A microdosimetry application for Microbeam Radiation Therapy dose delivery using TOPAS

Microbeam Radiation Therapy as a cancer treatment is developing fast due to its high therapeutic effect. This work simulates the MRT setup and the multi-slit collimator used in the creation of microbeams with the aid of TOPAS. TOPAS is a Geant4-based Monte Carlo extension developed to make simulations more readily available to both research and clinical medical physicists, as well as to extend its functionality. A multi-slit collimator is modelled to produce x-ray microbeams with a width of 50 μm and a centre to centre spacing of 400 μm. The energies range from 0 to 600 keV, and they are sampled using the synchrotron-wiggler generated spectrum employed at the biomedical facility of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. This work aims to identify the accuracy of the dose deposition curves and peak to valley dose ratios (PVDRs) obtained with TOPAS. The PVDRs decreased with depth but increased prior to phantom exit due to the absence of back scattering. The simulated results are in line with published simulated and empirical findings, which suggest that TOPAS can be satisfactorily used as a tool for the calculation of the percentage depth dose and PVDRs at the energies considered in this study

Loss of tubulin deglutamylase CCP1 causes infantile-onset neurodegeneration.

A set of glutamylases and deglutamylases controls levels of tubulin polyglutamylation, a prominent post-translational modification of neuronal microtubules. Defective tubulin polyglutamylation was first linked to neurodegeneration in the Purkinje cell degeneration (pcd) mouse, which lacks deglutamylase CCP1, displays massive cerebellar atrophy, and accumulates abnormally glutamylated tubulin in degenerating neurons. We found biallelic rare and damaging variants in the gene encoding CCP1 in 13 individuals with infantile-onset neurodegeneration and confirmed the absence of functional CCP1 along with dysregulated tubulin polyglutamylation. The human disease mainly affected the cerebellum, spinal motor neurons, and peripheral nerves. We also demonstrate previously unrecognized peripheral nerve and spinal motor neuron degeneration in pcd mice, which thus recapitulated key features of the human disease. Our findings link human neurodegeneration to tubulin polyglutamylation, entailing this post-translational modification as a potential target for drug development for neurodegenerative disorders

Demonstration of ignition radiation temperatures in indirect-drive inertial confinement fusion hohlraums

We demonstrate the hohlraum radiation temperature and symmetry required for ignition-scale inertial confinement fusion capsule implosions. Cryogenic gas-filled hohlraums with 2.2 mm-diameter capsules are heated with unprecedented laser energies of 1.2 MJ delivered by 192 ultraviolet laser beams on the National Ignition Facility. Laser backscatter measurements show that these hohlraums absorb 87% to 91% of the incident laser power resulting in peak radiation temperatures of TRAD=300  eV and a symmetric implosion to a 100  μm diameter hot core