Perinatal Hypoxia-Ischemia Disrupts Striatal High-Affinity [ 3 H]Glutamate Uptake into Synaptosomes

: We examined the impact of hypoxia-ischemia on high-affinity [ 3 H]glutamate uptake into a synaptosomal fraction prepared from immature rat corpus striatum. In 7-day-old pups the right carotid artery was ligated, and pups were exposed to 8% oxygen for 0, 0.5, 1, or 2.5 h, and allowed to recover for up to 24 h before they were killed. High-affinity glutamate uptakes in striatal synaptosomes derived from tissue ipsilateral and contralateral to ligation were compared. After 1 h of hypoxia plus ischemia, high-affinity glutamate uptake in the striatum was reduced by 54 ± 13% compared with values from the opposite (nonischemic) side of the brain (p < 0.01, t test versus ligates not exposed to hypoxia). There were similar declines after 2.5 h of hypoxiaischemia. Activity remained low after a 1 h recovery period in room air, but after 24 h of recovery, high-affinity glutamate uptake was equal bilaterally. Kinetic analysis revealed that loss of activity could be attributed primarily to a 40% reduction in the number of uptake sites. Hypoxia alone had no effect on high-affinity glutamate uptake although it reduced synaptosomal uptake of [ 3 H]3,4-dihydroxyphenyl-ethylamine. Addition of 1 mg/ml of bovine serum albumin to the incubation medium preferentia'ly stimulated high-affinity glutamate uptake in hypoxic-ischemic brain compared with its effects in normal tissue. These studies demonstrate that hypoxia-ischemia reversibly inhibits high-affinity glutamate uptake and this occurs earlier than the time required to produce neuronal damage in the model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66361/1/j.1471-4159.1986.tb00803.x.pd

The Role of Organizational Competences in the Evolution of Business Models

International audienceThis paper presents the use of a conceptual framework designed for the management of organizational competences to contribute to the evolution of the business model of an enterprise. The framework, developed based on a detailed review of the history of the car manufacturer Toyota, was used for a Delphi study and an action-research applied in the furniture industry. The results suggest that it is applicable for ex-post analysis of organizational changes, as well as a strategy planning tool

Long-term correction of diabetes in rats after lentiviral hepatic insulin gene therapy

Aims/hypothesis: Type 1 diabetes results from the autoimmune destruction of pancreatic beta cells. Exogenous insulin therapy cannot achieve precise physiological control of blood glucose concentrations, and debilitating complications develop. Lentiviral vectors are promising tools for liver-directed gene therapy. However, to date, transduction rates in vivo remain low in hepatocytes, without the induction of cell cycling. We investigated long-term transgene expression in quiescent hepatocytes in vitro and determined whether the lentiviral delivery of furin-cleavable insulin to the liver could reverse diabetes in rats. Materials and methods: To improve transduction efficiency in vitro, we optimised hepatocyte isolation and maintenance protocols and, using an improved surgical delivery method, delivered furin-cleavable insulin alone or empty vector to the livers of streptozotocin-induced diabetic rats by means of a lentiviral vector. Rats were monitored for changes in body weight and blood glucose, and intravenous glucose tolerance tests were performed. Expression of insulin was determined by RT-PCR, immunohistochemistry and electron microscopy. Results: We achieved long-term transgene expression in quiescent hepatocytes in vitro (87 ± 1.2% transduction efficiency), with up to 60 ± 3.2% transduction in vivo. We normalised blood glucose for 500 days-a significantly longer period than previously reported-making this the first successful study using a lentiviral vector. This procedure resulted in the expression of genes encoding several beta cell transcription factors, some pancreatic endocrine transdifferentiation, hepatic insulin storage in granules, and restoration of glucose tolerance. Liver function tests remained normal. Importantly, pancreatic exocrine transdifferentiation did not occur. Conclusions/interpretation: Our data suggest that this regimen may ultimately be employed for the treatment of type 1 diabetes

Absorptive capacity and innovation: When is it better to cooperate?

Cooperation can benefit and hurt firms at the same time. An important question then is: when is it better to cooperate? And, once the decision to cooperate is made, how can an appropriate partner be selected? In this paper we present a model of inter-firm cooperation driven by cognitive distance, appropriability conditions and external knowledge. Absorptive capacity of firms develops as an outcome of the interaction between absorptive R&D and cognitive distance from voluntary and involuntary knowledge spillovers. Thus, we offer a revision of the original model by Cohen and Levinthal (Econ J 99(397):569-596, 1989), accounting for recent empirical findings and explicitly modeling absorptive capacity within the framework of interactive learning. We apply that to the analysis of firms' cooperation and R&D investment preferences. The results show that cognitive distance and appropriability conditions between a firm and its cooperation partner have an ambiguous effect on the profit generated by the firm. Thus, a firm chooses to cooperate and selects a partner conditional on the investments in absorptive capacity it is willing to make to solve the understandability/novelty trade-off. © 2014 Springer-Verlag Berlin Heidelberg

“Happy accidents”: innovation-driven opportunities and perspectives for development in the knowledge economy

From Development as Democracy to Innovation as Development: Current local, regional, and global economic and financial conditions and trends make the need to trigger, catalyze and accelerate high quantity and quality entrepreneurial initiatives that are based on high quality and quantity innovations. Given the uncertainty and change inherent in the innovation process, management must develop skills and understanding of the process: a method for managing the disruption. Technology changes the way society functions. The dramatic advances in technology over recent decades have collaterally precipitated wide sweeping and profound change to the functioning of almost every form of human exchange, the world over. Income inequality in the US has being growing since the late 1970s, but easy credit and rising asset prices had allowed American households to increase financial leverage to finance consumption. Now an increasing number of academics and intellectuals recognize that the growing income inequality is one of the key aspects behind the financial crash. The first step in understanding how the income re-distribution can lead to innovation and help an economy move from a stagnant state into a new sustainable economic growth path is to understand how long-term trends in rising and falling income inequality affect the market environment that firms must survive in. In the late twentieth and the beginning of the twenty-first century, numerous scholars and practitioners such as Peter Drucker have identified knowledge as a crucial and most important key input and output factor of economic activity. The knowledge-based economy can be characterized as fractal. It is non-linear, unstable, and stochastic. From Development as Democracy to Innovation as Development: and back to from Innovation as Development to Development as Democracy

External vs Internal Determinants of Firm Technology Strategy: Evidence from the Polish Services Sector

The authors use the insights from strategy research and innovation studies to address two principal questions regarding the technology strategy of a firm: what are the distinct elements of technology strategy and what are the strategy determinants? Equipped with Zahra's (1996) concept of measuring technology strategy, we analyze data from two runs of the Community Innovation Survey for Polish service firms. They propose a set of indicators reflecting four principal fields of technology strategy: pioneer-posture, R&D efforts, technology portfolio, and monitoring activities. Interactions between the strategic variables are analyzed and their determinants are assessed. The results suggest that technology strategies are determined by both factors external to the firm, and by the hitherto less stressed in the CIS-based empirical literature, internal factors. The role of internal factors increases with the macroeconomic environment becoming less favourable