Maximum likelihood estimation of reviewers' acumen in central review setting: categorical data

Successfully evaluating pathologists' acumen could be very useful in improving the concordance of their calls on histopathologic variables. We are proposing a new method to estimate the reviewers' acumen based on their histopathologic calls. The previously proposed method includes redundant parameters that are not identifiable and results are incorrect. The new method is more parsimonious and through extensive simulation studies, we show that the new method relies less on the initial values and converges to the true parameters. The result of the anesthetist data set by the new method is more convincing.     

A Comparative Survey of Automated Parameter-Search Methods for Compartmental Neural Models

One of the most difficult and time-consuming aspects of building compartmental models of single neurons is assigning values to free parameters to make models match experimental data. Automated parameter-search methods potentially represent a more rapid and less labor-intensive alternative to choosing parameters manually. Here we compare the performance of four different parameter-search methods on several single-neuron models. The methods compared are conjugate-gradient descent, genetic algorithms, simulated annealing, and stochastic search. Each method has been tested on five different neuronal models ranging from simple models with between 3 and 15 parameters to a realistic pyramidal cell model with 23 parameters. The results demonstrate that genetic algorithms and simulated annealing are generally the most effective methods. Simulated annealing was overwhelmingly the most effective method for simple models with small numbers of parameters, but the genetic algorithm method was equally effective for more complex models with larger numbers of parameters. The discussion considers possible explanations for these results and makes several specific recommendations for the use of parameter searches on neuronal models.     

Stimulating effect of very low doses of chronic gamma irradiation on the development of chick embryos

A study was made of the influence of chronic gamma-irradiation, with very low doses, of chick embryos during incubation on the dynamics of changes in the parameters characterizing the proliferative activity of cells. The original method is proposed for the analysis of these parameters and the results obtained by this method are discussed.     

Automated identification of subpopulations in flow cytometric list mode data using cluster analysis

The application of K-means (ISODATA) cluster analysis to flow cytometric data is described. The results of analyses of flow cytometric data for mixtures of fluorescent microspheres and samples of peripheral blood mononuclear cells are presented. A method for simultaneously displaying list mode data for any number of parameters, which had previously been applied to a continuous set of parameters such as multi-angle light scattering data, is used to present the results of cluster analysis on physically unrelated parameters; this method allows rapid evaluation of the success of subpopulation identification. The factors that influence automated identification of subpopulations are examined, and methods for determining optimal values for these factors are described.     

Less invasive blood sampling in the animal laboratory: clinical chemistry and haematology of blood obtained by the Triatominae bug Dipetalogaster maximus

Dipetalogaster maximus (Dipmax), a blood-sucking bug belonging to the family Reduviidae, has been used to obtain blood samples, for example for clinical chemistry and haematology, in a variety of zoo animals and wildlife. Using this bug allows stress-free blood sampling as the bug is able to draw blood without the mammal noticing the bug. In laboratory animal science, the need for blood samples from unstressed animals may arise, especially in animal behaviour research. The use of Dipmax bugs may prove a valuable tool for this purpose. To validate the method, we compared an array of standard blood parameters sampled from New Zealand White rabbits, sampled either by the use of bugs or by the conventional method; puncture of vena auricularis caudalis. The overall hypothesis was that there was no significant difference in clinical chemistry and haematological parameters between the bug method and the conventional method. A total of 17 clinical parameters as well as 12 haematological parameters were measured and compared in New Zealand White rabbits. The results showed that for 13 of these 29 analysed parameters, the bug method and the conventional method did not give significantly different results, and the obtained results were thus directly comparable. For the remaining parameters the obtained results were significantly different. However, all parameters were measurable in the bug samples. The influences of the bug metabolism on these parameters are discussed.     

Utilization of spline functions for smoothing fermentation data and for estimation of specific rates

A response surface method of smoothing fermentation data with spline functions is presented. The available electron balance is used to optimally select the values of the smoothing parameters associated with the spline functions. The method is applied to six sets of anaerobic fermentation data in which pure and mixed cultures are grown in batch followed by fed batch culture. Lactobacillus bulgaricus and Streptococcus thermophilus are cultured on 3% dry milk. Measured concentrations of biomass, lactose, galactose, lactic acid, and other acid products are smoothed using spline functions. Values of specific growth rate, specific lactose consumption rate, specific galactose formation rate, and specific acid product formation rate are estimated and the consistency of the results is examined using the available electron balance. The results show that the method works reasonably well, but that an upper bound should be used for the smoothing parameters to obtain accurate estimates of the derivative quantities.     

A Novel Method of Object Detection from a Moving Camera Based on Image Matching and Frame Coupling

A new method based on image matching and frame coupling to handle the problems of object detection caused by a moving camera and object motion is presented in this paper. First, feature points are extracted from each frame. Then, motion parameters can be obtained. Sub-images are extracted from the corresponding frame via these motion parameters. Furthermore, a novel searching method for potential orientations improves efficiency and accuracy. Finally, a method based on frame coupling is adopted, which improves the accuracy of object detection. The results demonstrate the effectiveness and feasibility of our proposed method for a moving object with changing posture and with a moving camera.     

Estimation of muscle active state

A method is presented for the estimation of the complete time course of muscle active state. The method is based on the selection of a proper model for the muscle, consisting of linear and non-linear components, and on the estimation of its parameters from a simple experiment. The model's parameters are estimated, using the least square method, from measurements of a tetanized muscle's response to a change of its length. The time course of the active state is calculated from an isometric twitch tension response of the same muscle. The twitch tension response is taken as the system's output, and the active state as its input. The latter can be estimated since the system parameters have already been estimated from the tetanized muscle experiment. Experiments were performed on the gastrocnemius muscle of frogs and cats. Results are given for the whole active state time course of these muscles. The results show that the peak active state force does not reach tetanic value, and a negative force is generated during the relaxation period. Additional experiments were carried out with the purpose of verifying the existence of this force; however, no conclusive results were obtained.This research was supported by the Julius Silver Institute of Bio-Medical Engineering Sciences, Grant 050-304     

Sensitivity-based adaptive mesh refinement collocation method for dynamic optimization of chemical and biochemical processes

Collocation on finite element (CFE) is an effective simultaneous method of dynamic optimization to increase the profitability or productivity of industrial process. The approach needs to select an optimal mesh of time interval to balance the computational cost with desired solution. A new CFE approach with non-uniform refinement procedure based on the sensitivity analysis for dynamic optimization problems is, therefore, proposed, where a subinterval is further refined if the obtained control parameters have significant effect on the performance index. To improve the efficiency, the sensitivities of state parameters with respect to control parameters are derived from the solution of the discretized dynamic system. The proposed method is illustrated by testing two classic dynamic optimization problems from chemical and biochemical engineering. The detailed comparisons among the proposed method, the CFE with uniform mesh, and other reported methods are also carried out. The research results reveal the effectiveness of the proposed approach.

     

Quantification of chymosin action on nonlabeled kappa-casein-related peptide substrates by ultraviolet spectrophotometry: description of kinetics by the analysis of progress curves

A method is described for quantifying the proteolytic action of the milk-clotting enzyme chymosin on small and medium-sized peptide substrates by monitoring the decrease of absorbance at 230 nm during cleavage. The method is illustrated by the determination of the kinetic parameters of the specific splitting of a kappa-casein-related hexa- and pentadecapeptide by chymosin. The results are in good agreement with those found earlier with the same enzyme/substrate system by using an automated ninhydrin method. Erroneous results were obtained when the kinetic data were derived from one single progress curve. The significance of initial rate measurements for calculating correct kinetic parameters is briefly discussed. The usefulness of single progress curves measured at different initial substrate concentrations for obtaining information about the mechanism of the enzymic reaction is demonstrated.     

Extending the method of mathematically controlled comparison to include numerical comparisons

MOTIVATION: The method of mathematically controlled comparison has been used for some time to determine which of two alternative regulatory designs is better according to specific quantitative criteria for functional effectiveness. In some cases, the results obtained using this technique are general and independent of parameter values and the answers are clear-cut. In others, the result might be general, but the demonstration is difficult and numerical results with specific parameter values can help to clarify the situation. In either case, numerical results with specific parameter values can also provide an answer to the question of how much larger the values might be. In contrast, a more ambiguous result is obtained when either of the alternatives can have the larger value for a given systemic property, depending on the specific values of the parameters. In any case, introduction of specific values for the parameters reduces the generality of the results. Therefore, we have been motivated to develop and apply statistical methods that would permit the use of numerical values for the parameters and yet retain some of the generality that makes mathematically controlled comparison so attractive. RESULTS: We illustrate this new numerical method in a step-by-step application using a very simple didactic example. We also validate the results by comparison with the corresponding results obtained using the previously developed analytical method. The analytical approach is briefly present for reference purposes, since some of the same key concepts are needed to understand the numerical method and the results are needed for comparison. The numerical method confirms the qualitative differences between the systemic behavior of alternative designs obtained from the analytical method. In addition, the numerical method allows for quantification of the differences and it provides results that are general in a statistical sense. For example, the older analytical method showed that overall feedback inhibition in an unbranched pathway makes the system more robust whereas it decreases the stability margin of the steady state. The numerical method shows that the magnitudes of these differences are not comparable. The differences in stability margins (1-2% on average) are small when compared to the differences in robustness (50-100% on average). Furthermore, the numerical method shows that the system with overall feedback responds more quickly to change than the otherwise equivalent system without overall feedback. These results suggest reasons why overall feedback inhibition is such a prevalent regulatory pattern in unbranched biosynthetic pathways.     

A new method for estimating the axis of rotation and the center of rotation.

A new method is presented for estimating the parameters of two different models of a joint. The two models are: (1) A rotational joint with a fixed axis of rotation, also referred to as a hinge joint and (2) a ball and socket model, corresponding to a spherical joint. Given the motion of a set of markers, it is shown how the parameters can be estimated, utilizing the whole data set. The parameters are estimated from motion data by minimizing two objective functions. The method does not assume a rigid body motion, but only that each marker rotates around the same fixed axis of rotation or center of rotation. Simulation results indicate that in situations where the rigid body assumption is valid and when measurement noise is present, the proposed method is inferior to methods that utilize the rigid body assumption. However, when there are large skin movement artefacts, simulation results show the proposed method to be more robust.     

A global approach for sparse representation of uncertainty in Life Cycle Assessments of waste management systems

Purpose

Identification of key inputs and their effect on results from Life Cycle Assessment (LCA) models is fundamental. Because parameter importance varies greatly between cases due to the interaction of sensitivity and uncertainty, these features should never be defined a priori. However, exhaustive parametrical uncertainty analyses may potentially be complicated and demanding, both with analytical and sampling methods. Therefore, we propose a systematic method for selection of critical parameters based on a simplified analytical formulation that unifies the concepts of sensitivity and uncertainty in a Global Sensitivity Analysis (GSA) framework.

Methods

The proposed analytical method based on the calculation of sensitivity coefficients (SC) is evaluated against Monte Carlo sampling on traditional uncertainty assessment procedures, both for individual parameters and for full parameter sets. Three full-scale waste management scenarios are modelled with the dedicated waste LCA model EASETECH and a full range of ILCD recommended impact categories. Common uncertainty ranges of 10 % are used for all parameters, which we assume to be normally distributed. The applicability of the concepts of additivity of variances and GSA is tested on results from both uncertainty propagation methods. Then, we examine the differences in discernibility analyses results carried out with varying numbers of sampling points and parameters.

Results and discussion

The proposed analytical method complies with the Monte Carlo results for all scenarios and impact categories, but offers substantially simpler mathematical formulation and shorter computation times. The coefficients of variation obtained with the analytical method and Monte Carlo differ only by 1 %, indicating that the analytical method provides a reliable representation of uncertainties and allows determination of whether a discernibility analysis is required. The additivity of variances and the GSA approach show that the uncertainty in results is determined by a limited set of important parameters. The results of the discernibility analysis based on these critical parameters vary only by 1 % from discernibility analyses based on the full set, but require significantly fewer Monte Carlo runs.

Conclusions

The proposed method and GSA framework provide a fast and valuable approximation for uncertainty quantification. Uncertainty can be represented sparsely by contextually identifying important parameters in a systematic manner. The proposed method integrates with existing step-wise approaches for uncertainty analysis by introducing a global importance analysis before uncertainty propagation.

     

Texture analysis of cervical cell nuclei by segmentation of chromatin patterns.

Texture parameters of the nuclear chromatin pattern can contribute to the automated classification of specimens on the basis of single cell analysis in cervical cytology. Current texture parameters are abstract and therefore hamper understanding. In this paper texture parameters are described that can be derived from the chromatin pattern after segmentation of the nuclear image. These texture parameters are more directly related to the visual properties of the chromatin pattern. The image segmentation procedure is based on a region grow algorithm which specifically isolates high chromatin density. The texture analysis method has been tested on a data set of images of 112 cervical nuclei on photographic negatives digitized with a step size of 0.125 micron. The preliminary results of a classification trial indicate that these visually interpretable parameters have promising discriminatory power for the distinction between negative and positive specimens.     

Double Diffusive Magnetohydrodynamic (MHD) Mixed Convective Slip Flow along a Radiating Moving Vertical Flat Plate with Convective Boundary Condition

In this study combined heat and mass transfer by mixed convective flow along a moving vertical flat plate with hydrodynamic slip and thermal convective boundary condition is investigated. Using similarity variables, the governing nonlinear partial differential equations are converted into a system of coupled nonlinear ordinary differential equations. The transformed equations are then solved using a semi-numerical/analytical method called the differential transform method and results are compared with numerical results. Close agreement is found between the present method and the numerical method. Effects of the controlling parameters, including convective heat transfer, magnetic field, buoyancy ratio, hydrodynamic slip, mixed convective, Prandtl number and Schmidt number are investigated on the dimensionless velocity, temperature and concentration profiles. In addition effects of different parameters on the skin friction factor, , local Nusselt number, , and local Sherwood number are shown and explained through tables.     

Estimation of Clustering Parameters Using Gaussian Process Regression

We propose a method for estimating the clustering parameters in a Neyman-Scott Poisson process using Gaussian process regression. It is assumed that the underlying process has been observed within a number of quadrats, and from this sparse information the distribution is modelled as a Gaussian process. The clustering parameters are then estimated numerically by fitting to the covariance structure of the model. It is shown that the proposed method is resilient to any sampling regime. The method is applied to simulated two-dimensional clustered populations and the results are compared to a related method from the literature.     

Mathematical correlation between biomaterial and cellular parameters--critical reflection of statistics

For mathematical modelling of the biomaterial-cell contact, it is necessary to find both parameters characterizing physical and chemical properties of the material surface and also such describing the reaction of the adhering cells. Only those material and cell parameters that correlate with each other are applicable to model this contact mathematically. Only few papers are dealing with this special problem. The aim of this paper is to present results of physical/chemical and biological investigations made on differently modified rough titanium implant surfaces in order to find out only the correlating parameters. Furthermore we discuss several ways to apply statistical methods to the correlation problem. Only few ones of all investigated parameters both on material and on cellular side were applicable for correlation. For example we found in our studies that fractal structure parameter topothesy has influence on the spreading behaviour of the osteoblastic cells. However the value of the correlation coefficient and its statistical significance heavily depend on the method of averaging the available data. Especially the biological data (spreading area) were afflicted with relatively high error up to 30%. Averaging of this data masks the true facts. That is why the correlation coefficient considerably decreases if the biological parameters are not averaged. On the other hand, the statistical reliability increases due to the higher number of investigated cases. Critical error discussion is necessary in statistical correlation between material and biological parameters. Often the results are heavily influenced by the statistical handling of data, especially if only few data are available. May be that new unconventional methods like bootstrap method can show a way out of this dilemma.     

一类信号转导通路模型参数辨识中最小应测量状态的确定

建立信号转导通路的数学模型是系统生物学的一个重要目标．但是信号转导通路本身的复杂结构及其所表现出的强非线性特征,使得对该类模型的参数辨识十分困难．参数辨识所需要的测量数据的选择对于辨识结果有重要影响．本文研究了一类信号转导通路模型参数辨识中最小应测量状态的计算问题．给出了用于确定该最小应测量状态的目标函数,通过对目标函数进行简单的运算,确定了用来估计未知参数的最小应测量状态的数量,同时给出了一种计算系统状态对应于未知参数的敏感性系统曲线的新方法．以TNFα诱导的NF-κB信号转导通路为例进行了仿真研究,并给出了仿真结果．     

Determination of human arterial wall parameters from clinical data

This study suggests a method to compute the material parameters for arteries in vivo from clinically registered pressure-radius signals. The artery is modelled as a hyperelastic, incompressible, thin-walled cylinder and the membrane stresses are computed using a strain energy. The material parameters are determined in a minimisation process by tuning the membrane stress to the stress obtained by enforcing global equilibrium. In addition to the mechanical model, the study also suggests a preconditioning of the pressure-radius signal. The preconditioning computes an average pressure-radius cycle from all consecutive cycles in the registration and removes, or reduces, undesirable disturbances. The effect is a robust parameter identification that gives a unique solution. The proposed method is tested on clinical data from three human abdominal aortas and the results show that the material parameters from the proposed method do not differ significantly (p < 0.01) from the corresponding parameters obtained by averaging the result from consecutive cycles.     

Influence of experimental conditions on visco-hyperelastic properties of skeletal muscle tissue using a Box–Behnken design

The Mechanical characterization of skeletal muscles is strongly dependent on numerous experimental design factors. Nevertheless, significant knowledge gaps remain on the characterization of muscle mechanics and a large number of experiments should be implemented to test the influence of a large number of factors. In this study, we propose a design of experiment method (DOE) to study the parameter sensitivity while minimizing the number of tests. A Box-Behnken design was then implemented to study the influence of strain rate, preconditioning and preloading conditions on visco-hyperelastic mechanical parameters of two rat forearm muscles. The results show that the strain rate affects the visco-hyperelastic parameters for both muscles. These results are consistent with previous work demonstrating that stiffness and viscoelastic contributions increase with strain rate. Thus, DOE has been shown to be a valid method to determine the effect of the experimental conditions on the mechanical behaviour of biological tissues such as skeletal muscle. This method considerably reduces the number of experiments. Indeed, the presented study using 3 parameters at 3 levels would have required at least 54 tests per muscle against 14 for the proposed DOE method.