Molecular dynamics of human alpha-fetoprotein fragment LDSYQCT and its analogs at different dielectric constants

A comparative study of the conformation dynamics of the human alpha-fetoprotein fragment LDSYQCT and heptapeptides derived from it by point substitutions has revealed a significant influence of electrostatic interactions on the set of preferred conformations and dynamics of amino acid residues when the peptides with blocked termini are examined at ? = 1. Peptide flexibility rises when the termini are left free (charged). At ? = 10 or 80, the set of probable conformations for all residues expands to much the same extent, i.e., at higher permittivity of the medium the dynamic effects of amino acid changes are leveled off.     

Evidence for a credit-card-swipe mechanism in the human PC floppase ABCB4

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A Refined Open State of the Glycine Receptor Obtained via Molecular Dynamics Simulations

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Lipid‐Embedded Molecular Dynamics Simulation Model for Exploring the Reverse Prostaglandin D2 Agonism of CT‐133 towards CRTH2 in the Treatment of Type‐2 Inflammation Dependent Diseases

Chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTH2) has been involved in several inflammation dependent diseases by mediating the chemotaxis of pro‐inflammatory cells in response to allergy and other responses through PGD2 ligation. This CRTH2‐PGD2 signaling pathway has become a target for treating allergic and type 2 inflammation dependent diseases, with many inhibitors developed to target the PGD2 binding pocket. One of such inhibitors is the ramatroban analog, CT‐133, which exhibited therapeutic potency cigarette smoke‐induced acute lung injury in patients. Nonetheless, the molecular mechanism and structural dynamics that accounts for its therapeutic prowess remain unclear. Employing computational tools, this study revealed that although the carboxylate moiety in CT‐133 and the native agonist PGD2 aided in their stability within the CRTH2 binding pocket, the tetrahydrocarbazole group of CT‐133 engaged in strong interactions with binding pocket residues which could have formed as the basis of the antagonistic advantage of CT‐133. Tetrahydrocarbazole group interactions also enhanced the relative stability CT‐133 within the binding pocket which consequently favored CT‐133 binding affinity. CT‐133 binding also induced an inactive or ‘desensitized’ state in the helix 8 of CRTH2 which could conversely favor the recruitment of arrestin. These revelations would aid in the speedy development of small molecule inhibitors of CRTH2 in the treatment of type 2 inflammation dependent diseases.     

Stable Li Metal Anode Enabled by Space Confinement and Uniform Curvature through Lithiophilic Nanotube Arrays

The application of lithium (Li) metal anodes in rechargeable batteries is primarily restricted by Li dendrite growth on the metal's surface, which leads to shortened cycle life and safety concerns. Herein, well‐spaced nanotubes with ultrauniform surface curvature are introduced as a Li metal anode structure. The ultrauniform nanotubular surface generates uniform local electric fields that evenly attract Li‐ions to the surface, thereby inducing even current density distribution. Moreover, the well‐defined nanotube spacing offers Li diffusion pathways to the electroactive areas as well as the confined spaces to host deposited Li. These structural attributes create a unique electrodeposition manner; i.e., Li metal homogenously deposits on the nanotubular wall, causing each Li nanotube to grow in circumference without obvious sign of dendritic formation. Thus, the full‐cell battery with the spaced Li nanotubes exhibits a high specific capacity of 132 mA h g^?1 at 1 C and an excellent coulombic efficiency of ≈99.85% over 400 cycles.     

Monte Carlo study on the secondary cancer risk estimations for patients undergoing prostate radiotherapy: A humanoid phantom study

AimThe aim of this study was to estimate the secondary malignancy risk from the radiation in FFB prostate linac-based radiotherapy for different organs of the patient.BackgroundRadiation therapy is one of the main procedures of cancer treatment. However, the application the radiation may impose dose to organs of the patient which can be the cause of some malignancies.Materials and methodsMonte Carlo (MC) simulation was used to calculate radiation doses to patient organs in 18 MV linear accelerator (linac) based radiotherapy. A humanoid MC phantom was used to calculate the equivalent dose s for different organs and probability of secondary cancer, fatal and nonfatal risk, and other risks and parameters related to megavoltage radiation therapy. In out-of-field radiation calculation, it could be seen that neutrons imparted a higher dose to distant organs, and the dose to surrounding organs was mainly due to absorbed scattered photons and electron contamination.ResultsOur results showed that the bladder and skin with 54.89 × 10⁻³ mSv/Gy and 46.09 × 10⁻³ mSv/Gy, respectively, absorbed the highest equivalent dose s from photoneutrons, while a lower dose was absorbed by the lung at 3.42 × 10⁻³ mSv/Gy. The large intestine and bladder absorbed 55.00 × 10⁻³ mSv/Gy and 49.08 × 10⁻³, respectively, which were the highest equivalent dose s due to photons. The brain absorbed the lowest out-of-field dose, at 1.87 × 10⁻³ mSv/Gy.ConclusionsWe concluded that secondary neutron portion was higher than other radiation. Then, we recommended more attention to neutrons in the radiation protection in linac based high energy radiotherapy.     

Assessment of skin dose in breast cancer radiotherapy: on-phantom measurement and Monte Carlo simulation

AimThe main purpose of the present study is assessment of skin dose in breast cancer radiotherapy.BackgroundAccurate assessment of skin dose in radiotherapy can provide useful information for clinical considerations.Materials and methodsA RANDO phantom was irradiated using a 6 MV Siemens Primus linac with medial and tangential radiotherapy fields for simulating breast cancer treatment. Dosimetry was also performed on various positions across the fields using an EBT3 radiochromic film. Similar conditions of measurement on the RANDO phantom including field size, irradiation angle, number of fields, etc. were subsequently simulated via the Monte Carlo N-Particle Transport code (MCNP). Ultimately, dose values for corresponding points from both methods were compared.ResultsConsidering dosimetry using radiochromic films on the RANDO phantom, there were points having underdose and overdose based on the prescribed dose and skin tolerance levels. In this respect, 81.25% and 18.75% of the points had underdose and overdose, respectively. In some cases, several differences were observed between the measurement and the MCNP simulation results associated with skin dose.ConclusionBased on the results of the points which had underdose, it was suggested that a bolus should be used for the given points. With regard to overdose points, it was advocated to consider skin tolerance dose in treatment planning. Differences between the measurement and the MCNP simulation results might be due to voxel size of tally cells in simulations, effect of beam’s angle of incidence, validation time of linac’s head, lack of electronic equilibrium in the build-up region, as well as MCNP tally type.     

Technoecological analysis of energy carriers for long‐haul transportation

Long‐haul transportation demand is predicted to increase in the future, resulting in higher carbon dioxide emissions. Different drivetrain technologies, such as hybrid or battery electric vehicles, electrified roads, liquefied natural gas and hydrogen, might offer solutions to this problem. To assess their ecological and economic impact, these concepts were simulated including a weight and cost model to estimate the total cost of ownership. An evolutionary algorithm optimizes each vehicle to find a concept specific optimal solution. A model calculates the minimum investment in infrastructure required to meet the energy demand for each concept. A well‐to‐wheel analysis takes into account upstream and on‐road carbon dioxide emissions, to compare fully electric vehicles with conventional combustion engines. Investment in new infrastructure is the biggest drawback of electrified road concepts, although they offer low CO₂ emissions. The diesel hybrid is the best compromise between carbon reduction and costs.