An automated treatment planning strategy for highly noncoplanar radiotherapy arc trajectories

Radiation therapy is a technology-driven cancer treatment modality that has experienced significant advances over the last decades, due to multidisciplinary contributions that include engineering and computing. Recent technological developments allow the use of noncoplanar volumetric modulated arc therapy (VMAT), one of the most recent photon treatment techniques, in clinical practice. In this work, an automated noncoplanar arc trajectory optimization framework designed in two modular phases is presented. First, a noncoplanar beam angle optimization algorithm is used to obtain a set of noncoplanar irradiation directions. Then, anchored in these directions, an optimization strategy is proposed to compute an optimal arc trajectory. The computational experiments considered a pool of twelve difficult head-and-neck tumor cases. It was possible to observe that, for some of these cases, the optimized noncoplanar arc trajectories led to significant treatment planning quality improvements, when compared with coplanar VMAT treatment plans. Although these experiments were done in a research environment treatment planning software (matRad), the conclusions can be of interest for a clinical setting: automated procedures can simplify the current treatment workflow, produce high-quality treatment plans, making better use of human resources and allowing for unbiased comparisons between different treatment techniques.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Numerical analysis of Augmented Lagrangian algorithms in complementary elastoplasticity

The main subject of the paper is the investigation of Augmented Lagrangian algorithms and update formulas in the solution of elastoplastic problems. A stress rate formulation for elastoplastic models with internal variables and its finite increment form is employed to state the mechanical problem. In this formulation the Augmented Lagrangian is used to enforce the constraint of plastic admissibility directly on the stresses and thermodynamic forces. This is not a limitation of the Augmented Lagrangian approach, and the same framework can be built on more classical displacement formulations as well. The meaning and the derivation of various first and second order Lagrangian multipliers update formulas and iterative schemes is shown. A new diagonal iteration algorithm and the introduction of a scale factor for the Augmented Lagrangian term are proposed. Numerical examples compare the efficiency of several forms of Augmented Lagrangian algorithms and illustrate the influence of the scale factor and of the penalty parameter. Copyright © 2004 John Wiley & Sons, Ltd.     

Viscoelastic response of solid rocket motor components for service life assessment

A methodology for determining the response of rocket motor materials and bondlines to thermal loadings by measuring their dynamic mechanical properties is reported. The critical temperatures at which debonding and/or propellant cracking occur and the number of thermal cycles required to induce failure were evaluated. These results were compared with those from instrumented rocket motors subjected to similar thermal loadings. A model, developed for fibre reinforced composites, was applied to the propellant-inhibitor bimaterial obtained from a rocket motor. The internal energy dissipation due to a lack of perfect adhesion at the propellant–inhibitor interface, tan δ_adh, was used to give an indication of the failure mode of the bondline (i.e., adhesive failure at the interface or cohesive failure in the propellant) and the bond adhesion parameter, C, was related to the bond strength measured by rectangular bond-in-tension tests. This revised version was published online in November 2006 with corrections to the Cover Date.     

Has risk associated with smoking increased? Results from the Copenhagen Center for Prospective Population Studies

BACKGROUND: Two recent much cited publications have raised the concern that risk associated with cigarette smoking has so far been underestimated. In this study we wish to determine whether excess all-cause mortality associated with smoking has increased during the last 20-30 years in a study population representative of the general Danish population and whether any such changes relate to changes in smoking behaviour. METHODS: Pooled data from three prospective population studies conducted in Copenhagen with detailed information on smoking habits. A total of 31,194 subjects, 17,669 males and 13,525 females, initially examined between 1964 and 1992 with examinations repeated at intervals from 1-10 years, were followed until 1995 for all-cause mortality. Relative mortality risk in smokers versus never-smokers was calculated within periods of five calendar years and compared throughout the study period. RESULTS: Male smokers' exposure did not change during the study period whereas female smokers' exposure to tobacco increased in terms of age at smoking onset, quantity smoked and depth of inhalation. During follow-up 5744 males and 2900 females died. In males, death rate ratios (comparing continuous smokers with never-smokers) did not change in the study period. In females, ratios increased from 1964-1978 to 1979-1994 by a factor of 1.3 (95% confidence interval 1.0-1.8). CONCLUSIONS: In agreement with the observed changes in smoking habits, excess mortality in male smokers did not increase whereas excess mortality in female smokers increased slightly.     

A SURVEY OF ARYLAMINE N-ACETYLTRANSFERASE ACTIVITY IN COMMON FRUITS AND VEGETABLES

The N-acetyltransferase activity was determined in 58 common fruits and vegetables. The assay was based on acetylation of 2-aminofluorene or p-amino-benzoic acid, followed by high pressure liquid chromatographic analysis of products and remaining nonacetylated substrate. The highest specific activities were observed in Balsam pear which contained 17.37 ± 1.45 N-acetyl aminofluorene nmole/min/mg protein and 46.27 ± 6.87 N-acetyl p-aminobenzoic acid nmole/min/mg protein. N-acetyltransferase activities within the remaining 57 foodstuffs analyzed ranged from none detected to 3.39 ± 0.72 N-acetyl aminofluorene nmole/min/mg protein and none detected to 32.45 ± 6.55 N-acetyl p-aminobenzoic acid nmole/min/mg protein. This is the first demonstration of acetyl CoA: arylamine N-acetyltransferase activity in common foodstuffs.     

Evaluation of Textile Bobbins Drying Processes: Experimental and Modelling Studies

Drying of textile bobbins was carried out on two kinds of laboratory-scale dryers: in a cross circulation drying rig, atmospheric pressure heating air is used, while in the through circulation drying apparatus, the heating air is pressurized before the drying process takes place. In both cases, a bobbin was fitted with seven thermocouples, placed in a plane normal to the bobbin axis but at different radial distances, in order to provide temperature data during the drying process. In cross circulation drying, plots of temperature against time indicated the presence of two moving fronts, one starting from inside the bobbin, another from the outside, while in through circulation drying, similar plots showed the presence of an evaporation front, moving from inside the bobbin to the outside. In both canes, numerical models were developed to simulate the drying processes.     

Current concepts in dentin bonding: focusing on dentinal adhesion factors

With greater need for treating root surface lesions, dentinal adhesives are more in demand. For successful treatment, all factors--dentin, tooth, patient and materials--must be considered.