational companies (MNCs) are able to exercise some choice in the face of global pressures from the MNC headquarters (HQ). We argue that managerial practices in MNCs are not the result of a simple imposition of a global or a MNC organisational rationality but are subject to an interactive process, where differing contextual rationalities come into play. Using data from MNC subsidiaries in Britain and Germany, the paper compares the power resources and strategic choices of subsidiary level actors and shows the ways in which they seek to influence global strategy implementation as it affects local work systems. We investigate the different abilities of German and British managers to shape global restructuring processes in their local organisational contexts and conclude that national contexts impact on both the formulation of parent company strategies via a home country rationality and on the implementation of global strategies via a host country rationality. There are greater national barriers to a MNC policy of convergence based on standardized products and processes in Germany than in the UK.
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