Scintillation detectors constructed with an optimized 2x2 silicon photomultiplier array

Silicon photomultipliers (SiPMs) are a good alternative to photomultiplier tubes (PMTs) because their gain and quantum efficiency are comparable to PMTs. However, the largest single-chip SiPM is still less than 1~cm$^2$. In order to use SiPMs with scintillators that have reasonable sensitivity, it is necessary to use multiple SiPMs. In this work, scintillation detectors are constructed and tested with a custom 2x2 SiPM array. The layout of the SiPMs and the geometry of the scintillator were determined by performing Geant4 simulations. Cubic NaI, CsI, and CLYC with 18~mm sides have been tested. The output of the scintillation detectors are stabilized over the temperature range between --20 and 50~$^{\circ}$C by matching the gain of the SiPMs in the array. The energy resolution for these detectors has been measured as a function of temperature. Furthermore, neutron detection for the CLYC detector was studied in the same temperature range. Using pulse-shape discrimination, neutrons can be cleanly identified without contribution from $\gamma$-photons. As a result, these detectors are suitable for deploying in spectroscopic personal radiation detectors (SPRD).Comment: IEEE Nuclear Science Symposium Conference Record (2016

Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase

Inhibition of monopolar spindle 1 MPS1 kinase represents a novel approach to cancer treatment instead of arresting the cell cycle in tumor cells, cells are driven into mitosis irrespective of DNA damage and unattached misattached chromosomes, resulting in aneuploidy and cell death. Starting points for our optimization efforts with the goal to identify MPS1 inhibitors were two HTS hits from the distinct chemical series triazolopyridines and imidazopyrazines . The major initial issue of the triazolopyridine series was the moderate potency of the HTS hits. The imidazopyrazine series displayed more than 10 fold higher potencies; however, in the early project phase, this series suffered from poor metabolic stability. Here, we outline the evolution of the two hit series to clinical candidates BAY 1161909 and BAY 1217389 and reveal how both clinical candidates bind to the ATP site of MPS1 kinase, while addressing different pockets utilizing different binding interactions, along with their synthesis and preclinical characterization in selected in vivo efficacy model