Expression of the Androgen Receptor Governs Radiation Resistance in a Subset of Glioblastomas Vulnerable to Antiandrogen Therapy.

New approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and are reported to express steroid hormone receptors, we reasoned that signaling through the androgen receptor (AR) could mediate therapy resistance in GBM, much as it does in AR-positive prostate and breast cancers. We found that nearly half of GBM cell lines, patient-derived xenografts (PDX), and human tumors expressed AR at the transcript and protein level-with expression levels overlapping those of primary prostate cancer. Analysis of gene expression datasets also revealed that AR expression is higher in GBM patient samples than normal brain tissue. Multiple clinical-grade antiandrogens slowed the growth of and radiosensitized AR-positive GBM cell lines and PDXs in vitro and in vivo Antiandrogens blocked the ability of AR-positive GBM PDXs to engage adaptive transcriptional programs following radiation and slowed the repair of radiation-induced DNA damage. These results suggest that combining blood-brain barrier permeable antiandrogens with radiation may have promise for patients with AR-positive GBMs.

Simulating Imaging of Large Scale Radio Arrays on the Lunar Surface.

In recent years there has been a renewed interest in returning to the Moon for reasons both scientific and exploratory in nature. The Moon provides the perfect training ground for building large scale bases that one may apply to other planets like Mars. The existence of a radio quiet zone on the lunar far side has promise for early universe studies and exoplanet searches, while the near side provides a stable base that may be used to observe low frequency emissions from Earth's magnetosphere that may help gauge its response to incoming space weather. The construction of a large-scale radio array would provide large scientific returns as well as acting as a test of humanity's ability to build structures on other planets. This work focuses on simulating the response of small to large-scale radio arrays on the Moon consisting of hundreds or thousands of antennas. The response of the array is dependent on the structure of the emission along with the configuration and sensitivity of the array. A set of locations are selected for the simulated radio receivers, using Digital Elevation Models from the Lunar Orbiter Laser Altimeter instrument on Lunar Reconnaissance Orbiter to characterize the elevation of the receiver locations. A custom Common Astronomy Software Applications code is described and used to process the data from the simulated receivers, aligning the lunar and sky coordinate frames using SPICE to ensure the proper projections are used for imaging. This simulation framework is useful for iterating array design for imaging any given scientific target in a small field of view. This framework does not currently support all sky imaging.