Leveraging external knowledge in concept generation targeting architectural innovation

Mimeo, 201

Inside the Ambidextrous Organization: a multilevel analysis of the tensions and the integration dynamics

Mimeo, 200

Presence of circulating abnormal CD34+ progenitors in adult Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is related to the proliferation of cells, which are similar to Langerhans cells (LC) but possess many abnormal characteristics. Lesions are widespread and this fact suggests that LCH cells or their precursors are present in the blood of patients. In five adult patients, we have isolated and cultured CD34+ blood progenitors of dendritic cells. We studied their phenotype by flow cytometry and their functional properties in mixed culture with heterologous lymphocytes and with autologous lymphocytes in the presence of tri-nitro-phenyl antigen (TNP). The amount of CD34+ precursors was dramatically higher than controls but a high mortality occurred during the in vitro differentiation. The phenotype of surviving cells was similar to LC phenotype (CD1a+, CD83+, Lag+) but some of them expressed CD2. These cells were able to induce T cell proliferation in mixed culture. They could not initiate primary response to TNP, except in a patient treated with thalidomide. In our hands, these CD34+ cells may be precursors of LCH cells

Cardiomyocyte overexpression of neuronal nitric oxide synthase delays transition toward heart failure in response to pressure overload by preserving calcium cycling

International audienceBACKGROUND: Defects in cardiomyocyte Ca(2+) cycling are a signature feature of heart failure (HF) that occurs in response to sustained hemodynamic overload, and they largely account for contractile dysfunction. Neuronal nitric oxide synthase (NOS1) influences myocyte excitation-contraction coupling through modulation of Ca(2+) cycling, but the potential relevance of this in HF is unknown. METHODS AND RESULTS: We generated a transgenic mouse with conditional, cardiomyocyte-specific NOS1 overexpression (double-transgenic [DT]) and studied cardiac remodeling, myocardial Ca(2+) handling, and contractility in DT and control mice subjected to transverse aortic constriction (TAC). After TAC, control mice developed eccentric hypertrophy with evolution toward HF as revealed by a significantly reduced fractional shortening. In contrast, DT mice developed a greater increase in wall thickness (P<0.0001 versus control+TAC) and less left ventricular dilatation than control+TAC mice (P<0.0001 for both end-systolic and end-diastolic dimensions). Thus, DT mice displayed concentric hypertrophy with fully preserved fractional shortening (43.7+/-0.6% versus 30.3+/-2.6% in control+TAC mice, P<0.05). Isolated cardiomyocytes from DT+TAC mice had greater shortening, intracellular Ca(2+) transients, and sarcoplasmic reticulum Ca(2+) load (P<0.05 versus control+TAC for all parameters). These effects could be explained, at least in part, through modulation of phospholamban phosphorylation status. CONCLUSIONS: Cardiomyocyte NOS1 may be a useful target against cardiac deterioration during chronic pressure-overload-induced HF through modulation of calcium cycling

Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease

International audienceIntravascular hemolysis describes the relocalization of heme and hemoglobin (Hb) from erythrocytes to plasma. We investigated the concept that erythrocyte membrane microparticles (MPs) concentrate cell-free heme in human hemolytic diseases, and that hemeladen MPs have a physiopathological impact. Up to one-third of cell-free heme in plasma from 47 patients with sickle cell disease (SCD) was sequestered in circulating MPs. Erythrocyte vesiculation in vitro produced MPs loaded with heme. In silico analysis predicted that externalized phosphatidylserine (PS) in MPs may associate with and help retain heme at the cell surface. Immunohistology identified Hb-laden MPs adherent to capillary endothelium in kidney biopsies from hyperalbuminuric SCD patients. In addition, heme-laden erythrocyte MPs adhered and transferred heme to cultured endothelial cells, inducing oxidative stress and apoptosis. In transgenic SAD mice, infusion of hemeladen MPs triggered rapid vasoocclusions in kidneys and compromised microvascular dilation ex vivo. These vascular effects were largely blocked by heme-scavenging hemopexin and by the PS antagonist annexin-a5, in vitro and in vivo. Adversely remodeled MPs carrying heme may thus be a source of oxidant stress for the endothelium, linking hemolysis to vascular injury. This pathway might provide new targets for the therapeutic preservation of vascular function in SCD

A Conceptual Perspective on Knowledge Management and Boundary Spanning: Knowledge, Boundaries and Commons

International audienceBoundaries and transcending boundaries have become a major discussion topic in fields involved in the creation of value in Western economies. Quite often assimilated into physical and cultural limits, boundaries are presented as obstacles to entrepreneurial achievement. This entrepreneurial ability that unfolds in different fields-the economy of course, but also cultural activities, notably through a revolution of usages facilitated by internet business platforms. It seems pertinent to compare how commercial and non-commercial activities process information and accumulate knowledge. Boundaries must be crossed in order to diffuse knowledge and create innovation. But boundaries also act as a protection for scientific, technical, and cultural organisations and institutions. Boundaries are multiple and, in principle, objective between projects, organisations, types of knowledge, scientific disciplines, and of course between the various actors. But are they really all that objective? The succession of approaches towards knowledge management has a history (Snowden, 2002). A genealogy of the concepts and their success is available, testifying to the plasticity of knowledge boundaries. In this sense, our analysis presents boundaries as a construct that enables association between elements as much as separation. We begin by presenting a genealogy of the major concepts in the field of knowledge dissemination. We lay down the various terms that refer to knowledge boundaries, insisting, in particular, on the persistent misunderstanding about how the learning process leads to knowledge. This conceptual framework helps us distinguish two functions of a boundary-separation and elaboration. We will then go on to develop this distinction for commercial organisations, and finally for non-commercial organisations such as Wikipedia