Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding.

The intrinsically disordered human protein alpha-Synuclein (αS) has a prominent role in Parkinson's disease (PD) pathology. Several familial variants of αS are correlated with inherited PD. Disease mutations have been shown to have an impact on lipid membrane binding. Here, using electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling, we show that familial PD-associated variants are structurally defective in membrane binding and alter the local binding properties of the protein.

Towards real-time EPID-based 3D in vivo dosimetry for IMRT with Deep Neural Networks: A feasibility study.

We investigate the potential of the Deep Dose Estimate (DDE) neural network to predict 3D dose distributions inside patients with Monte Carlo (MC) accuracy, based on transmitted EPID signals and patient CTs. The network was trained using as input patient CTs and first-order dose approximations (FOD). Accurate dose distributions (ADD) simulated with MC were given as training targets. 83 pelvic CTs were used to simulate ADDs and respective EPID signals for subfields of prostate IMRT plans (gantry at 0∘). FODs were produced as backprojections from the EPID signals. 581 ADD-FOD sets were produced and divided into training and test sets. An additional dataset simulated with gantry at 90∘ (lateral set) was used for evaluating the performance of the DDE at different beam directions. The quality of the FODs and DDE-predicted dose distributions (DDEP) with respect to ADDs, from the test and lateral sets, was evaluated with gamma analysis (3%,2 mm). The passing rates between FODs and ADDs were as low as 46%, while for DDEPs the passing rates were above 97% for the test set. Meaningful improvements were also observed for the lateral set. The high passing rates for DDEPs indicate that the DDE is able to convert FODs into ADDs. Moreover, the trained DDE predicts the dose inside a patient CT within 0.6 s/subfield (GPU), in contrast to 14 h needed for MC (CPU-cluster). 3D in vivo dose distributions due to clinical patient irradiation can be obtained within seconds, with MC-like accuracy, potentially paving the way towards real-time EPID-based in vivo dosimetry.

Optimization of Phase Space files from clinical linear accelerators.

This work proposes a methodology to produce an optimized phase-space (PhSp) for the Elekta Synergy linac by tuning the energy and direction of particles inside the 6-MV Elekta Precise PhSp, provided by the International Atomic Energy Agency (IAEA), for Monte Carlo (MC) simulations. First, the energies of the particles emerging from the original PhSp were increased by different factors, producing new PhSps. Percentage depth dose (PDD) profiles were simulated and compared to measured data from a Synergy linac for 6-MV photon beam. This process was repeated until a minimum difference was reached. Particles' directions were then manipulated following identified correlations to lateral profiles, resulting in two distinct perturbation factors based on inline and crossline profiles. Both factors were merged into one single optimal factor. For energy optimization, an increase of 0.32 MeV applied to all particles inside the original PhSp, but to 0.511 MeV annihilation photons, provided the best results. The direction optimization factor was the combination of the individual factors for inline (0.605%) and crossline (0.051%). The agreement between measured and simulated profiles, when using the optimized PhSp, improved considerably in comparison to simulations performed with the original IAEA PhSp. For all fields and depths analyzed, the discrepancies for PDD, inline and crossline profiles dropped from 11.2%, 15.7% and 27.5% to under 1.4%, 4.7% and 13.2%, respectively. The optimized PhSp should not replace the full linac modelling, however it offers an alternative for MC dose calculations when neither geometric details nor validated IAEA PhSp are available to the user.

Phlebotomine sand fly fauna and leishmania infection in the vicinity of the Serra do Cipó National Park, a natural Brazilian heritage site.

In the New World, the leishmaniases are primarily transmitted to humans through the bites of Leishmania-infected Lutzomyia (Diptera: Psychodidae) phlebotomine sand flies. Any or both of two basic clinical forms of these diseases are endemic to several cities in Brazil--the American cutaneous leishmaniasis (ACL) and the American visceral leishmaniasis (AVL). The present study was conducted in the urban area of a small-sized Brazilian municipality (Jaboticatubas), in which three cases of AVL and nine of ACL have been reported in the last five years. Jaboticatubas is an important tourism hub, as it includes a major part of the Serra do Cipó National Park. Currently, no local data is available on the entomological fauna or circulating Leishmania. During the one-year period of this study, we captured 3,104 phlebotomine sand flies belonging to sixteen Lutzomyia species. In addition to identifying incriminated or suspected vectors of ACL with DNA of the etiological agent of AVL and vice versa, we also detected Leishmania DNA in unexpected Lutzomyia species. The expressive presence of vectors and natural Leishmania infection indicates favorable conditions for the spreading of leishmaniases in the vicinity of the Serra do Cipó National Park.