Designing an interactive laboratory experiment to investigate buoyancy

Laboratory classes provide a visual and practical way of supplementing traditional teaching through lectures and tutorial classes. A criticism of laboratories in our School is that they are largely based on demonstration with insufficient participation by students. This provided the motivation to create a new laboratory experiment which would be interactive, encourage student enthusiasm with the subject and improve the quality of student learning.

The topic of the laboratory is buoyancy. While this is a key topic in the first-year fluids module, the laboratory has been designed in such a way that prior knowledge of the topic is unnecessary and therefore it would be accessible by secondary school pupils. The laboratory climaxes in a design challenge. However, it begins with a simple task involving students identifying some theoretical background information using given websites. They then have to apply their knowledge by developing some equations. Next, given some materials (a sheet of tinfoil, card and blu-tack), they have to design a vessel to carry the greatest mass without sinking. Thus, they are given an open-ended problem and have to provide a mathematical justification for their design. Students are expected to declare the maximum mass for their boat in advance of it being tested to create a sense of competition and fun. Overall, the laboratory involves tasks which begin at a low level and progressively get harder, incorporating understanding, applying, evaluating and designing (with reference to Bloom’s taxonomy).

The experiment has been tested in a modern laboratory with wall-mounted screens and access to the internet. Students enjoyed the hands-on aspect and thought the format helped their learning.

The use of cheap materials which are readily available means that many students can be involved at one time. Support documentation has been produced, both for the student participants and the facilitator. The latter is given advice on how to guide the students (without simply giving them the answer) and given some warning about potential problems the students might have.

The authors believe that the laboratory can be adapted for use by secondary school pupils and hope that it will be used to promote engineering in an engaging and enthusing way to a wider audience. To this end, contact has already been made with the Widening Participation Unit at the University to gain advice on possible next steps.

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G₁ -S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1Amutant OCCC. Mol Cancer Ther; 15(7); 1472-84. Ó2016 AACR.

Low-dose salinomycin induces anti-leukemic responses in AML and MLL

Development of anti-cancer drugs towards clinical application is costly and inefficient. Large screens of drugs, efficacious for non-cancer disease, are currently being used to identify candidates for repurposing based on their anti-cancer properties. Here, we show that low-dose salinomycin, a coccidiostat ionophore previously identified in a breast cancer screen, has anti-leukemic efficacy. AML and MLLr cell lines, primary cells and patient samples were sensitive to submicromolar salinomycin. Most strikingly, colony formation of normal hematopoietic cells was unaffected by salinomycin, demonstrating a lack of hemotoxicity at the effective concentrations. Furthermore, salinomycin treatment of primary cells resulted in loss of leukemia repopulation ability following transplantation, as demonstrated by extended recipient survival compared to controls. Bioinformatic analysis of a 17-gene signature identified and validated in primary MLLr cells, uncovered immunomodulatory pathways, hubs and protein interactions as potential transducers of low dose salinomycin treatment. Additionally, increased protein expression of p62/Sqstm1, encoded for by one of the 17 signature genes, demonstrates a role for salinomycin in aggresome/vesicle formation indicative of an autophagic response.
Together, the data support the efficacy of salinomycin as an anti-leukemic at non-hemotoxic concentrations. Further investigation alone or in combination with other therapies is warranted for future clinical trial.