Heritability of Wing Morphology in a Natural Population of Drosophila gouveai

The natural and laboratory heritabilities of a series of parameters related to wing size and shape were estimated in a population of Drosophila gouveai (repleta group) under field and laboratory conditions. A morphometric analysis was done using 17 wing parameters related to wing landmark positions obtained using the method of the best adjustment of an ellipse to the wing edge. Three parameters (thetaA, thetaC and thetaD) showed highly significant heritability in the wild (average 0.61), whereas only wing size (W(SI)) had significant heritability in the laboratory (0.71). The additive genetic variance of most parameters was greater in the wild than in the laboratory. These results showed that some parameters possessed a substantial genetic additive component in their phenotypic variance, and that morphometric parameters of D. gouveai wings are appropriate quantitative markers for assessing morphological differentiation among populations.     

An unbiased sensitivity analysis reveals important parameters controlling periodicity of circadian clock

To assess the importance of model parameters in kinetic models, sensitivity analysis is generally employed to provide key measures. However, it is quite often that no information is available for a significant number of parameters in biochemical models. Therefore, the results of sensitivity analysis that heavily rely on the accuracy of parameters are largely ambiguous. In this study, we propose a computational approach to determine the relative importance of parameters controlling the performance of the circadian clock in Drosophila. While previous attempts to sensitivity analysis largely depend on the knowledge of model parameters which are generally unknown, our study depicts a consistent picture of sensitivity assessment for a large number of parameters, even when the values of these parameters are not available in vivo. The resulting parametric sensitivity analysis suggests that PER/TIM negative loop is critical to maintain the stable periodicity of the circadian clock, which is consistent to the previously experimental and computational findings. Furthermore, our analysis generates a rich hypothesis of important parameters in the circadian clock that can be further tested experimentally. This approach can also be extended to assess the sensitivity of parameters in any biochemical system where a large number of parameters have unknown values. Biotechnol. Bioeng. 2010; 105: 250–259. © 2009 Wiley Periodicals, Inc.     

X-ray diagnosis of different forms of Hirschsprung's disease in children

The purpose of this study was to examine and compare X-ray signs and roentgenometric parameters in different forms of childhood Hirschsprung's disease for their more accurate diagnosis. A hundred and thirty-eight children with different forms of Hirschsprung's disease were followed up. Among them, the children with a supershort segment of the disease amounted to 55%. All the children underwent a comprehensive examination including barium irrigography according to the procedure described by M.D. Levin, followed by an estimation of roentgenometric parameters. The long forms of Hirschsprung's disease had characteristic X-ray symptoms and their appropriate roentgenometric parameters. The supershort segment of the disease had not a complete complex of characteristic X-ray symptoms and its roentgenometric parameters were in direct opposition to the similar parameters in the long form of this disease.     

Estimation of kinetic parameters in a structured yeast model using regularisation.

In this work, a procedure for estimating kinetic parameters in biochemically structured models was developed. The approach is applicable when the structure of a kinetic model has been set up and the kinetic parameters should be estimated. The procedure consists of five steps. First, initial values were found in or calculated from literature. Hereafter using sensitivity analysis the most sensitive parameters were identified. In the third step physiological knowledge was combined with the parameter sensitivities to manually tune the most sensitive parameters. In step four, a global optimisation routine was applied for simultaneous estimation of the most sensitive parameters identified during the sensitivity analysis. Regularisation was included in the simultaneous estimation to reduce the effect of insensitive parameters. Finally, confidence intervals for the estimated parameters were calculated. This parameter estimation approach was demonstrated on a biochemically structured yeast model containing 11 reactions and 37 kinetic constants as a case study.     

Influence of body segment parameters and modeling assumptions on the estimate of center of mass trajectory

This study sought to determine the effect of inaccuracies in body segment parameters and modeling assumptions on the estimate of antero-posterior center of mass (COM) trajectory. Four different methods, one based on segmental kinematics, and three methods based on kinetic recordings were compared via simulation. Kinematic patterns (quiet stance, ankle-related sway, hip-ankle-related sway, sit-up and sit-up-sit-down) were tested with a 2D four-link model of the body and the ground reaction force vector was obtained by inverse dynamics. Errors in the estimation of body segment parameters were simulated by applying a +/-10% variation to one or more parameters at a time. These errors propagated differently to the COM estimated location between methods, between parameters within the same method, and between tasks. The kinematics-based method was the most sensitive to body segment parameters, with special regards to segment lengths and head-arms-trunk parameters. Root mean square error between estimated and simulated COM location reached 19mm in balance-related tasks and 38.3mm in sit-up-sit-down. The kinetics-based methods were largely less sensitive to inaccuracies in body segment parameters. In particular, the technique proposed by Zatsiorsky and King (J. Biomech. 31 (1998) 161), was completely insensitive to segment parameters. On the other hand the kinetics-based methods showed an intrinsic estimation error, due to the underlying model assumptions. The methods based on the double integration of horizontal force had better outcomes with tasks challenging such assumptions, with a maximal error in COM location of 15mm in the sit-up-sit-down. The method proposed by Shimba (J. Biomech. 17 (1984) 53) showed the best trade-off between sensitivity to body segment parameters and estimation performances given the ideal test conditions.     

Determination of elastomeric foam parameters for simulations of complex loading

BACKGROUND: Finite element (FE) analysis has shown promise for the evaluation of elastomeric foam personal protection devices. Although appropriate representation of foam materials is necessary in order to obtain realistic simulation results, material definitions used in the literature vary widely and often fail to account for the multi-mode loading experienced by these devices. This study aims to provide a library of elastomeric foam material parameters that can be used in FE simulations of complex loading scenarios. METHOD OF APPROACH: Twelve foam materials used in footwear were tested in uni-axial compression, simple shear and volumetric compression. For each material, parameters for a common compressible hyperelastic material model used in FE analysis were determined using: (a) compression; (b) compression and shear data; and (c) data from all three tests. RESULTS: Material parameters and Drucker stability limits for the best fits are provided with their associated errors. The material model was able to reproduce deformation modes for which data was provided during parameter determination but was unable to predict behavior in other deformation modes. CONCLUSIONS: Simulation results were found to be highly dependent on the extent of the test data used to determine the parameters in the material definition. This finding calls into question the many published results of simulations of complex loading that use foam material parameters obtained from a single mode of testing. The library of foam parameters developed here presents associated errors in three deformation modes that should provide for a more informed selection of material parameters.     

Markovian analysis of cervical cell images.

Markovian analysis is a method to measure optical texture based on gray-level transition probabilities in digitized images. Experiments are described that investigate that classification performance of parameters generated by Markovian analysis. Results using Markov texture parameters show that the selection of a Markov step size strongly affects classification error rates and the number of parameters required to achieve the maximum correct classification rates. Markov texture parameters are shown to achieve high rates of correct classification in discriminating images of normal from abnormal cervical cell nuclei.     

A general kinetic analysis of transport. Tests of the carrier model based on predicted relations among experimental parameters.

The analysis of transport kinetics has lacked both a unified treatment in which general rate equations are written entirely in terms of experimental parameters, and a convention by which these parameters may be designated in a concise yet immediately recognizable manner. Such a treatment is presented here in an easily accessible form, and a simple system of nomenclature is proposed resembling that in use in enzyme kinetics. The treatment is independent of assumptions about rate-limiting steps in transport, and applies to both active and facilitated systems, including obligatory exchange. A single substrate is characterized by twelve different parameters, only five of which are required in theory to calculate the others. If a second substrate is present on the trans side of the membrane there are six more parameters. All eighteen parameters are linked by multiple relationships which provide a complete set of rejection criteria for the generalized form of the mobile carrier. Relationships among parameters are also defined that give information on the rate-limiting steps in transport. Equations governing any individual experiment, involving only experimental parameters, are easily written out from the general expressions, for example under conditions of zero trans and infinite trans flux, equilibrium exchange, or competitive inhibition.     

Use of an oxygen microsensor for the determination of intrinsic kinetic parameters of an immobilized oxygen reducing enzyme

An oxygen microsensor was used to measure internal oxygen profiles in biocatalyst particles of different diameter and activity. The particles were made of agarose gel and contained an oxygen reducing enzyme, L-lactate mono-oxygenase. The kinetics of the enzyme could be well described by the Michaelis-Menten equation. From the internal substrate concentration profile the intrinsic kinetic parameters were determined by means of fitting a simulated profile to the measurements, using Marquardt's algorithm. The intrinsic kinetic parameters found following this procedure appeared to be independent of particle radius or enzyme loading used, proving the method to be reliable. These parameters were also compared with the kinetic parameters of the free enzyme which were determined in a biological oxygen monitoring system. The intrinsic kinetic parameters showed a decrease with a factor 2.3 for V(m) value and with a factor 2.7 for the K(m) value compared to the parameters for the free enzyme. From this the conclusion can be drawn that the immobilization as such or the carrier material not only can have an effect on the maximum intrinsic conversion rate (V(m)) but also on the affinity of the enzyme (K(m)) for oxygen.     

Statistical aspects of the relation of the radioprotective action of mercaptoethylamine derivatives and analogs to their electron parameters

Numerous S-containing substances were used to study the radioprotective efficiency of the preparations depending on their microscopic characteristics. The method of statistical comparison of the qualitative parameters was used to show that the energy parameters were the most informative electron characteristics of the molecules. Each of these parameters correlated with the physicochemical processes induced in a biological system by ionizing radiation. Quantitative estimates were made associating the protective efficiency of the substances under study with variations in the electron parameters.     

Nonmonotonous Changes in Metabolic Parameters of Tissues and Cells under Action of Ionizing Radiation on Animal

A nonmonotonous relationship between changes of metabolic parameters of tissues and cells of animal and radiation dose were discussed. Under acute irradiation of animals the nonmonotonous dose-response curve for metabolic parameters of tissues and cells were found. The nonmonotonous dose-response curves of metabolic and functional tissues and cells parameters were also revealed upon chronic irradiation of animals at a low dose-rate. The nonmonotonous shape of dose-response curves may be explained on the basis of nonmonotonous kind of the time-course of metabolic response after irradiation. Living cells were supposed to possess a fundamental property in response to action of different stress agents by nonmonotonous changes of cell metabolism. This response was damping in time oscillation of the value of metabolic parameters around the normal level. Amplitudes and periods of oscillations in these changes of metabolic parameters could be observed. In case of chronic irradiation at a low dose-rate the metabolic and functional parameters showed some modified oscillation during irradiation. The nonmonotonous type of changes in metabolic and functional parameters of tissue and cell by chronic low dose-rate irradiation threw some new light on the peculiarities of biological effects of chronic irradiation.     

利用模拟退火算法优化Biome-BGC模型参数

生态过程模型建立在明确的机理之上,能够较好地模拟陆地生态系统的行为和特征,但模型众多的参数,成为模型具体应用的瓶颈。本文以Biome-BGC模型为例,采用模拟退火算法,对其生理、生态参数进行优化。在优化过程中,先对待优化参数进行了选择,然后采取逐步优化的方法进行优化。结果表明,使用优化后的参数,模型模拟结果与实际观测更为接近,参数优化能有效地降低模型模拟的不确定性。文中参数优化的过程和方法,可为生态模型的参数识别和优化提供一种实例和思路,有助于生态模型应用区域的扩展。     

Parametric study of the swimming performance of a fish robot propelled by a flexible caudal fin

In this paper, we aim to study the swimming performance of fish robots by using a statistical approach. A fish robot employing a carangiform swimming mode had been used as an experimental platform for the performance study. The experiments conducted aim to investigate the effect of various design parameters on the thrust capability of the fish robot with a flexible caudal fin. The controllable parameters associated with the fin include frequency, amplitude of oscillation, aspect ratio and the rigidity of the caudal fin. The significance of these parameters was determined in the first set of experiments by using a statistical approach. A more detailed parametric experimental study was then conducted with only those significant parameters. As a result, the parametric study could be completed with a reduced number of experiments and time spent. With the obtained experimental result, we were able to understand the relationship between various parameters and a possible adjustment of parameters to obtain a higher thrust. The proposed statistical method for experimentation provides an objective and thorough analysis of the effects of individual or combinations of parameters on the swimming performance. Such an efficient experimental design helps to optimize the process and determine factors that influence variability.     

Bayesian Inference of Initial Models in Cryo-Electron Microscopy Using Pseudo-atoms

Single-particle cryo-electron microscopy is widely used to study the structure of macromolecular assemblies. Tens of thousands of noisy two-dimensional images of the macromolecular assembly viewed from different directions are used to infer its three-dimensional structure. The first step is to estimate a low-resolution initial model and initial image orientations. This is a challenging global optimization problem with many unknowns, including an unknown orientation for each two-dimensional image. Obtaining a good initial model is crucial for the success of the subsequent refinement step. We introduce a probabilistic algorithm for estimating an initial model. The algorithm is fast, has very few algorithmic parameters, and yields information about the precision of estimated model parameters in addition to the parameters themselves. Our algorithm uses a pseudo-atomic model to represent the low-resolution three-dimensional structure, with isotropic Gaussian components as moveable pseudo-atoms. This leads to a significant reduction in the number of parameters needed to represent the three-dimensional structure, and a simplified way of computing two-dimensional projections. It also contributes to the speed of the algorithm. We combine the estimation of the unknown three-dimensional structure and image orientations in a Bayesian framework. This ensures that there are very few parameters to set, and specifies how to combine different types of prior information about the structure with the given data in a systematic way. To estimate the model parameters we use Markov chain Monte Carlo sampling. The advantage is that instead of just obtaining point estimates of model parameters, we obtain an ensemble of models revealing the precision of the estimated parameters. We demonstrate the algorithm on both simulated and real data.     

生态过程模型敏感参数最优取值的时空异质性分析——以BIOME-BGC模型为例

生态过程模型是当前研究陆地生态系统水循环、碳循环有力的工具,但此类模型参数众多,参数的合理取值对模型模拟结果有重要影响.以往研究对模型参数的敏感性以及参数的优化取值有诸多的分析和讨论,但有关参数最优取值的时空异质性关注较少.本文以BIOME-BGC模型为例,在常绿阔叶林、落叶阔叶林、C3草地3种植被类型下,通过构建敏感性判别指数,筛选出模型的敏感参数,并在每种植被类型下选取两个试验站点,使用模拟退火算法结合实测通量数据构建目标函数,获取各站点敏感参数逐月的最优取值,然后构建时间异质性判别指数、空间异质性判别指数和时空异质性判别指数对模型敏感参数最优取值的时空异质性进行定量分析.结果表明:BIOME-BGC模型在3种植被类型下遴选出的敏感参数大部分一致,少数有差异,但参数的敏感性强弱在不同植被类型下的表现不尽相同;BIOME-BGC模型敏感参数的最优取值,大都具有不同程度的时空异质性,但不同植被类型下,敏感参数最优取值的时空异质性表现各异;敏感参数中与植被生理、生态相关的参数,其时空异质性相对较小,而与环境、物候相关的参数,其时空异质性普遍较大;在3种植被类型下,模型敏感参数最优取值的时间异质性与空间异质性表现出显著的线性相关性;依据其最优取值的时空异质性,可对BIOME-BGC模型敏感参数进行类型划分,以便在实践应用中采取不同的参数率定策略.本研究结论有助于加深对生态过程模型参数特性及最优取值的理解,可为实践应用中模型参数的合理取值提供一种思路和参考.     

Effect of Orientation of Fibers and Holes on the Radial Strain Amplification of Campaniform sensilla

##正## In this paper,a structural analysis is performed to gain insights on the synergistic mechanical amplification effect thatCampaniform sensilla have when combined in an array configuration.In order to simplify the analysis performed in this preliminaryinvestigation,an array of four holes in a single orthotropic lamina is considered.Firstly,a Finite Element Method(FEM) analysis is performed to discretely assess the influence that different geometrical parameters have on the mechanicalamplification properties of the array.Secondly,an artificial neural network is used to obtain an approximated multi-dimensionalcontinuous function,which models the relationship between the geometrical parameters and the amplification properties of thearray.Thirdly,an optimization is performed to identify the geometrical parameters yielding the maximum mechanical amplification.Finally,results are validated with an additional FEM simulation performed by varying geometrical parameters in theneighborhood of the identified optimal parameters.The method proposed in this paper can be fully automated and used to solvea wide range of optimization problems aimed at identifying optimal configurations of strain sensors inspired by Campaniformsensilla.     

A general kinetic analysis of transport Tests of the carrier model based on predicted relations among experimental parameters

The analysis of transport kinetics has lacked both a unified treatment in which general rate equations are written entirely in terms of experimental parameters, and a convention by which these parameters may be designated in a concise yet immediately recognizable manner. Such a treatment is presented here in an easily accessible form, and a simple system of nomenclature is proposed resembling that in use in enzyme kinetics. The treatment is independent of assumptions about rate-limiting steps in transport, and applies to both active and facilitated systems, including obligatory exchange. A single substrate is characterized by twelve different parameters, only five of which are required in theory to calculate the others. If a second substrate is present on the trans side of the membrane there are six more parameters. All eighteen parameters are linked by multiple relationships which provide a complete set of rejection criteria for the generalized form of the mobile carrier. Relationships among parameters are also defined that give information on the rate-limiting steps in transport. Equations governing any individual experiment, involving only experimental parameters, are easily written out from the general expressions, for example under conditions of zero trans and infinite trans flux, equilibrium exchange, or competitive inhibition.     

A modified pseudolikelihood approach for analysis of longitudinal data

We consider the analysis of longitudinal data when the covariance function is modeled by additional parameters to the mean parameters. In general, inconsistent estimators of the covariance (variance/correlation) parameters will be produced when the "working" correlation matrix is misspecified, which may result in great loss of efficiency of the mean parameter estimators (albeit the consistency is preserved). We consider using different "working" correlation models for the variance and the mean parameters. In particular, we find that an independence working model should be used for estimating the variance parameters to ensure their consistency in case the correlation structure is misspecified. The designated "working" correlation matrices should be used for estimating the mean and the correlation parameters to attain high efficiency for estimating the mean parameters. Simulation studies indicate that the proposed algorithm performs very well. We also applied different estimation procedures to a data set from a clinical trial for illustration.     

Bayesian analysis of amino acid substitution models

Models of amino acid substitution present challenges beyond those often faced with the analysis of DNA sequences. The alignments of amino acid sequences are often small, whereas the number of parameters to be estimated is potentially large when compared with the number of free parameters for nucleotide substitution models. Most approaches to the analysis of amino acid alignments have focused on the use of fixed amino acid models in which all of the potentially free parameters are fixed to values estimated from a large number of sequences. Often, these fixed amino acid models are specific to a gene or taxonomic group (e.g. the Mtmam model, which has parameters that are specific to mammalian mitochondrial gene sequences). Although the fixed amino acid models succeed in reducing the number of free parameters to be estimated--indeed, they reduce the number of free parameters from approximately 200 to 0--it is possible that none of the currently available fixed amino acid models is appropriate for a specific alignment. Here, we present four approaches to the analysis of amino acid sequences. First, we explore the use of a general time reversible model of amino acid substitution using a Dirichlet prior probability distribution on the 190 exchangeability parameters. Second, we then explore the behaviour of prior probability distributions that are'centred' on the rates specified by the fixed amino acid model. Third, we consider a mixture of fixed amino acid models. Finally, we consider constraints on the exchangeability parameters as partitions,similar to how nucleotide substitution models are specified, and place a Dirichlet process prior model on all the possible partitioning schemes.