Asssessing Higher Order Skills Using Simulations

<div>The alignment of assessment strategy with learning outcomes is important as it ensures the validity of any measurement obtained. Without the ability to assess higher order skills, online assessment will be unable to progress</div><div>beyond objective testing. Bennett’s (1998) vision of the future of assessment sees an increased use of simulations together with a blurring of the lines between assessment and teaching. This paper outlines a project that is taking</div><div>the first steps in this direction.</div><div>A system is being devised to allow an assessment engine and a simulation to communicate at a deep level to improve authoring capability and enable more complex assessments. The paper explores issues that have been addressed in the design of the communication interface and protocols. The higher order skills that can be assessed with the system are outlined with examples, using the cognitive process dimension of the revised version of Bloom’s taxonomy</div><div>produced by Anderson et al (2001)</div><div><br></div><div>Thomas, R., Ashton, H., Austin, B., Beevers, C., Edwards, D., & Milligan, C. (2004). Assessing Higher Order Skills using Simulations. Proceedings of Eighth International Computer Assisted Assessment Conference (pp417-427), Leicestershire, United Kingdom, Loughborough University.<br></div

Discovery of Imidazo[1,2‑<i>a</i>]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo­[1,2-<i>a</i>]­pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure–activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection