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Model Leads (model + lead)
Selected AbstractsLipophilic cationic drugs increase the permeability of lysosomal membranes in a cell culture system,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Johannes Kornhuber Lysosomes accumulate many drugs several fold higher compared to their extracellular concentration. This mechanism is believed to be responsible for many pharmacological effects. So far, uptake and release kinetics are largely unknown and interactions between concomitantly administered drugs often provoke mutual interference. In this study, we addressed these questions in a cell culture model. The molecular mechanism for lysosomal uptake kinetics was analyzed by live cell fluorescence microscopy in SY5Y cells using four drugs (amantadine, amitriptyline, cinnarizine, flavoxate) with different physicochemical properties. Drugs with higher lipophilicity accumulated more extensively within lysosomes, whereas a higher pKa value was associated with a more rapid uptake. The drug-induced displacement of LysoTracker was neither caused by elevation of intra-lysosomal pH, nor by increased lysosomal volume. We extended our previously developed numerical single cell model by introducing a dynamic feedback mechanism. The empirical data were in good agreement with the results obtained from the numerical model. The experimental data and results from the numerical model lead to the conclusion that intra-lysosomal accumulation of lipophilic xenobiotics enhances lysosomal membrane permeability. Manipulation of lysosomal membrane permeability might be useful to overcome, for example, multi-drug resistance by altering subcellular drug distribution. J. Cell. Physiol. 224:152,164, 2010 © 2010 Wiley-Liss, Inc. [source] Theoretical analysis of the effects of viscous losses and abdominal straining on urinary outlet function,NEUROUROLOGY AND URODYNAMICS, Issue 1 2004Srboljub M. Mijailovich Abstract Aims The aim of this study was to theoretically explore the relationship between the tube law (TL) of the urethra and the pressure,flow (p,Q) relationship during micturition. The understanding of this relation is important for the evaluation of outlet obstruction by urodynamic interpretation of p,Q plots. Methods We simulated the outlet function by a lumped theoretical model, and suggested how the TL can be used to quantitatively predict the p,Q relationship of the system. Our analysis considered the relation between the TL and the steady state p,Q plot for various TLs including the hysteresis of the pressure,area relationship. Results and Conclusions The inclusion of pressure losses distal to the flow controlling zone and experimentally measured p,A relations of the urethra in the model lead to the predictions that flow in the flow controlling zone is not always critical but is often in the sub-critical range, that an increase in abdominal pressure can increase the flow under certain conditions, and that hysteresis in the pressure,area relation is correlated to the hysteresis in the p,Q plot. Neurourol. Urodynam. 23:76,85, 2004. Published 2003 Wiley-Liss, Inc. [source] Replication of genetic associations as pseudoreplication due to shared genealogyGENETIC EPIDEMIOLOGY, Issue 6 2009Noah A. Rosenberg Abstract The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence. Genet. Epidemiol. 33:479,487, 2009. © 2009 Wiley-Liss, Inc. [source] A multiple-theory analysis of a diffusion of information technology caseINFORMATION SYSTEMS JOURNAL, Issue 3 2001Richard Baskerville Abstract. This paper describes a multiple-theory analysis of a diffusion of information technology case. Three innovation diffusion models, the interactive model, the linked-chain model and the emergent model, are used to develop an analysis that describes the essential knowledge that each model produces. Rather than develop conflicting stories, each model leads to distinctly different, but complementary, knowledge about the case setting. More generally, the analysis enables us to circumscribe the distinct conceptual domain of each model. These domains define the scope of research questions that can be addressed by each of the innovation diffusion models. In addition to the theoretical implications, the paper also describes the practical indications and actions of the case subjects. [source] Inextensible reinforcement on non-linear elasto-plastic subgrade under oblique pullINTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 18 2008J. T. Shahu Abstract In this paper, a rational analysis of pullout resistance of inextensible sheet reinforcement subjected to oblique end force has been presented considering a non-linear (hyperbolic), elasto-plastic, normal stress,displacement relationship of the subgrade. Under an oblique pull, high normal stresses develop on stronger subgrades, thus mobilizing high shearing resistance at the reinforcement,soil interface. The higher the bearing resistance of the subgrade, the higher the horizontal component of pullout force and the lower the end displacement of the reinforcement. On the other hand, the end displacement at pullout can become very high for weaker subgrades especially at high values of the angle of obliquity. Also, the pullout capacity under oblique loading for weaker subgrades may approach or even fall below the axial pullout capacity at high values of the angle of obliquity. These adverse pullout responses owing to a low value of bearing resistance of subgrade are magnified when the subgrade stiffness is also small. On weaker subgrades, improvement in angle of interface shear is not advisable as this leads to further reduction in the pullout force and increase in the end displacement. Results are compared with back analysis of published test data on model reinforced soil walls. The comparison suggests that the present model leads to a more rational and better prediction of the pullout failure. Copyright © 2008 John Wiley & Sons, Ltd. [source] Correlated, ab initio electron propagators in the study of molecular wires: Application to a single molecular bridge placed between two model leadsINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 15 2007Mark R. Sterling Abstract A correlated, ab initio electron propagator approach is tested for a model system containing 1,4-benzene-dithiolate attached to two gold or two aluminum atoms. Qualitative agreement with available experiment is achieved for the gold dithiolate system. Similar current and conductance curves obtain for both metal leads when the Fermi energy is set to ,1.0 eV. A molecular orbital analysis is given for the gold dithiolate system. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source] Absorption, resonance, and near-resonance Raman studies of the tetracyanoquinodimethane neutral and its monoanion in terms of density functional theory and complete active space self-consistent field methodsINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 8 2006Marcin Makowski Abstract The electronic structure of the 11B1u and 12B3u excited electronic states of the tetracyanoquinodimethane (TCNQ) neutral and its charged derivative are studied within the framework of complete active space self-consistent field (CASSCF) and Becke's three-parameter hybrid method with Lee,Yang,Parr correlation functional (B3LYP) methods applied to the level aug-cc-p-VDZ basis set. Both CASSCF/aug-cc-p-VDZ and B3LYP/aug-cc-p-VDZ treatments provide the ground-state and the excited state geometries; these are then used to assess the Franck,Condon (FC) parameters in the 11B1u state of the neutral TCNQ and in the 12B3u state of the TCNQ monoanion. The quality of numerical results is then tested on the base of available experimental near-resonance and resonance Raman data. The studies are performed in terms of the vibronic model, which takes both FC and mode-mixing (Dushinsky) effects into account. This somewhat simplified vibronic model leads to very good agreement between the theory and the Raman experiments concerning both neutral TCNQ and its monoanion. In particular, the calculated excitation profiles of the ,2 = 2215 cm,1, ,4 = 1389 cm,1, ,5 = 1195 cm,1, and ,9 = 336 cm,1 fundamentals are shown to be in excellent agreement with those for the TCNQ monoanion. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006 [source] Modelling the trend and seasonals within an AIDS model of the demand for alcoholic beverages in the United KingdomJOURNAL OF APPLIED ECONOMETRICS, Issue 2 2002I. A. Moosa The argument that is put forward in this paper is that failure to represent stochastic trend and stochastic seasonality in an AIDS model leads to a misspecified and possibly structurally unstable model. This proposition is verified by estimating an AIDS model of the demand for alcoholic beverages in the United Kingdom. Three versions of the model are estimated, and it is demonstrated that the version allowing for stochastic trend and stochastic seasonality performs better than the other two versions of the model in terms of the diagnostics tests and goodness of fit measures. The best estimated model turns out to possess the properties of having common components and being homogenous. Further empirical testing reveals the presence of stochastic trends and cointegration between the budget shares of beer and wine. The results clearly indicate that there has been a shift away from the consumption of beer towards wine. Copyright © 2002 John Wiley & Sons, Ltd. [source] Transgenerational Obligations: Twenty-first Century Germany and the HolocaustJOURNAL OF APPLIED PHILOSOPHY, Issue 1 2003Doris Schroeder Do the grandchildren of Holocaust perpetrators or the grandchildren of inactive bystanders carry any obligations that are only related to their ancestry? These questions will be at the centre of this investigation. It will be argued that five different models of justification are available for or against transgenerational obligations, namely liberalism, the unique evil argument, the psychological view, a form of consequentialist pragmatism and the community-based approach. Only two of these models stand up to philosophical scrutiny. Applying the community-based model leads to the conclusion that young Germans do indeed have indirect, indeterminate, but strict obligations that transcend generation borders. However, it will be argued that only the obligation of compensation can be restricted to Germans. The remaining two Holocaust-related obligations of prevention and remembrance have to be seen as universal. [source] Paired comparisons for the evaluation of crispness of cereal flakes by untrained assessors: correlation with descriptive analysis and acoustic measurementsJOURNAL OF CHEMOMETRICS, Issue 3 2005Philippe Courcoux Abstract This study investigates the effectiveness of the paired comparison method in the evaluation of a complex sensory attribute by untrained assessors. The crispness perception of cereal flakes by a panel of 100 consumers is measured using a complete block design, and the fitting of the Bradley,Terry,Luce model leads to a ranking of the samples on a crispness intensity scale. A log,linear formulation of the Bradley model provides insight into goodness-of-fit tests and allows the effects of covariates to be incorporated in the prediction of the sensory scores. Results show a high correlation between crispness assessment by consumers and rating of texture attributes by trained assessors. Acoustic emission is shown to have a significant effect on crispness perception, and the power spectra of signals recorded during compression provide a prediction of the crispness of cereal flakes. Copyright © 2005 John Wiley & Sons, Ltd. [source] A valid equation for the well-stirred perfusion limited physiologically based pharmacokinetic model that consistently accounts for the blood,tissue drug distribution in the organ and the corresponding valid equation for the steady state volume of distributionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2010Leonid M. Berezhkovskiy Abstract A consistent account of the assumptions of the well-stirred perfusion limited model leads to the equation for the organ tissue that does not coincide with that often presented in books and papers. The difference in pharmacokinetic profiles calculated by the valid and the commonly used equations could be quite significant, particularly due to contribution of the organs with relatively large perfusion volume, and especially for drugs with small tissue,plasma partition coefficient and high blood,plasma concentration ratio. Application of the valid equation may result in much faster initial drop of drug plasma concentration time curve and significantly longer terminal half-life, especially for low extraction ratio drugs. An equation for the steady state volume of distribution consistent with the well-stirred model described by the valid equation is provided. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:475,485, 2010 [source] Monitoring the corrosion and remediation of reinforced concrete on-site: An alternative approachMATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 4 2005N. Birbilis Abstract Difficulties associated with the interpretation of site data collected over long periods of time from commonly used electrochemical corrosion monitoring techniques often make it difficult to assess the corrosion of reinforcing steel. An alternative approach for the interpretation of data is proposed, based on a model of the quality of passive film upon the steel surface. This model leads to a representation of the corrosion state by means of the relationship, over a long period of time, of the corrosion potential and the logarithm of the Linear Polarization Resistance, since both are functions inter alia of corrosion rate. It is shown that for the reinforced concrete panels tested, data points representing this relationship closely fitted a family of results; allowing the development of a "monitoring control diagram", MCD. The MCD reveals that for a fixed geometry and experimental conditions, a relationship between the corrosion potential and polarization resistance of steel exists, facilitating a useful monitoring tool for assessment of both the corrosion and remediation of reinforced concrete structures. Particular emphasis is placed on the latter in this work. [source] A model to design recreational boat mooring fieldsNAVAL RESEARCH LOGISTICS: AN INTERNATIONAL JOURNAL, Issue 2 2009Ronald E. Giachetti Abstract This article develops a mathematical model and heuristic algorithm to design recreational boating mooring fields. The boating industry is important to the Florida economy, and boat storage is becoming a concern among those in the industry. The mooring field design problem is formulated to maximize the total number of boat feet moored in the mooring field. In the model, we allow two adjacent moorings to overlap, which introduces a risk that under certain conditions the boats on these moorings could contact each other. We identify the conditions when contact is possible and quantify the probability of contact. The mooring field design problem is formulated as a nonlinear mixed-integer programming problem. To solve the problem, we decompose it into two separate models, a mooring radii assignment model and a mooring layout model, which are solved sequentially. The first is solved via exhaustive enumeration and the second via a depth-first search algorithm. Two actual mooring fields are evaluated, and in both cases our model leads to better layouts than ones experts developed manually. The mooring field design model rationalizes the mooring field design and shows that in one case by increasing the risk from 0 to 1%, the mooring efficiency increases from 74.8% to 96.2%. © 2009 Wiley Periodicals, Inc. Naval Research Logistics, 2009 [source] Inflation Uncertainty, Output Growth Uncertainty and Macroeconomic PerformanceOXFORD BULLETIN OF ECONOMICS & STATISTICS, Issue 3 2006Stilianos Fountas Abstract We use a bivariate generalized autoregressive conditionally heteroskedastic (GARCH) model of inflation and output growth to examine the causality relationship among nominal uncertainty, real uncertainty and macroeconomic performance measured by the inflation and output growth rates. The application of the constant conditional correlation GARCH(1,1) model leads to a number of interesting conclusions. First, inflation does cause negative welfare effects, both directly and indirectly, i.e. via the inflation uncertainty channel. Secondly, in some countries, more inflation uncertainty provides an incentive to Central Banks to surprise the public by raising inflation unexpectedly. Thirdly, in contrast to the assumptions of some macroeconomic models, business cycle variability and the rate of economic growth are related. More variability in the business cycle leads to more output growth. [source] Stress induced one-dimensional model for current oscillations at the Si/electrolyte contactPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 7 2009Jürgen Grzanna Abstract A cellular automata is introduced to model the locally resolved oxide thickness, the stress, and the etching rate dynamics at the silicon electrolyte contact along a macroscopically long line (1 mm). Short- and long-range interaction mechanisms are considered to achieve current oscillations. Extended chronoamperometric oscillations are obtained but finally, the oscillations become increasingly damped for the case of a locally acting stress and a locally varying etching rate. The additional incorporation of a small oscillating and long-range interacting nominal etching rate into the model leads to sustained oscillations. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] FCCU simulation based on first principle and artificial neural network modelsASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 6 2009Maria Mihe Abstract A first principle model has been developed for the reactor,regenerator system based on construction and operating data from an industrial fluid catalytic cracking unit (FCCU). The first principle model takes into account the main FCCU subsystems: reactor riser, regenerator, stripper, catalyst circulation lines, air blower, wet gas compressor and main fractionator. A five-lump kinetic scheme has been considered for the reactions taking place in the reactor riser. Subsequently, an artificial neural network (ANN) model has been built for the complex FCCU system. The dynamic simulator, based on the previously developed first principle model, served as the source of reliable data for ANN design, training and testing. The ANN developed model was successfully trained and tested. Comparison between first principle and neural network based model leads to a very good match between the two models. Results show the substantial reduction of the computation time featured by the ANN model compared to the first principle model, demonstrating its potential use for real-time implementation in model-based control algorithms. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd. [source] | ||||||||||||||||