Phonological typicality influences sentence processing in predictive contexts: Reply to Staub, Grant, Clifton, and Rayner (2009).

In 2 separate self-paced reading experiments, Farmer, Christiansen, and Monaghan (2006) found that the degree to which a word's phonology is typical of other words in its lexical category influences online processing of nouns and verbs in predictive contexts. Staub, Grant, Clifton, and Rayner (2009) failed to find an effect of phonological typicality when they combined stimuli from the separate experiments into a single experiment. We replicated Staub et al.'s experiment and found that the combination of stimulus sets affects the predictiveness of the syntactic context; this reduces the phonological typicality effect as the experiment proceeds, although the phonological typicality effect was still evident early in the experiment. Although an ambiguous context may diminish sensitivity to the probabilistic relationship between the sound of a word and its lexical category, phonological typicality does influence online sentence processing during normal reading when the syntactic context is predictive of the lexical category of upcoming words. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Miconazole and Miconazolenitrate Chewing Gum as Drug Delivery Systems - A Practical Application of Solid Dispersion Technique

Miconazole and miconazolenitrate are antifungal drugs with poor solubilities in water and saliva. The low solubilities meant that only small amounts of the drugs-incorporated by a conventional method in chewing gum-were released during mastication. The experiments were performed on a mastication device.

In this study it was shown that application of a 20% miconazole - 80% polyethyleneglycol 6000 solid dispersion drastically improved the in vitro release of miconazole from cheving gum, when a medium similar to saliva was used. In addition to polyethyleneglycol 6000, polyvinylpyrrolidone 40000, xylitol and urea were tested as carriers. It was also shown that the release rate of miconazole from chewing gum was much greater than the release rate of miconazolenitrate.

No certain correlation could be shown between the dissolution rates of the solid dispersions measured by a stirring paddle method and the release rates of miconazole from solid dispersions in chewing gum.

The solid dispersion systems were characterized by differential scanning calorimetry. The systems containing polyethyleneglycol 6000 and xylitol were eutectic. Polyvinylpyrrolidone 40000 prevented crystallisation of miconazole when the percentage of drug in the solid dispersion was less than 50%.     

The total quasi-steady-state approximation for complex enzyme reactions

Biochemistry in general and enzyme kinetics in particular have been heavily influenced by the model of biochemical reactions known as Michaelis–Menten kinetics. Assuming that the complex concentration is approximately constant after a short transient phase leads to the usual Michaelis–Menten (MM) approximation (or standard quasi-steady-state approximation (sQSSA)), which is valid when the enzyme concentration is sufficiently small. This condition is usually fulfilled for in vitro experiments, but often breaks down in vivo. The total QSSA (tQSSA), which is valid for a broader range of parameters covering both high and low enzyme concentrations, has been introduced in the last two decades. We extend the tQSSA to more complex reaction schemes, like fully competitive reactions, double phosphorylation, Goldbeter–Koshland switch and we show that for a very large range of parameters our tQSSA provides excellent fitting to the solutions of the full system, better than the sQSSA and the single reaction tQSSA. Finally, we discuss the need for a correct model formulation when doing “reverse engineering”, which aims at finding unknown parameters by fitting the model to experimentally obtained data. We show that the estimated parameters are much closer to the real values when using the tQSSA rather than the sQSSA, which overestimates the parameter values greatly.     

Structural and electrical properties of perovskite ruthenate-based lead-free thick film resistors on alumina and LTCC

CaRuO₃ perovskite-based lead-free thick-film resistors (TFRs) were prepared on 96%-alumina and Low Temperature Co-fired Ceramic (LTCC) substrates. The microstructure evolution, possible interactions, and electrical properties of resistors were investigated. The hot and cold TCR values of all the resistors were measured in the temperature range (+20 to +120 ^∘C) and (+20 to −120 ^∘C), respectively. TFRs with 25% by vol. of CaRuO₃ on alumina exhibit a sheet resistance R_s = 5kΩ/sq. with hot and cold TCR of 225 and 470 ppm/^∘C respectively, whereas the same composition gives 1.2 kΩ/sq., 16.5 kΩ/sq. and 0.7 kΩ/sq. for co-fired, post-fired resistors on LTCC and buried resistors, respectively. The hot (HTCR) and cold (CTCR) values were evaluated; HTCR = 190 ppm/^∘C and CTCR = 314 ppm/^∘C were found for co-fired structures; HTCR = 216 ppm/^∘C and CTCR = 205 ppm/^∘C for post-fired samples and HTCR = 520 ppm/^∘C and CTCR = 350 ppm/^∘C for buried in LTCC structures.     

Near-infrared spectroscopy for cocrystal screening. A comparative study with Raman spectroscopy

Near-infrared (NIR) spectroscopy is a well-established technique for solid-state analysis, providing fast, noninvasive measurements. The use of NIR spectroscopy for polymorph screening and the associated advantages have recently been demonstrated. The objective of this work was to evaluate the analytical potential of NIR spectroscopy for cocrystal screening using Raman spectroscopy as a comparative method. Indomethacin was used as the parent molecule, while saccharin and l-aspartic acid were chosen as guest molecules. Molar ratios of 1:1 for each system were subjected to two types of preparative methods. In the case of saccharin, liquid-assisted cogrinding as well as cocrystallization from solution resulted in a stable 1:1 cocrystalline phase termed IND-SAC cocrystal. For l-aspartic acid, the solution-based method resulted in a polymorphic transition of indomethacin into the metastable alpha form retained in a physical mixture with the guest molecule, while liquid-assisted cogrinding did not induce any changes in the crystal lattice. The good chemical peak selectivity of Raman spectroscopy allowed a straightforward interpretation of sample data by analyzing peak positions and comparing to those of pure references. In addition, Raman spectroscopy provided additional information on the crystal structure of the IND-SAC cocrystal. The broad spectral line shapes of NIR spectra make visual interpretation of the spectra difficult, and consequently, multivariate modeling by principal component analysis (PCA) was applied. Successful use of NIR/PCA was possible only through the inclusion of a set of reference mixtures of parent and guest molecules representing possible solid-state outcomes from the cocrystal screening. The practical hurdle related to the need for reference mixtures seems to restrict the applicability of NIR spectroscopy in cocrystal screening.     

Conscious and anaesthetised Göttingen mini-pigs as an in-vivo model for buccal absorption – pH-dependent absorption of metoprolol from bioadhesive tablets

The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The T_max obtained from the two buccal conscious groups (55?±?5 and 35?±?5?min) were significantly different to the buccal anaesthetised groups (120?±?0 and 165?±?15?min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7?±?4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.     

Measurement of CH4-concentration in HMDSO-containing process plasmas by quantum cascade laser absorption spectroscopy

For thin film deposition or plasma etching often organic precursors are used in the process plasma and related transient species are formed. In general it is not possible to measure the converted quantity of these precursors directly. In the present work we have used a special laser absorption spectroscopy to investigate characteristic molecular lines in the plasma to determine the concentration of stable organic molecules. Quantum cascade laser absorption spectroscopy (QCLAS) is a rather new technique for the precise measurement of absolute molecule concentrations. QCL’s can be operated at room temperature. They emit light within the mid infrared and have similar spectroscopic characteristics to Tunable Diode Lasers (TDL). The commercially available system Q-MACS (Quantum Cascade Laser Measurement and Control System) offers a solid platform for the measurement of absolute molecule concentrations in plasmas and gas mixtures. The used Q-MACS is due to its laser characteristics particularly well suitable for determination of the concentrations of acetylene and methane. Molecular concentrations of methane were measured in hexamethyldisiloxane (HMDSO) containing plasmas, too. The methane concentration was found to depend on rf power and HMDSO flow.     

Suspension system performance optimization with discrete design variables

Suspension systems on commercial vehicles have become an important feature meeting the requirements from costumers and legislation. The performance of the suspension system is often limited by available catalogue components. Additionally the suspension performance is restricted by the travel speed which highly influences the ride comfort. In this article a suspension system for an articulated dump truck is optimized in sense of reducing elapsed time for two specified duty cycles without violating a certain comfort threshold level. The comfort threshold level is here defined as a whole-body vibration level calculated by ISO 2631-1. A three-dimensional multibody dynamics simulation model is applied to evaluate the suspension performance. A non-gradient optimization routine is used to find the best possible combination of continuous and discrete design variables including the optimum operational speed without violating a set of side constraints. The result shows that the comfort level converges to the comfort threshold level. Thus it is shown that the operational speed and hence the operator input influences the ride comfort level. Three catalogue components are identified by the optimization routine together with a set of continuous design variables and two operational speeds one for each load case. Thus the work demonstrates handling of human factors in optimization of a mechanical system with discrete and continuous design variables.     

Interactive topology optimization on hand-held devices

This paper presents an interactive topology optimization application designed for hand-held devices running iOS or Android. The TopOpt app solves the 2D minimum compliance problem with interactive control of load and support positions as well as volume fraction. Thus, it is possible to change the problem settings on the fly and watch the design evolve to a new optimum in real time. The use of an interactive app makes it extremely simple to learn and understand the influence of load-directions, support conditions and volume fraction. The topology optimization kernel is written in C# and the graphical user interface is developed using the game engine Unity3D. The underlying code is inspired by the publicly available 88 and 99 line Matlab codes for topology optimization but does not utilize any low-level linear algebra routines such as BLAS or LAPACK. The TopOpt App can be downloaded on iOS devices from the Apple App Store, at Google Play for the Android platform, and a web-version can be run from www.topopt.dtu.dk.     

Redesign of adaptive observers for improved parameter identification in nonlinear systems

We propose a method for redesigning adaptive observers for nonlinear systems. The redesign uses an adaptive law that is based on delayed observers. This increases the computational burden, but gives significantly better parameter identification and robustness properties. In particular, given that a special persistency of excitation condition is satisfied, we prove uniform global asymptotic stability and semi-global exponential stability of the origin of the state and parameter estimation error, and give explicit lower bounds on the convergence rate of both the state and parameter estimation error dynamics. For initial conditions with a known upper bound, we prove tunable exponential convergence rate. To illustrate the use of the proposed method, we apply it to estimate the unmeasured flow rate and the uncertain friction parameters in a model of a managed pressure drilling system. The simulation results clearly show the improved performance of the redesigned adaptive observer compared to a traditional design.