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Mohammad Reza Dayer, Nooshin Azari, Nematollah Razmi, Mohammad Saeid Dayer,
Volume 17, Issue 7 (10-2014)
Abstract

Background: Prion diseases are neurodegenerative disorders which ultimately results in the death of their victims. They are caused by structural transformation of cellular prion (PrPC) to its &beta-rich and anomalous isoform (PrPSc) and the accumulation of amyloid fibrillar deposits in the central nervous system. The precise mechanism underling this conversion is yet to be well understood. This study aimed to investigate the effect of non physiological temperatures on the misfolding mechanism of the human prion protein.

Materials and Methods: The crystal structure of human prion protein (90-231), (PDB code: 2Lej) in pdb format was used as a starting structure in this study. Three model structures of this coordinate structure were used separately to simulate PrPC at 27 , 37 and 47 . Molecular dynamic simulations were then performed using double-precision MPI version of GROMACS 4.5.5 for 10 ns and the results were analyzed using SPSS software, SPDBV and VebLab programs.

Results: The change of temperature from 37 to 27 or 47 induced significant structural changes to PrPC. These tempratures caused PrPC to attain a more folded and less flexible tertiary structure compared to its native structure at 37 . They, also, reduce protein-solvent hydrogen bonds and therefore increasing access of hydrophobic solvent to PrPC which may be behind the lower water solubility of PrPC and its increased resistance to proteolytic degradations.

Conclusion: This study shows that changes of temperatures accelerate structural changes of PrPC and reduce its solubility while rendering it vulnerable to transition into PrPSc.


Zahra Ahmadi Ganjeh, Mohammad Eslami-Kalantari, Ali Asghar Mowlavi,
Volume 22, Issue 6 (1-2020)
Abstract

Background and Aim: Sicne in many dosimetry calculations, the water and soft tissue phantoms are used, this study aimed to investigate the difference of these two phantoms with a phantom consisted of realistic liver materials in proton therapy for liver cancer.
Methods & Materials: Three phantoms with different materials of water, soft tissue and realistic liver materials were used for the study. A spherical tumor with 2 cm radius was considered in the liver. The Spread-out Bragg Peaks (SOBPs) were measured to cover the complete tumor for the three phantoms. Dose distribution and deposited dose ratio in tumor and surrounding organs were calculated using Monte Carlo N-Particle Extended (MCNPX) code. 
Ethical Considerations: The best proton energy interval to complete the coverage of tumor in the liver for phantoms with realistic and soft tissue materials was 90-120 MeV and for water phantom, it was 88-116 MeV. The shift of the Bragg peaks depth per energy in the water phantom mm relative to two other phantoms was about 4.5. The dose parameters were evaluated according to the International Commission on Radiation Units and Measurements (ICRU), and the results showed no any significant difference between them. The dose distribution in the tumor and surrounding organs showed that for all three phantoms, the dose distribution around the tumor was negligible.
Results: The use of soft tissue phantom has more acceptable results than water phantom in simulating treatment and can be replaced with realistic liver tissue. More realistic phantoms should be used in treatment plan. 
Conclusion: The use of soft tissue phantom has more acceptable results than water phantom in simulating treatment and can be replaced with realistic liver tissue. More realistic phantoms should be used in treatment plan. 



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