פרסומים

AbstractPurposeThis study investigates how senior science teachers viewed the effects of a Raising Test Scores policy and its implementation on instruction of higher order thinking (HOT), and on teaching thinking to students with low academic achievements.BackgroundThe study was conducted in the context of three concurrent policies advocating: (a) improving test scores; (b) developing students’ thinking and inquiry skills; and (c) narrowing achievement gaps.MethodologyData collection was based on 20 interviews with senior science teachers.ResultsThe findings show that the senior teachers? expectations regarding a ?new spirit? calling for instruction of inquiry and HOT throughout the system did not materialize under the high stakes testing regime. Test preparation did involve intense engagement with HOT tasks. However, under the regime of high stakes testing, instruction of HOT seemed to take the form of ?mechanical instruction?, implying rote learning and drilling students in answering HOT items, rather than teaching for thinking in a meaningful way.ConclusionIn the presence of the aggressive policy addressing the need to raise test scores, the goal of teaching students to think, as well as the more specific goal of teaching low-achieving students to think was compromised in a considerable way.

AbstractPurposeThis study investigates how senior science teachers viewed the effects of a Raising Test Scores policy and its implementation on instruction of higher order thinking (HOT), and on teaching thinking to students with low academic achievements.BackgroundThe study was conducted in the context of three concurrent policies advocating: (a) improving test scores; (b) developing students' thinking and inquiry skills; and (c) narrowing achievement gaps.MethodologyData collection was based on 20 interviews with senior science teachers.ResultsThe findings show that the senior teachers? expectations regarding a ?new spirit? calling for instruction of inquiry and HOT throughout the system did not materialize under the high stakes testing regime. Test preparation did involve intense engagement with HOT tasks. However, under the regime of high stakes testing, instruction of HOT seemed to take the form of ?mechanical instruction?, implying rote learning and drilling students in answering HOT items, rather than teaching for thinking in a meaningful way.ConclusionIn the presence of the aggressive policy addressing the need to raise test scores, the goal of teaching students to think, as well as the more specific goal of teaching low-achieving students to think was compromised in a considerable way.

Differentiation events contribute to phenotypic cellular heterogeneity within tumors and influence disease progression and response to therapy. Here, we dissect mechanisms controlling intratumoral heterogeneity within triple-negative basal-like breast cancers. Tumor cells expressing the cytokeratin K14 possess a differentiation state that is associated with that of normal luminal progenitors, and K14-negative cells are in a state closer to that of mature luminal cells. We show that cells can transition between these states through asymmetric divisions, which produce one K14(+) and one K14(-) daughter cell, and that these asymmetric divisions contribute to the generation of cellular heterogeneity. We identified several regulators that control the proportion of K14(+) cells in the population. EZH2 and Notch increase the numbers of K14(+) cells and their rates of symmetric divisions, and FOXA1 has an opposing effect. Our findings demonstrate that asymmetric divisions generate differentiation transitions and heterogeneity, and identify pathways that control breast cancer cellular composition.

channel, increasing sinuosity. Upstream, near the migrating knickzone channel gradients also increase, incision is more moderate and floods continue to overtop the banks, favoring meander chute cutoffs. The resulting channel has a downstream well-confined meandering segment and an upstream low-sinuosity segment. These new insights regarding spatial differences along an incising channel can improve interpretations of the evolution of ancient planforms and floodplains that responded to base-level decline.

CKIα ablation induces p53 activation, and CKIα degradation underlies the therapeutic effect of lenalidomide in a pre-leukemia syndrome. Here we describe the development of CKIα inhibitors, which co-target the transcriptional kinases CDK7 and CDK9, thereby augmenting CKIα-induced p53 activation and its anti-leukemic activity. Oncogene-driving super-enhancers (SEs) are highly sensitive to CDK7/9 inhibition. We identified multiple newly gained SEs in primary mouse acute myeloid leukemia (AML) cells and demonstrate that the inhibitors abolish many SEs and preferentially suppress the transcription elongation of SE-driven oncogenes. We show that blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, and induce apoptosis. Leukemia progenitors are selectively eliminated by the inhibitors, explaining their therapeutic efficacy with preserved hematopoiesis and leukemia cure potential; they eradicate leukemia in MLL-AF9 and Tet2(-/-);Flt3(ITD) AML mouse models and in several patient-derived AML xenograft models, supporting their potential efficacy in curing human leukemia.