Facilitating Active Learning in Large Lecture Courses: the Flipped Method

For faculty teaching large lecture-based courses, it is often a struggle to envision how to successfully execute the flipped classroom method when barriers such as technology or classroom constraints exist. In this session, participants will learn about strategies that can be used to transition a large lecture course into a flipped classroom. The session will draw largely on the experiences of the presenter in implementing case studies and the flipped classroom method in a large (250+ students) Introductory Biology class, but the approach is broadly applicable to any discipline. Tools for preparing original didactic videos and strategies for presenting case studies will be discussed. The session will also examine how the flipped classroom has changed teaching and learning habits and experiences, for both faculty and students

Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia

The leukemogenic effects of Myc drive recurrent trisomy in a mouse model of acute myeloid leukemia

Identifying rare cell populations in comparative flow cytometry

Abstract. Multi-channel, high throughput experimental methodologies for flow cytometry are transforming clinical immunology and hematology, and require the development of algorithms to analyze the highdimensional, large-scale data. We describe the development of two combinatorial algorithms to identify rare cell populations in data from mice with acute promyelocytic leukemia. The flow cytometry data is clustered, and then samples from the leukemic, pre-leukemic, and Wild Type mice are compared to identify clusters belonging to the diseased state. We describe three metrics on the clustered data that help in identifying rare populations. We formulate a generalized edge cover approach in a bipartite graph model to directly compare clusters in two samples to identify clusters belonging to one but not the other sample. For detecting rare populations common to many diseased samples but not to the Wild Type, we describe a clique-based branch and bound algorithm. We provide statistical justification of the significance of the rare populations

Duplications of proximal 16q flanked by heterochromatin are not euchromatic variants and show no evidence of heterochromatic position effect

Extra euchromatic material was found within the major heterochromatic block of chromosome 16 (16qh) in one de novo case and seven members of two families. In contrast to the euchromatic variants of chromosome 9 (9qh), which are derived from pericentromeric euchromatin, molecular cytogenetics confirmed that these duplications were of 16q11.2-->q12.2 in the de novo case, of 16q11.2-->q13 in three members of family 1 and 16q11.2-->q12.1 in four members of family 2. The duplication had arisen as a post-zygotic mitotic event in the mother of family 1 and been transmitted paternally in family 2. An insertional mechanism of origin is proposed for the duplications in case 1 and family 1. Expression at the 16q13 matrix metalloproteinase-2 (MMP2)locus in families 1 and 2 was proportional to genomic copy number and not therefore consistent with position effect silencing due to the flanking blocks of heterochromatin. We conclude that proximal 16q duplications within 16qh are not novel euchromatic variants but associated with a variable phenotype including developmental delay, speech delay, learning difficulties and behavioural problems. The behavioural problems in families ascertained through affected children are much less severe than those encountered in previous patients ascertained as adults

Rara haploinsufficiency modestly influences the phenotype of acute promyelocytic leukemia in mice

RARA (retinoic acid receptor alpha) haploinsufficiency is an invariable consequence of t(15;17)(q22;q21) translocations in acute promyelocytic leukemia (APL). Retinoids and RARA activity have been implicated in hematopoietic self-renewal and neutrophil maturation. We and others therefore predicted that RARA haploinsufficiency would contribute to APL pathogenesis. To test this hypothesis, we crossed Rara+/− mice with mice expressing PML (promyelocytic leukemia)-RARA from the cathepsin G locus (mCG-PR). We found that Rara haploinsufficiency cooperated with PML-RARA, but only modestly influenced the preleukemic and leukemic phenotype. Bone marrow from mCG-PR+/− × Rara+/− mice had decreased numbers of mature myeloid cells, increased ex vivo myeloid cell proliferation, and increased competitive advantage after transplantation. Rara haploinsufficiency did not alter mCG-PR–dependent leukemic latency or penetrance, but did influence the distribution of leukemic cells; leukemia in mCG-PR+/− × Rara+/− mice presented more commonly with low to normal white blood cell counts and with myeloid infiltration of lymph nodes. APL cells from these mice were responsive to all-trans retinoic acid and had virtually no differences in expression profiling compared with tumors arising in mCG-PR+/− × Rara+/+ mice. These data show that Rara haploinsufficiency (like Pml haploinsufficiency and RARA-PML) can cooperate with PML-RARA to influence the pathogenesis of APL in mice, but that PML-RARA is the t(15;17) disease-initiating mutation