This article reports on the design, implementation, and usage of the CourseMarker (formerly known as CourseMaster) courseware Computer Based Assessment (CBA) system at the University of Nottingham. Students use CourseMarker to solve (programming) exercises and to submit their solutions. CourseMarker returns immediate results and feedback to the students. Educators author a variety of exercises that benefit the students while offering practical benefits. To date, both educators and students have been hampered by CBA software that has been constructed to assess text-based or multiple-choice answers only. Although there exist a few CBA systems with some capability to automatically assess programming coursework, none assess Java programs and none are as flexible, architecture-neutral, robust, or secure as the CourseMarker CBA system.
We are interested in the allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs). We have postulated that the anthelmintic morantel (Mor) positively modulates (potentiates) rat ␣32 receptors through a site located at the (ϩ)/␣(Ϫ) interface that is homologous to the canonical agonist site (J Neurosci 29: 8734 -8742, 2009). On this basis, we aimed to determine the site specificity by studying differences in modulation between ␣32 and ␣42 receptors. We also compared modulation by Mor with that of the related compound oxantel (Oxa). Whereas Mor and Oxa each potentiated ␣32 receptors 2-fold at saturating acetylcholine (ACh) concentrations, Mor had no effect on ␣42 receptors, and Oxa inhibited AChevoked responses. The inhibition was noncompetitive, but not due to open channel block. Furthermore, the nature and extent of modulation did not depend on subunit stoichiometry. We studied six positions at the ␣(Ϫ) interface that differ between ␣3 and ␣4. Two positions (␣3Ile57 and ␣3Thr115) help mediate the effects of the modulators but do not seem to contribute to specificity. Mutations in two others (␣3Leu107 and ␣3Ile117) yielded receptors with appreciable ␣4-character; that is, Mor potentiation was reduced compared with wild-type ␣32 control and Oxa inhibition was evident. A fifth position (␣3Glu113) was unique in that it discriminated between the two compounds, showing no change in Mor potentiation from control but substantial Oxa inhibition. Our work has implications for rational drug design for nicotinic receptors and sheds light on mechanisms of allosteric modulation in nAChRs, especially the subtle differences between potentiation and inhibition.
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