In vitro studies of PDR brachytherapy

BACKGROUND: Calculations on the basis of the LQ-model have been focussed on the possible radiobiological equivalence between common continuous low dose rate irradiation (CLDR) and a superfractionated irradiation (PDR = pulsed dose rate) provided that the same total dose will be prescribed in the same overall time as with the low doserate. A clinically usable fractionation scheme for brachytherapy was recommended by Brenner and Hall and should replace the classical CLDR brachytherapy with line sources with an afterloading technique using a stepping source. The hypothes is that LDR equivalency can be achieved by superfractionation was tested by means of in vitro experiments on V79 cells in monolayer and spheroid cultures as well as on HeLa monolayers. MATERIALS AND METHODS: Simulating the clinical situation in PDR brachytherapy, fractionation experiments were carried out in the dose rate gradient of afterloading sources. Different dose levels were produced with the same number of fractions in the same overall incubation time. The fractionation schedules which were to be compared with a CLDR reference curve were: 40 x 0.47 Gy, 20 x 0.94 Gy, 10 x 1.88 Gy, 5 x 3.76 Gy, 2 x 9.4 Gy given in a period of 20 h and 1 x 18.8 Gy as a "single dose" exposition. As measured by flow cytometry, the influence of the dose rate in the pulse on cell survival and on cell cycle distribution under superfractionation was examined on V79 cells. RESULTS: V79 spheroids as a model for a slowly growing tumor, reacted according to the radiobiological calculations, as a CLDR equivalency was achieved with increasing fractionation. Rapidly growing V79 monolayer cells showed an inverse fractionation effect. A superfractionated irradiation with pulses of 0.94 Gy/h respectively 0.47 Gy/0.5 h was significantly more effective than the CLDR irradiation. This inverse fractionation effect in log-phase V79 cells could be attributed to the accumulation of cycling cells in the radiosensitive G2/M phase (G2 block) during protected exposure which was drastically more pronounced for the pulsed scheme. HeLa cells were rather insensitive to changes of fractionation. Superfractionation as well as hypofractionation yielded CLDR equivalent survival curves. CONCLUSIONS: The fractionation scheme, derived from the PDR theory to achieve CLDR equivalent effects, is valid for many cell lines, however not for all. Proliferation and dose rate dependend cell cycle effects modify predictions derived from the sublethal damage recovery model and can influence acute irradiation effects significantly. Dose rate sensitivity and rapid proliferation favour cell cycle effects and substantiate, applied to the clinical situation, the possibility of a higher effectiveness of the pulsed irradiation on rapidly growing tumors.     

Combination of fiber-guided pulsed erbium and holmium laser radiation for tissue ablation under water

Because of the high absorption of near-infrared laser radiation in biological tissue, erbium lasers and holmium lasers emitting at 3 and 2 μm, respectively, have been proven to have optimal qualities for cutting or welding and coagulating tissue. To combine the advantages of both wavelengths, we realized a multiwavelength laser system by simultaneously guiding erbium and holmium laser radiation by means of a single zirconium fluoride (ZrF(4)) fiber. Laser-induced channel formation in water and poly(acrylamide) gel was investigated by the use of a time-resolved flash-photography setup, while pressure transients were recorded simultaneously with a needle hydrophone. The shapes and depths of vapor channels produced in water and in a submerged gel after single erbium and after combination erbium-holmium radiation delivered by means of a 400-μm ZrF(4) fiber were measured. Transmission measurements were performed to determine the amount of pulse energy available for tissue ablation. The effects of laser wavelength and the delay time between pulses of different wavelengths on the photomechanical and photothermal responses of meniscal tissue were evaluated in vitro by the use of histology. It was observed that the use of a short (200-μs, 100-mJ) holmium laser pulse as a prepulse to generate a vapor bubble through which the ablating erbium laser pulse can be transmitted (delay time, 100 μs) increases the cutting depth in meniscus from 450 to 1120 μm as compared with the depth following a single erbium pulse. The results indicate that a combination of erbium and holmium laser radiation precisely and efficiently cuts tissue under water with 20-50-μm collateral tissue damage.     

Structural and residual stress changes in Mo/a-Si multilayer thin films with annealing

The thermal and mechanical stability of molybdenum and amorphous silicon (Mo/a-Si) optical multilayers (3 and 4 nm nominal thickness of Mo and Si) at 316 °C were studied by annealing experiments. Growth of amorphous Mo-Si interlayers with a stoichiometry of 12 was observed at the Mo/a-Si interfaces. In addition, residual stresses significantly changed in the crystalline Mo and amorphous Si layers with annealing. High resolution electron microscopy, selected area electron diffraction, and X-ray diffraction of the crystalline Mo revealed that tensile stresses increased from 2 to about 10 GPa in the lateral direction (parallel to the interface plane). The compressive strains that developed in the vertical direction (perpendicular to the interface plane) are consistent with Poisson's ratio. Laser deflectometer measurements of thicker (0.1 m) amorphous silicon layers may indicate compressive-stress relaxation in the amorphous silicon with annealing, consistent with other investigations. Overall, the residual stress in a 40-bilayer film changes from about –0.5 to about +1.5 GPa. Structural transformation after relatively short annealing times at the interfaces in the thin amorphous Mo-Si interlayers may rationalize increased tensile strains in the Mo layers.     

Nutritional regulation of the activities of lipogenic enzymes of rat liver and brown adipose tissue

Nutrition-induced effects on the activity of enzymes of lipogenesis, fatty acid synthase (FAS: EC 2.3.1.85), ATP citrate lyase (ACL: EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH: EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44) were investigated in liver and interscapular brown adipose tissue (BAT) of rats. The lipogenic enzymes could be grouped into two categories according to their response to dietary manipulations: FAS and ACL, both key enzymes of lipogenesis, responded fast and strongly to dietary manipulations. ME, G6PDH and PGDH, enzymes which also contribute to metabolic pathways other than lipogenesis, responded in a more sustained and less pronounced fashion. Feed deprivation caused the specific activities of lipogenic enzymes to decline several-fold. Refeeding of previously fasted (up to 3 days) animals increased the activities dramatically (10-to 25-fold) to far above pre-fasting levels ("overshoot"). Repetition of the fasting/refeeding regimen increasingly impaired the ability of both tissues to synthesize overshooting enzyme activities in the subsequent refeeding period. The fasting-induced decline of the activities was prevented when sugars were provided to the animals via drinking water. The sugars displayed different effectivities: sucrose = glucose > fructose > maltose > > lactose. Sugars as the sole nutrient after fasting were also able to induce overshooting enzyme activities. Again, activities of FAS and ACL responded in a more pronounced fashion than the other three enzymes. Transition from feeding one diet to feeding a new diet of different composition led to adaptation of the lipogenic enzyme activities to levels characteristic for the new diet. Replacing a low-carbohydrate with a high-carbohydrate diet proceeded with major alterations of enzyme activities. This process of attaining a new level took up to 20 days and involved pronounced oscillations of the specific activities. In contrast, when a high-carbohydrate diet was replaced with another diet. particular one high in fat, transition to new enzyme activities was completed within 2-3 days and proceeded without oscillations. All dietary manipulations caused more pronounced responses in young (35d-old) than in adult (180d-old) animals.     

Beyond loop bounds: comparing annotation languages for worst-case execution time analysis

Worst-case execution time (WCET) analysis is concerned with computing a precise-as-possible bound for the maximum time the execution of a program can take. This information is indispensable for developing safety-critical real-time systems, e. g., in the avionics and automotive fields. Starting with the initial works of Chen, Mok, Puschner, Shaw, and others in the mid and late 1980s, WCET analysis turned into a well-established and vibrant field of research and development in academia and industry. The increasing number and diversity of hardware and software platforms and the ongoing rapid technological advancement became drivers for the development of a wide array of distinct methods and tools for WCET analysis. The precision, generality, and efficiency of these methods and tools depend much on the expressiveness and usability of the annotation languages that are used to describe feasible and infeasible program paths. In this article we survey the annotation languages which we consider formative for the field. By investigating and comparing their individual strengths and limitations with respect to a set of pivotal criteria, we provide a coherent overview of the state of the art. Identifying open issues, we encourage further research. This way, our approach is orthogonal and complementary to a recent approach of Wilhelm et al. who provide a thorough survey of WCET analysis methods and tools that have been developed and used in academia and industry.     

A modified design approach for compact ultra‐wideband microstrip filters

A modified design approach for compact ultra‐wideband microstrip filters with cascaded/folded stepped‐impedance resonators is described. The key feature of the proposed method is to facilitate stronger coupling between stepped‐impedance resonators and, at the same time, eliminate the requirement of extremely small gaps in coupled‐line sections, as found in traditional designs. Simulations and measurements demonstrate that the filters designed with this technique exhibit good reflection, insertion‐loss, and group‐delay performance within the 3.1–10.6 GHz band. © 2009 Wiley Periodicals, Inc. Int J RF and Microwave CAE 2010.     

Liquid recirculation in microfluidic channels by the interplay of capillary and centrifugal forces

We demonstrate a technique to recirculate liquids in a microfluidic channel by alternating predominance of centrifugal and capillary forces to rapidly bring the entire volume of a liquid sample to within one diffusion length, δ, of the surface, even for sample volumes hundreds of times the product of δ and the geometric device area. This is accomplished by repetitive, random sampling of an on-disc sample reservoir to form a thin fluid layer of thickness δ in a microchannel, maintaining contact for the diffusion time, then rapidly exchanging the fluid layer for a fresh aliquot by disc rotation and stoppage. With this technique, liquid volumes of microlitres to millilitres can be handled in many sizes of microfluidic channels, provided the channel wall with greatest surface area is hydrophilic. We present a theoretical model describing the balance of centrifugal and capillary forces in the device and validate the model experimentally.     

Adaptive Finite Element Simulation of the Time-dependent Simplified <Emphasis Type="Italic">P</Emphasis><Subscript><Emphasis Type="Italic">N</Emphasis></Subscript> Equations

The steady-state simplified P _N approximation to the radiative transfer equation has been successfully applied to many problems involving radiation. Recently, time-dependent simplified P _N equations have been derived by an asymptotic analysis similar to the asymptotic derivation of the steady-state SP _N equations (Frank et al. in J. Comput. Phys. 226:2289–2305, 2007). In this paper, we present computational results for the time-dependent SP _N equations in two dimensions, obtained by using an adaptive finite element approach. Several numerical comparisons with other existing models are shown.     

The Covering Law Model Applied to Dynamical Cognitive Science: A Comment on Joel Walmsley

In a 2008 paper, Walmsley argued that the explanations employed in the dynamical approach to cognitive science, as exemplified by the Haken, Kelso and Bunz model of rhythmic finger movement, and the model of infant preservative reaching developed by Esther Thelen and her colleagues, conform to Carl Hempel and Paul Oppenheim’s deductive-nomological model of explanation (also known as the covering law model). Although we think Walmsley’s approach is methodologically sound in that it starts with an analysis of scientific practice rather than a general philosophical framework, we nevertheless feel that there are two problems with his paper. First, he focuses only on the deductivenomological model and so neglects the important fact that explanations are causal. Second, the explanations offered by the dynamical approach do not take the deductive-nomological format, because they do not deduce the explananda from exceptionless laws. Because of these two points, Walmsley makes the dynamical explanations in cognitive science appear problematic, while in fact they are not.