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.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

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.     

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.     

Kinetic Monte-Carlo simulation of network formation

Summary the simulation described in Part I was applied to random step polyaddition of a trifunctional monomer and the results were compared with exact solution for an infinite system. The gel point conversions, the weight-average degree of polymerization before (P _w) and beyond (P _w,sol) the gel point, the sol fraction and the cycle rank were used for comparison. The best way for detection of the gel point conversion is the extrapolation of the gel fraction, w _g, to w _g=0. The largest fluctuations are exhibited by P _w and P _w,sol. To get results closer to the exact ones, one can repeat several experiments with smaller number of units or increase the number of units, the former way being somewhat more economical. Typical orders of magnitude used were 10⁷ monomeric units.     

Depression in college students: Personality and experiential factors.

In this study we examined the nature of college-student depression and its relation to personality variables and to experiences unique to college life. Thirty-five depressed and 39 nondepressed students completed a depression inventory, a series of personality scales, and a survey developed to investigate the impact of potentially distressing components of college life. Results revealed that college-student depression, though mild in intensity, represents a serious problem: Three quarters of depressed students had been depressed for more than 3 months, and half had contemplated suicide. Both personality characteristics and experiential variables were found to be significantly related to depression, together accounting for approximately half the variance. We examined individual personality traits and experiential variables that were found to differ between depressed and nondepressed subjects, and we discuss the implications of the findings for counseling and for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low strain rate plasticity of continuously cast carbon steels

By a special plastometric method, the straightening operation of a vertically cast strand of two carbon steels was simulated. The temperature dependence of the low strain rate plasticity of both the steels examined is analogous although caused by very different reasons. As to the plain carbon steel, the amount of ferrite and its location is of prime importance, whereas in the case of eutectoid steel various modes of fracture and the influence of temperature on the relative plasticity of type II MnS inclusions are influencial. To avoid transverse cracking, it seems to be suitable to keep the strand at a rather high temperature (above 900 °C). Temperature cycling seems to be fundamental as to the structural changes taking place in the strand (grain size refining, ferrite fraction if any), whereas analogous influences of straining are more or less inexpressive. Of course, the results obtained are of quality only since the practical and laboratory conditions differ significantly. The knowledge obtained could be applied in regulating the intensity of strand cooling with the aim of lowering the waste portion and improving the surface quality of worked products.