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Ms Yu Chen

Research Assistant

Academic and research departments

Department of Chemical and Process Engineering.

My publications


Chen Y, Broad L, Phillips K, Zwart R (2011) Partial agonists for ±4²2 nicotinic receptors stimulate dopamine neuron firing with relatively enhanced maximal effects., Br J Pharmacol 165 (4) pp. 1006-1016 Wiley-Blackwell
Background and purpose.? Partial agonists selective for ±4²2 nicotinic acetylcholine receptors have been developed for smoking cessation based on the hypothesis that they induce weak activation of native ±4²2* receptors and inhibit effect of nicotine. However, the relative physiological effects of partial agonists are largely unknown. For instance, on neuronal functions where partial activation of a receptor pool is sufficient for the maximum response, i.e. where there is receptor reserve, partial agonists may become maximally effective. We assessed effects of ±4²2 partial agonists on the firing of dopamine neurons and evaluated the influence by receptor reserve. Experimental approach.? Six agonists with different relative maximal effects on recombinant human ±4²2 receptors were examined on the spontaneous firing rate of dopamine neurons in the ventral tegmental area. Key Results.? Agonists induced concentration-dependent increase in firing rate in a mecamylamine and DHßE, but not ±-conotoxin MII or methyllycaconitine-sensitive, manner, indicating predominant activation of native ±4²2* receptors. ±4²2 partial agonists, cytisine (21%) and TC-2559 (33%), increased the firing rate to 43 and 100% of the maximum, respectively, showing enhanced effects relative to full agonists. However, full agonists induced an additional depolarisation block of firing at high concentrations, revealing the presence of surplus receptors for the maximum increase of firing rate. Conclusions and implications.? Partial activation of all the receptors was sufficient for the maximum increase of firing rate in dopamine neurons, creating a receptor reserve and relatively enhanced effects of partial ±4²2 agonists by activating all receptors. The availability of native ±4²2* receptors may thus modulate physiological effects and therapeutic efficacies of ±4²2 partial agonists.
Chen Y, De S, Kernchen R, Moessner K (2012) Device discovery in future service platforms through SIP, pp. 1-5
This paper proposes an extension to Session Initiation Protocol (SIP) for contextualized service delivery in a service delivery platform (SDP) that enables device specific multimedia delivery. SIP separates between session establishment and description and is thus, amenable to be extended for advanced implementations which make it an ideal platform for service creation. Device specific multimedia delivery needs rich and flexible device descriptions, and our approach proposes advanced device descriptions through semantic technologies. The proposed SIP extensions have been implemented on a SIP Application Server which functions as SDP in IP Multimedia Subsystem (IMS). The validation of the proposed extensions is shown through an Android SIP client application that acts as a device browser and recommender for different multimedia services to users. An example device user agent (UA) application has also been implemented on a laptop.
de Filippi G, Mogg A, Phillips K, Zwart R, Sher E, Chen Y (2010) The subtype-selective nicotinic acetylcholine receptor positive allosteric potentiator 2087101 differentially facilitates neurotransmission in the brain, European Journal of Pharmacology 643 (2-3) pp. 218-224 Elsevier
Positive allosteric modulators of centrally expressed nicotinic acetylcholine receptors have therapeutic potentials in areas of cognition, motor function and reward. Several chemical classes of allosteric modulators that are selective for alpha7 nicotinic receptors have been characterised, but potentiators for the most widely expressed alpha4beta2 nicotinic receptor subtype are few and less defined, owing probably to the difficulty to achieve selectivity over other heteromeric receptor subtypes. 2087101 ((2-amino-5-keto)thiazole) is a potent potentiator of both alpha7 and alph4beta2 receptors and it has selectivity against the alpha3beta4 subtype, which may be responsible for the undesirable peripheral side effects. To further characterise its ability to differentiate between native nicotinic receptors, we examined the effects of 2087101 on alpha7, alpha4beta2* and alpha3beta4* receptor-mediated responses in the rat brain in electrophysiological and neurochemical experiments. 2087101 significantly potentiated agonist-induced, alpha7 and non-alpha7 receptor-mediated, GABAergic postsynaptic currents in cultured hippocampal neurones, but not the nicotine-stimulated [3H]noradrenaline release from hippocampal slices, which was primarily mediated by alpha3beta4* receptors, confirming its selectivity for alpha7 and alpha4beta2* receptors in native systems. 2087101 also significantly enhanced nicotine-stimulated firing increase in dopamine neurones of the ventral tegmental area, an effect that was dihydro-beta-erythroidine-sensitive and thereby mediated by alpha4beta2* nicotinic receptors. 2087101 can therefore enhance native nicotinic activities mediated by alpha7 and alpha4beta2*, but not alpha3beta4* receptors, showing its unique ability to discriminate between native heteromeric nicotinic receptor subtypes and its therapeutic potential for treating brain disorders by concurrent modulation of both alpha7 and alpha4beta2* nicotinic receptors.