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Helping Eastern students to master Western critical thinking
YiChing Jean Chiu,John Cowan 서울대학교 교육연구소 2012 Asia Pacific Education Review Vol.13 No.1
It is possible that some of the problems that confront Eastern learners when they are asked to engage in critical thinking come from the misleading association of the title with criticising negatively and even with disagreeing. In some other educational situations, careful choice of first language titles for concepts so that they do not introduce difficulties for learners has proved fruitful in easing acquaintance with a new concept. Since the definitions of critical thinking emphasise the central role of reasoning in this process and make no explicit mention of disagreement or fault finding, there seems potential in a pedagogical approach to the development of the ability for critical thinking which focuses on identifying, considering and presenting reasons-and perhaps renaming the process, even if only temporarily, accordingly. Such an approach has been devised, in response to the difficulties that Taiwanese students have met when engaging with critical thinking. It has been piloted on one class in an online discussion forum in English as a Foreign Language. The outcomes of this pilot are encouraging and are presented at this stage for that reason.
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Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors
Zhang, Jianming,Adriá,n, Francisco J.,Jahnke, Wolfgang,Cowan-Jacob, Sandra W.,Li, Allen G.,Iacob, Roxana E.,Sim, Taebo,Powers, John,Dierks, Christine,Sun, Fangxian,Guo, Gui-Rong,Ding, Qiang,Okra Macmillan Publishers Limited. All rights reserved 2010 Nature Vol.463 No.7280
In an effort to find new pharmacological modalities to overcome resistance to ATP-binding-site inhibitors of Bcr–Abl, we recently reported the discovery of GNF-2, a selective allosteric Bcr–Abl inhibitor. Here, using solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry, we show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr–Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. These results show that therapeutically relevant inhibition of Bcr–Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.
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