Making strategy and organization compatible

This book argues that for many companies organisation is designed to achieve operational optimization and may be in conflict with strategic objectives. Managers may not share similar decision criteria and this may facilitate or hinder the fulfilment of certain strategies. The role of top managers is to shape to a large extent the ability of the organisational system to implement and achieve strategic objectives. This book provides breakthrough thinking on these issues by two leading academic thinkers

4-epi-Isofagomine derivatives as pharmacological chaperones for the treatment of lysosomal diseases linked to β-galactosidase mutations: Improved synthesis and biological investigations.

(5aR)-5a-C-pentyl-4-epi-isofagomine 1 is a powerful inhibitor of lysosomal β-galactosidase and a remarkable chaperone for mutations associated with GM1-gangliosidosis and Morquio disease type B. We report herein an improved synthesis of this compound and analogs (5a-C-methyl, pentyl, nonyl and phenylethyl derivatives), and a crystal structure of a synthetic intermediate that confirms its configuration resulting from the addition of a Grignard reagent. These compounds were evaluated as glycosidase inhibitors and their potential as chaperones for mutant lysosomal galactosidases determined. Based on these results and on docking studies, the 5-C-pentyl derivative 1 was selected as the optimal structure for further investigations: this compound induces the maturation of mutated β-galactosidase in fibroblasts of a GM1-gangliosidosis patient and promote the decrease of keratan sulfate and oligosaccharide load in patient cells. Compound 1 is clearly capable of restoring β-galactosidase activity and of promoting maturation of the protein, which should result in significant clinical benefit. These properties strongly support the development of compound 1 for the treatment of GM1-gangliosidosis and Morquio disease type B patients harboring β-galactosidase mutations sensitive to pharmacological chaperoning

Public organizations, stakeholders and the construction of publicness. Claims and defence of authority in public action

International audienceThis article seeks to highlight the conditions in which organizations with different levels of ‘publicness’ interact in the framework of policy-making. In France, decision making and implementation is shared among public, semi-public and private organizations. The specific responsibility and influence of public organizations within institutional collective action however is a source of ambiguity. It becomes therefore a matter of political authority for public organizations to invest in the structuring of public problems and policies. The case analysed here shows that the publicness of implemented policies is a construction which stakeholders may try to influence. Responses by public organizations show that publicness does not only relate to the plurality of organizational forms but also to the existence of a form of hierarchy within systems of governance themselves