Daniel W. Miller

Radiation therapy dosimetry reviews by the centers for radiological physics

Abstract Six Centers for Radiological Physics (CRP) have performed over 250 dosimetric site reviews at institutions participating in the Division of Cancer Control and Rehabilitation therapy networks and/or as affiliates in Oncology Group Clinical trials. For the initial site visits, institution stated output calibration was within ±3% of that measured by the CRPs for 87 % of the therapy machines reviewed. The accuracy of methods utilized in calculating tumor dose were assessed by using a set of reference cases of varying complexity. At the time of the first visit, 90% of the calculated doses for these reference cases were within ±5% of that prescribed by the CRPs. Other parameters, important for the accurate delivery of prescribed dose, were also checked as part of the review protocol. Many institutions have received multiple reviews and a significant reduction in the variance of machine calibration and calculated tumor dose for the reference cases is evident.

A mutation in Drosophila Aldolase causes temperature-sensitive paralysis, shortened lifespan, and neurodegeneration

We describe the characterization of m4, an autosomal recessive, temperature-sensitive paralytic mutant in Drosophila that is associated with shortened lifespan and neurodegeneration. Deletion mapping places the mutation in the gene encoding the glycolytic enzyme, Aldolase. The mutant enzyme contains a single amino acid substitution, which results in decreased steady-state levels of Aldolase with a consequent reduction in adenosine triphosphate (ATP) levels. Transgenic-rescue experiments with a genomic construct containing the entire Aldolase gene confirm that paralysis, reduced lifespan, and neurodegeneration all result from the same mutation. Tissue-specific rescue and RNA interference (RNAi) knockdown experiments indicate that Aldolase function (and presumably glycolysis) is important both in neurons and in glia for normal lifespan and neuronal maintenance over time. Impaired glycolysis in neurons can apparently be rescued in part by glycolytically active glia. However, this rescue may depend on the exact physiological state of the neurons and may also vary in different subsets of neurons. Further studies of m4 and related mutants in Drosophila should help elucidate the connections between energy production and utilization in glia and neurons and lead to better understanding of how metabolic defects impair neuronal function and maintenance.