A tracer interaction method for nonlinear pharmacokinetics analysis: application to evaluation of nonlinear elimination

A drug tracer is most commonly applied to get information about the pharmacokinetics (PK) of a drug that is not confounded by an endogenously produced drug or an unknown drug input. An equally important use of tracers that has not been fully recognized is their use in the study of nonlinear PK behavior. In the present study a system analysis is applied to examine the interaction between drug molecules characteristic and intrinsic to any nonlinear process which enables the nonlinearity to be identified and modeled using a drug tracer. The proposed Tracer Interaction Methodology (TIM) forms a general developmental framework for novel methods for examining nonlinear phenomena. Such methods are potentially much more sensitive and accurate than previous methods not exploiting the tracer principle. The methodology proposed is demonstrated in a simulation study and with real data in a specific implementation aimed at determining the Michaelis-Menten (MM) parameters of nonlinear drug elimination while accounting for drug distribution effects. The simulation study establishes that the TIM-based, MM parameter evaluation produces substantially more accurate parameter estimates than a nontracer (NT) conventional method. In test simulations the accuracy of the TIM was in many cases an order of magnitude better than the NT method without evidence of bias. The TIM-based, MM parameter estimation methodology proposed is ideally suitable for dynamic, non-steady-state conditions. Thus, it offers greater applicability and avoids the many problems specific to steady state evaluations previously proposed. TIM is demonstrated in an evaluation of the nonlinear elimination behavior of erythropoietin, a process that likely takes place via receptor-based endocytosis. Due to its high sensitivity, accuracy, and intrinsic nonlinearity the TIM may be suitable for in-vivo studies of receptor binding of the many biotechnology produced peptide drugs and endogenous compounds displaying receptor-mediated elimination.     

Algorithm to Generate a Discrete Element Specimen with Predefined Properties

The discrete element method is a powerful numerical tool in simulating the behavior of granular materials. It bridges the gap between continuum mechanics and physical modeling investigations. In spite of the significant achievements to date, some major problems are yet to be solved including the development of realistic large-scale models with initial conditions similar to those encountered in real problems. This paper introduces a computational method to generate a large-scale packing with predefined porosity and grain-size distribution in three-dimensional space based on a small initial sample packing. The developed method is implemented into an open-source computer code and used to generate specimens with known properties. The results showed that, under static condition, specimens generated using the proposed algorithm exhibited realistic behavior suitable for geotechnical applications. In addition, the controlled structure of the initial sample packing is successfully transferred to the final packing.     

Virtual social environments as a tool for psychological assessment: Dynamics of interaction with a virtual spouse.

Computer games are advocated as a promising tool bridging the gap between the controllability of a lab experiment and the mundane realism of a field experiment. At the same time, many authors stress the importance of observing real behavior instead of asking participants about possible or intended behaviors. In this article, the authors introduce an online virtual social environment, which is inhabited by autonomous agents including the virtual spouse of the participant. Participants can freely explore the virtual world and interact with any other inhabitant, allowing the expression of spontaneous and unprompted behavior. The authors investigated the usefulness of this game for the assessment of interactions with a virtual spouse and their relations to intimacy and autonomy motivation as well as relationship satisfaction with the real-life partner. Both the intimacy motive and the satisfaction with the real-world relationship showed significant correlations with aggregated in-game behavior, which shows that some sort of transference between the real world and the virtual world took place. In addition, a process analysis of interaction quality revealed that relationship satisfaction and intimacy motive had different effects on the initial status and the time course of the interaction quality. Implications for psychological assessment using virtual social environments are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Asymptotic-Numerical Method to Analyze the Postbuckling Behavior, Imperfection-Sensitivity, and Mode Interaction in Frames

The paper presents the formulation and illustrates the application of an asymptotic-numerical (semianalytical) method to analyze the geometrically nonlinear behavior of plane frames. The method adopts an “internally constrained” beam model and involves two distinct procedures: (1) an asymptotic analysis, which employs a perturbation technique to establish a sequence of systems of equilibrium differential equations and boundary conditions, and (2) the successive numerical solution of such systems, by means of the finite element method. This method can be applied to investigate the behavior of frames with arbitrarily complex configurations (member number and orientation) and leads to the determination of analytical expressions which provide: (1) the initial postbuckling behavior of perfect frames and (2) the nonlinear equilibrium paths of frames containing small initial imperfections or acted by primary bending moments, including the influence of eventual buckling mode interaction phenomena. In order to validate and illustrate the application and potential of the proposed method, several numerical results are presented, concerning (1) four validation examples (Euler column and three simple frames—two or three members), for which there exist some (perfect frame) analytical and numerical asymptotic results reported in the literature; (2) a single-bay pitched-roof frame with partially restrained column bases; and (3) a three-bay frame with two leaning columns. These results comprise (1) the initial postbuckling behavior of perfect frames (individual and coupled buckling modes) and (2) geometrically nonlinear equilibrium paths describing the behavior of frames containing initial geometrical imperfections or primary bending moments. In the latter case, most of the semianalytical results are compared with fully numerical values, yielded by finite element analyses performed in the commercial code ABAQUS.     

Exact Solution of Out-of-Plane Problems of an Arch with Varying Curvature and Cross Section

This paper deals with the exact solution of the differential equations for the out-of-plane behavior of an arch with varying curvature and cross section. The differential equations include the shear deformation effect. The cross section of the arch is doubly symmetric. Due to the double symmetry, in-plane and out-of-plane behavior will be uncoupled. However, a coupling of the out-of-plane bending and the torsional response will exist and will be discussed in this study. The governing differential equations of planar arches loaded perpendicular to their plane are solved exactly by using the initial value method. The analytical expressions of the fundamental matrix can be obtained for some cases. It is also possible to use these analytical expressions in order to obtain the displacements and the stress resultants for an arch with any loading and boundary conditions. The examples given in the literature are solved and the results are compared. The analytical expressions of the results are given for some examples.     

Dynamic Performance Simulation of Long-Span Bridge under Combined Loads of Stochastic Traffic and Wind

Slender long-span bridges exhibit unique features which are not present in short and medium-span bridges such as higher traffic volume, simultaneous presence of multiple vehicles, and sensitivity to wind load. For typical buffeting studies of long-span bridges under wind turbulence, no traffic load was typically considered simultaneously with wind. Recent bridge/vehicle/wind interaction studies highlighted the importance of predicting the bridge dynamic behavior by considering the bridge, the actual traffic load, and wind as a whole coupled system. Existent studies of bridge/vehicle/wind interaction analysis, however, considered only one or several vehicles distributed in an assumed (usually uniform) pattern on the bridge. For long-span bridges which have a high probability of the presence of multiple vehicles including several heavy trucks at a time, such an assumption differs significantly from reality. A new “semideterministic” bridge dynamic analytical model is proposed which considers dynamic interactions between the bridge, wind, and stochastic “real” traffic by integrating the equivalent dynamic wheel load (EDWL) approach and the cellular automaton (CA) traffic flow simulation. As a result of adopting the new analytical model, the long-span bridge dynamic behavior can be statistically predicted with a more realistic and adaptive consideration of combined loads of traffic and wind. A prototype slender cable-stayed bridge is numerically studied with the proposed model. In addition to slender long-span bridges which are sensitive to wind, the proposed model also offers a general approach for other conventional long-span bridges as well as roadway pavements to achieve a more realistic understanding of the structural performance under probabilistic traffic and dynamic interactions.     

高速公路绿篱修剪机器人手臂避障路径规划

针对非结构环境下高速公路绿篱修剪机器人手臂实时准确避障问题, 提出一种基于扰动人工势场法的避障路径规划解决方法.根据绿篱隔离带与障碍物分布情况, 设计智能修剪机器人执行机构, 构建包络障碍物简化模型, 分析机械臂与障碍物的碰撞条件, 求解机械臂在修剪过程中的避碰空间.引入斥力场调节策略来优化势场模型, 建立斥力场扰动机制调整斥力影响方式, 消除传统算法中的局部极小点、目标不可达等现象.在避碰空间内, 应用扰动人工势场法对机械臂进行路径规划仿真, 仿真结果表明, 机械臂跳出局部极小点, 灵活顺利避障, 成功抵达目标点, 验证了该方法的有效性和可行性.      

Dynamic Response of Suspension Bridge to High Wind and Running Train

A framework is presented for predicting the dynamic response of long suspension bridges to high winds and running trains. A three-dimensional finite-element model is used to represent a suspension bridge. Wind forces acting on the bridge, including both buffeting and self-excited forces, are generated in the time domain using a fast spectral representation method and measured aerodynamic coefficients and flutter derivatives. Each 4-axle vehicle in a train is modeled by a 27-degrees-of-freedom dynamic system. The dynamic interaction between the bridge and train is realized through the contact forces between the wheels and track. By applying a mode superposition technique to the bridge only and taking the measured track irregularities as known quantities, the number of degrees of freedom of the bridge-train system is significantly reduced and the coupled equations of motion are efficiently solved. The proposed formulation is then applied to a real wind-excited long suspension bridge carrying a railway inside the bridge deck of a closed cross section. The results show that the formulation presented in this paper can predict the dynamic response of the coupled bridge-train systems under fluctuating winds. The extent of interaction between the bridge and train depends on wind speed and train speed.     

When trying to understand detracts from trying to behave: Effects of perspective taking in intergroup interaction.

Four studies demonstrate that perspective taking can backfire in intergroup interaction, leading lower prejudice individuals to treat an outgroup member less positively than they do when they adopt alternative mind-sets; for higher prejudice individuals, perspective taking instead had a positive, albeit less consistent, effect on behavior. The net result was behavior disruption, whereby individuals' treatment of an outgroup member became incongruent with their inner attitudes. This disruption effect was evident for cognitive and affective forms of perspective taking, in ostensible and real face-to-face intergroup interactions, and for feelings of happiness experienced by individuals' interaction partner as well as outside observers' behavior assessments. Results further suggested that self-regulatory effort mediated the effect of perspective taking on intergroup interaction behavior, with the negative consequences of perspective taking for lower prejudice individuals' behavior appearing to stem from complacency rather than trying too hard. Overall, the findings reveal that perspective taking rather than self-focus accounts for the cognitive resource depletion and behavior disruption effects previously demonstrated to stem from evaluative concern in intergroup interaction and indicate that perspective taking may be more reliably helpful outside of intergroup interaction situations than within them. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cultivation of diversity.

Discusses the necessity of using a multidisciplinary approach to social problems and psychology's distinctive contribution through the scientific explanation of human behavior. The psychologist is obligated to differentiate between his personal values or beliefs and the assertions deriving from psychological science. Psychotechnology is needed to provide mediating links between basic research and practical problems. Psychology can also contribute to solving social problems through cultural diffusion of well-established psychological knowledge, illustrated by such broad, orienting concepts as interaction of variables, overlapping of group ranges, multidimensionality of individual differences, and modifiability of behavior. Social problems can be most effectively solved by encouraging diversity of approaches through different disciplines as well as within psychology. In society at large, the cultivation of diversity enriches the culture and protects the individual against undue control from any 1 source. (84 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Design Proposal to Avoid Peeling Failure in FRP-Strengthened Reinforced Concrete Beams

According to the available experimental work, the most common failure in existing structures strengthened by plate bonding is the laminate peeling off. In the last few years, an important effort in the development of mathematical models to avoid premature peeling failures has been made. However, a suitable and reliable design method to predict debonding due to the shear flow between crack discontinuities or at the laminate end is still not available. This paper describes a new design procedure for structures strengthened by plate bonding to avoid peeling failure at any location. After calculating the laminate area required for flexural strengthening, a two-step procedure to prevent peeling failure is proposed. The first step, to avoid peeling failure along the span, is based on a shear-bending interaction diagram associated with the theoretical maximum transferred force between laminate and support along the crack spacing before laminate debonding. This interaction diagram can be obtained through the application of nonlinear fracture mechanics. The second step consists of checking for peeling failure at the laminate end. The bonded length between the laminate end and the nearest crack should be enough to transfer the laminate tensile force acting on this crack. The proposed method has been verified with available experimental results assembled in a database. A good agreement between the experimental and predicted failure load has been obtained. Finally, an application example is presented to show the applicability of the method.     

Estimation of Influence Tensors for Eigenstressed Multiphase Elastic Media with Nonaligned Inclusion Phases of Arbitrary Ellipsoidal Shape

The analysis of microheterogeneous materials exhibiting eigenstressed and/or eigenstrained phases requires an estimation of eigenstrain influence tensors. Within the framework of continuum micromechanics, we here derive these tensors from extended Eshelby-Laws matrix-inclusion problems, considering, as a new feature, an auxiliary matrix eigenstress. The auxiliary matrix eigenstress is a function of all phase eigenstresses and, hence, accounts for eigenstress interaction. If all material phases are associated with one and the same Hill tensor, the proposed method degenerates to the well-accepted transformation field analysis. Hence, the proposed concept can be interpreted as an extension of the transformation field analysis toward consideration of arbitrarily many Hill tensors, i.e., as an extension toward heterogeneous elastic media comprising inclusion phases with an arbitrary ellipsoidal shape and with arbitrary spatial orientation. This is of particular interest when studying heterogeneous media consisting of constituents with nonspherical phase shapes, e.g., cement-based materials including concrete, or bone. As for polycrystals studied by means of the self-consistent scheme, the auxiliary matrix eigenstress turns out to be equal to the eigenstresses homogenized over the representative volume element (RVE), which is analogous to the self-consistent assumption that the auxiliary stiffness is the average stiffness of the RVE. The proposed method opens the door for micromechanics-based modeling of a great variety of composite phase behaviors characterized by eigenstresses or eigenstrains, e.g., thermoelasticity, poroelasticity, drying-shrinkage, as well as general forms of inelastic behavior, damage, fatigue, and fracture.     

Fast Bayesian FFT Method for Ambient Modal Identification with Separated Modes

Previously a Bayesian theory for modal identification using the fast Fourier transform (FFT) of ambient data was formulated. That method provides a rigorous way for obtaining modal properties as well as their uncertainties by operating in the frequency domain. This allows a natural partition of information according to frequencies so that well-separated modes can be identified independently. Determining the posterior most probable modal parameters and their covariance matrix, however, requires solving a numerical optimization problem. The dimension of this problem grows with the number of measured channels; and its objective function involves the inverse of an ill-conditioned matrix, which makes the approach impractical for realistic applications. This paper analyzes the mathematical structure of the problem and develops efficient methods for computations, focusing on well-separated modes. A method is developed that allows fast computation of the posterior most probable values and covariance matrix. The analysis reveals a scientific definition of signal-to-noise ratio that governs the behavior of the solution in a characteristic manner. Asymptotic behavior of the modal identification problem is investigated for high signal-to-noise ratios. The proposed method is applied to modal identification of two field buildings. Using the proposed algorithm, Bayesian modal identification can now be performed in a few seconds even for a moderate to large number of measurement channels.     

Real-Time Substructure Tests Using Hydraulic Actuator

A new real-time substructure method for testing systems under dynamic loading is described. The method separates a complex system into a physical, possibly nonlinear, subsystem (to be tested experimentally at large scale) and a surrounding linear system, modeled numerically. The two subsystems interact in real time allowing realistic time-dependent nonlinear behavior to take place. This behavior may be impossible to model computationally, and the method overcomes problems associated with scaling and time-dependent effects associated with current shaking table and pseudodynamic test methods. Dynamic forces are applied to the numerical model, and the resulting displacements at the interface between the two subsystems are applied to the physical system using servohydraulic actuators. The restoring forces are then measured and fed back to the numerical model, so that the response for the next time step can be calculated. The technique can be applied to a wide range of complex, linear∕nonlinear systems such as structures with localized plastic deformation, soil-structure interaction, or vehicle-suspension interaction. The method is demonstrated for both single and multi-degree-of-freedom systems, using a single actuator to apply displacements to a physical specimen. Comparisons between experimental and theoretical results show excellent agreement.     

Relative Periodic Motion of a Rigid Body Pendulum on an Ellipse

In this paper, the properties of the relative periodic motions of a rigid body suspended on an elastic string in a vertical plane are considered. The supported point of this pendulum moves on an elliptic path with the rigid body suspended at the end point of the pendulum. Applying Lagrange’s equation, the equations of motion are obtained in terms of small parameter (ε). These equations represent a quasi-linear system of second order, which can be solved in terms of generalized coordinates Θ, Φ, and β using the method of small parameters. At the end, a discussion of the motion and a conclusion of the results are considered to show the orientation of the body and the geometric interpretation of this motion at any instant of time. Also, computerized data with graphical representations of the solutions are given for describing the behavior of the body in some periods of time.     

An integral equation model for intracardiac electrogram sensing

Electrogram sensed by an intracardiac electrode has long been characterized based on two approaches: 1) presume that the electrode is very small and does not disturb the potential prior to applying the electrode, and 2) take an average of the prior potential over the electrode surface. In fact, any intracardiac sensing electrode has a finite surface area where electrical charges are induced and disturb the external potential field, thus, the sensed potential is different from the potential prior to placing the electrode. In this paper, an integral equation model is proposed based on the current continuity equation in homogeneous myocardial medium. The new model can accurately characterize the electrogram sensed by an electrode with a non-negligible surface area and a load impedance. The new model can be solved numerically via the method of moments to obtain the potential induced on the electrode surface by an arbitrary dipole volume source. As an application of the proposed theory, several electrode configurations with different loads have been analyzed with an intent to show that a finite electrode surface will significantly reduce the electrogram peak amplitude and slope, and a load impedance lower than 20 k omega will also degrade the electrogram sensitivity.     

Practice of computer use in radiotherapy planning

The main problems of radiotherapy planning are discussed with respect to use of computers now being available for a greater number of centers. One of the most essential premises is apart from clear ideas on a modern target volume concept - a sufficiently high speed in producing realistic summarized isodose contours for any radiation therapy arrangement in any individual patient's cross section outline. This problem being solved, those individual summarized isodose figures have to be critically evaluated and therefore the importance of applicable meaningful optimization criteria come into account. The properties of such criteria, which must be quantifiable, generally applicable and really relevant for judgement on quality of a plan, had to be accepted, before automatic optimization procedures could be developed; principles involved are presented. By means of a short series of examples, namely 60Co fixed field combinations with and without use of wedges, combinations of arc therapy for a number of clinical tasks. It has been pointed out, that most experienced estimate by the eye would have been by far insufficient when compared to the automized computer optimization when using such simple criteria as 1. homogeneity of absorbed dose within target volume, 2. numerically limited absorbed dose within areas of risk, 3. as low as possible radiation effects to all "outside areas". It seems to be a real danger, that so called isodose libraries, how high their merits might be estimated, may change into an "isodose bcemetery", unless we'll be successful for each individual clinical case by use of computers, which are now prepared to supply the best possible variant of the standard plan or the primary radiotherapy idea. Regular use of computers in such a way will furthermore give an incomparable documentation material.     

Conservative Scheme for Numerical Modeling of Flow in Natural Geometry

A numerical model is proposed to compute one-dimensional open channel flows in natural streams involving steep, nonrectangular, and nonprismatic channels and including subcritical, supercritical, and transcritical flows. The Saint-Venant equations, written in a conservative form, are solved by employing a predictor-corrector finite volume method. A recently proposed reformulation of the source terms related to the channel topography allows the mass and momentum fluxes to be precisely balanced. Conceptually and algorithmically simple, the present model requires neither the solution of the Riemann problem at each cell interface nor any special additional correction to capture discontinuities in the solution such as artificial viscosity or shock-capturing techniques. The resulting scheme has been extensively tested under steady and unsteady flow conditions by reproducing various open channel geometries, both ideal and real, with nonuniform grids and without any interpolation of topographic survey data. The proposed model provides a versatile, stable, and robust tool for simulating transcritical sections and conserving mass.     

Distributed Augmented Reality for Visualizing Collaborative Construction Tasks

Augmented reality is a visualization method in which virtual objects are aligned with the real world and the viewer can interact with the virtual objects in real time. In this paper, a new methodology called distributed augmented reality for visualizing collaborative construction tasks (DARCC) is proposed. Using this methodology, virtual models of construction equipment can be operated and viewed by several operators to interactively simulate construction activities on the construction site in augmented reality mode. The paper investigates the design issues of DARCC including tracking and registration, object modeling, engineering constraints, and interaction and communication methods. The DARCC methodology is implemented in a prototype system and tested in a case study about a bridge deck rehabilitation project.     

Generalized Masing Approach to Modeling Hysteretic Deteriorating Behavior

The modeling of hysteretic behavior is of significant importance in several areas, including civil engineering and mechanics. This paper focuses on finding a method for modeling hysteretic behavior that is simple and efficient in terms of capturing the response and retaining the memory, if any, and at the same time is proper for use in physically meaningful modeling and identification of the system with few parameters. A distributed-element model (DEM) capable of capturing deterioration is used as a starting point, and its characteristics are studied, with a particular focus on the way memory is stored in the model. It is observed that keeping track of the response at a few of the past extremes of input displacement, called the Sequence of Dominant Alternating Extremes, is enough for representing the effect of history. The relation of this behavior to a generalized Masing model is studied. A set of rules is proposed which is a generalization of the Masing rules and can capture the deteriorating (or nondeteriorating) response of DEMs with any distribution of element yield displacement thresholds to any arbitrary loading. The presented formulation provides a framework for efficient modeling and identification of dynamic models of very different characteristics with only a few physically meaningful parameters.