Development of a more accurate Geant4 quantum molecular dynamics model for hadron therapy.

Objective. Although in heavy-ion therapy, the quantum molecular dynamics (QMD) model is one of the most fundamental physics models providing an accurate daughter-ion production yield in the final state, there are still non-negligible differences with the experimental results. The aim of this study is to improve fragment production in water phantoms by developing a more accurate QMD model in Geant4.Approach. A QMD model was developed by implementing modern Skyrme interaction parameter sets, as well as by incorporating with an ad hocα-cluster model in the initial nuclear state. Two adjusting parameters were selected that can significantly affect the fragment productions in the QMD model: the radius to discriminate a cluster to which nucleons belong after the nucleus-nucleus reaction, denoted byR, and the squared standard deviation of the Gaussian packet, denoted byL. Squared Mahalanobis's distance of fragment yields and angular distributions with 1, 2, and the higher atomic number for the produced fragments were employed as objective functions, and multi-objective optimization (MOO), which make it possible to compare quantitatively the simulated production yields with the reference experimental data, was performed.Main results. The MOO analysis showed that the QMD model with modern Skyrme parameters coupled with the proposedα-cluster model, denoted as SkM*α, can drastically improve light fragments yields in water. In addition, the proposed model reproduced the kinetic energy distribution of the fragments accurately. The optimizedLin SkM*αwas confirmed to be realistic by the charge radii analysis in the ground state formation.Significance. The proposed framework using MOO was demonstrated to be very useful in judging the superiority of the proposed nuclear model. The optimized QMD model is expected to improve the accuracy of heavy-ion therapy dosimetry.

Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo.

The ability of gene transfer with the pore-forming subunit of the human maxi-K channel (hSlo) to ameliorate the decline in erectile capacity commensurate with 12-24 wk of streptozotocin (STZ)-diabetes was examined in 181 Fischer-344 rats. A 2-mo period of STZ-diabetes was induced before gene transfer, and erectile capacity was evaluated by measuring the intracavernous pressure response (ICP) to cavernous nerve (CN) stimulation (ranging from 0.5 to 10 mA). In the first series of experiments, ANOVA revealed increased CN-stimulated ICP responses at 1 and 2 mo postinjection of 100 microg pcDNA-hSlo compared with control values. A second series of experiments further examined the dose dependence and duration of gene transfer. The ICP response to submaximal (0.5 mA) and maximal (10 mA) nerve stimulation was evaluated 3 or 4 mo postinjection of a single dose of pcDNA-hSlo ranging from 10 to 1,000 microg. ANOVA again revealed that hSlo overexpression was associated with increased CN-stimulated ICP responses compared with responses in corresponding control animals. Histological studies revealed no immune response to the presence of hSlo. PCR analysis documented that expression of both plasmid and transcript were largely confined to the corporal tissue. In the third series of pharmacological experiments, hSlo gene transfer in vivo was associated with iberiotoxin-sensitive relaxation responses to sodium nitroprusside in corporal tissue strips in vitro. The latter data indicate that gene transfer produces functional maxi-K channels that participate in the modulation of corporal smooth muscle cell tone. Taken together, these observations suggest a fundamental diabetes-related change in corporal myocyte maxi-K channel regulation, expression, or function that may be corrected by expression of recombinant hSlo.