992 resultados para Modulation strategy


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The development of health policy is recognized as complex; however, there has been little development of the role of agency in this process. Kingdon developed the concept of policy entrepreneur (PE) within his ‘windows’ model. He argued inter-related ‘policy streams' must coincide for important issues to become addressed. The conjoining of these streams may be aided by a policy entrepreneur. We contribute by clarifying the role of the policy entrepreneur and highlighting the translational processes of key actors in creating and aligning policy windows. We analyse the work in London of Professor Sir Ara Darzi as a policy entrepreneur. An important aspect of Darzi's approach was to align a number of important institutional networks to conjoin related problems. Our findings highlight how a policy entrepreneur not only opens policy windows but also yokes together a network to make policy agendas happen. Our contribution reveals the role of clinical leadership in health reform.

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Established firms tend to pursue incremental innovation by modifying and refining their existing products and processes rather than developing radical innovations. In the face of resistance to change and incumbent inertia, which prevent the generation of novelty, established firms have turned towards corporate entrepreneurship as a means of exploiting knowledge accumulated within its own boundaries and exploring external markets. This paper focuses on one mode of corporate entrepreneurship, corporate incubation, informed by a study of a Technology Incubator at Philips. An account of the history of the incubator traces its progress from its inception in 2002-2006 when further incubators were formed, building on this experience and focusing on lifestyle and healthcare technologies. We identify ways in which the Philips incubator represents an alternative selection environment that effectively simulated the venture capitalist model of entrepreneurial innovation. © 2009 Blackwell Publishing Ltd.

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We simultaneously recorded auditory evoked potentials (AEP) from the temporal cortex (TCx), the dorsolateral prefrontal cortex (dPFCx) and the parietal cortex (PCx) in the freely moving rhesus monkey to investigate state-dependent changes of the AEP. AEPs obtained during passive wakefulness, active wakefulness (AW), slow wave sleep and rapid-eye-movement sleep (REM) were compared. Results showed that AEP from all three cerebral areas were modulated by brain states. However, the amplitude of AEP from dPFCx and PCx significantly appeared greater attenuation than that from the TCx during AW and REM. These results indicate that the modulation of brain state on AEP from all three cerebral areas investigated is not uniform, which suggests that different cerebral areas have differential functional contributions during sleep-wake cycle. (C) 2002 Elsevier Science Ireland Ltd.. All rights reserved.

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Socio-economic Monitoring (SocMon) is an approach and set of tools for conducting socio-economic monitoring of changes in coastal communities. Key considerations included: importance of local partnerships; government and civil society partnerships; emphasis of adapting SocMon to local needs and priorities; capacity building; engaging with local stakeholders; inter and intra-regional collaboration; importance of language; and importance of language.

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This was a follow up to the workshop held in October, 2014. This second workshop consolidated findings an and recommendations and highlighted the importance of cooperation between Department of Fisheries (DoF) and non-state actors.

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Many ionotropic receptors are modulated by extracellular H+. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine-evoked currents (I-Gly) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H+ modulated both the mIPSCs and I-Gly, biphasically, although it activated an amiloride-sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and I-Gly, while increasing external pH reversibly potentiated these parameters. Blockade of acid-sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H+ on either mIPSCs or I-Gly, H+ shifted the EC50 of the glycine concentration-response curve from 49.3 +/- 5.7 muM at external pH 7.4 to 131.5 +/- 8.1 muM at pH 5.5, without altering the Cl- selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal I-Gly, suggesting a competitive inhibition of I-Gly by H+. Both Zn2+ and H+ inhibited I-Gly. However, H+ induced no further inhibition of I-Gly in the presence of a saturating concentration of Zn2+. In addition, H+ significantly affected the kinetics of glycinergic mIPSCs and I-Gly. It is proposed that H+ and/or Zn2+ compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and I-Gly. Moreover, binding of H+ induces a global conformational change in GlyR, which closes the GlyR Cl- channel and results in the acceleration of the seeming desensitization of IGly as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound I-Gly. H+ also modulated the glycine cotransmitter, GABA-activated current (I-GABA). Taken together, the results support a 'conformational coupling' model for H+ modulation of the GlyR and suggest that W may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.

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The characterization of acid-sensing ion channel (ASIC)-like currents has been reported in hippocampal neurons in primary culture. However, it is suggested that the profile of expression of ASICs changes in culture. In this study, we investigated the properties of proton-activated current and its modulation by extracellular Ca2+ and Zn2+ in neurons acutely dissociated from the rat hippocampal CA1 using conventional whole-cell patch-clamp recording. A rapidly decaying inward current and membrane depolarization was induced by exogenous application of acidic solution. The current was sensitive to the extracellular proton with a response threshold of pH 7.0-6.8 and the pH(50) Of 6.1, the reversal potential close to the Na+ equilibrium potential. It had a characteristic of acid-sensing ion channels (ASICs) as demonstrated by its sensitivity to amiloride (IC50 = 19.6 +/- 2.1 muM). Either low [Ca2+](0) or high [Zn2+](0) increased the amplitude of the current. All these characteristics are consistent with a current mediated through a mixture of homomeric ASIC1a and heteromeric ASIC1a + 2a channels and closely replicate many of the characteristics that have been previously reported for hippocampal neurons cultured for a week or more, indicating that culture artifacts do not necessarily flaw the properties of ASICs. Interestingly, we found that high [Zn2+] (>10(-4) M) slowed the decay time constant of the ASIC-like current significantly in both acutely dissociated and cultured hippocampal neurons. In addition, the facilitating effects of low [Ca2+](0) and high [Zn2+](0) on the ASIC-like current were not additive. Since tissue acidosis, extracellular Zn elevation and/or Ca2+ reduction occur concurrently under some physiological and/or pathological conditions, the present observations suggest that hippocampal ASICs may offer a novel pharmacological target for therapeutic invention. (C) 2004 Elsevier B.V. All rights reserved.

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Detailed investigations are undertaken, for the first time, of the transmission performance of recently proposed novel Adaptively Modulated Optical OFDM (AMOOFDM) modems using Subcarrier Modulation (AMOOFDM-SCM) in single-channel, SMF-based IMDD links without optical amplification and chromatic dispersion compensation. The cross-talk effect induced by beatings among subcarriers of various types is a crucial factor limiting the maximum achievable AMOOFDM-SCM performance. By applying single sideband modulation and/or spectral gapping to AMOOFDM-SCM, three AMOOFDM-SCM designs of varying complexity are proposed, which achieve >60Gb/s signal transmission over 20 km, 40 km and 60 km. Such performances are >1.5 times higher than those supported by conventional AMOOFDM modems.