A simple kinetic model for dynein oscillatory activity

A kinetic model for dynein, a molecular motor, complexed with microtubule fragments, is considered. The model explains the experimental observations of oscillatory movements in surprisingly simple axonemal fragments perfused by the ATP solution. The model explains at first time the oscillatory dynein activity as a phenomenon induced by two dynein heads cooperative interaction in the axoneme. The oscillation form, frequency, and amplitude, observed for the model, are close to these experimental characteristics. Kinetic parameters, used in the model, are close to the known experimental parameters.     

Computation of a Stabilizing Set of Feedback Matrices bf a Large-scale Nonlinear Musculoskeletal Dynamic Model

The purpose of this study is to present a general mathematical framework to compute a set of feedback matrices which stabilize an unstable nonlinear anthropomorphic musculoskeletal dynamic model. This method is activity specific and involves four fundamental stages. First, from muscle activation data (input) and motion degrees-of-freedom (output) a dynamic experimental model is obtained using system identification schemes. Second, a nonlinear musculoskeletal dynamic model which contains the same number of muscles and degrees-of-freedom and best represents the activity being considered is proposed. Third, the nonlinear musculoskeletal model (anthropomorphic model) is replaced by a family of linear systems, parameterized by the same set of input/ output data (nominal points) used in the identification of the experimental model. Finally, a set of stabilizing output feedback matrices, parameterized again by the same set of nominal points, is computed such that when combined with the anthropomorphic model, the combined system resembles the structural form of the experimental model. The method is illustrated in regard to the human squat activity.     

Computation of a stabilizing set of feedback matrices of a large-scale nonlinear musculoskeletal dynamic model

The purpose of this study is to present a general mathematical framework to compute a set of feedback matrices which stabilize an unstable nonlinear anthropomorphic musculoskeletal dynamic model. This method is activity specific and involves four fundamental stages. First, from muscle activation data (input) and motion degrees-of-freedom (output) a dynamic experimental model is obtained using system identification schemes. Second, a nonlinear musculoskeletal dynamic model which contains the same number of muscles and degrees-of-freedom and best represents the activity being considered is proposed. Third, the nonlinear musculoskeletal model (anthropomorphic model) is replaced by a family of linear systems, parameterized by the same set of input/output data (nominal points) used in the identification of the experimental model. Finally, a set of stabilizing output feedback matrices, parameterized again by the same set of nominal points, is computed such that when combined with the anthropomorphic model, the combined system resembles the structural form of the experimental model. The method is illustrated in regard to the human squat activity.     

Evaluation of a Hill based muscle model for the energy cost and efficiency of muscular contraction

The purpose of this study was to evaluate a Hill-based mathematical model of muscle energetics and to disclose inconsistencies in existing experimental data. For this purpose, we simulated iso-velocity contractions of mouse fast twitch EDL and slow twitch SOL fibers, and we compared the outcome to experimental results. The experimental results were extracted from two studies published in the literature, which were based on the same methodology but yielded different outcomes (B96 and B93). In the model, energy cost was modeled as the sum of heat and work. Parameters used to model heat rate were entirely independent of the experimental data-sets. Parameters describing the mechanical behavior were derived from both experimental studies. The model was found to accurately predict the muscle energetics and mechanical efficiency of data-set B96. The model could not, however, replicate the energetics and efficiency of SOL and EDL that were found in data-set B93. The model overestimated the shortening heat rate of EDL but, surprisingly, also the mechanical work rate for both muscles. This was surprising since mechanical characteristics of the model were derived directly from the experimental data. It was demonstrated that the inconsistencies in data-set B93 must have been due to some unexplained confounding artifact. It was concluded that the presented model of muscle energetics is valid for iso-velocity contractions of mammalian muscle since it accurately predicts experimental results of an independent data-set (B96). In addition, the model appeared to be helpful in revealing inconsistencies in a second data-set (B93).     

Subsite mapping of enzymes. Depolymerase computer modelling.

We have developed a depolymerase computer model that uses a minimization routine. The model is designed so that, given experimental bond-cleavage frequencies for oligomeric substrates and experimental Michaelis parameters as a function of substrate chain length, the optimum subsite map is generated. The minimized sum of the weighted-squared residuals of the experimental and calculated data is used as a criterion of the goodness-of-fit for the optimized subsite map. The application of the minimization procedure to subsite mapping is explored through the use of simulated data. A procedure is developed whereby the minimization model can be used to determine the number of subsites in the enzymic binding region and to locate the position of the catalytic amino acids among these subsites. The degree of propagation of experimental variance into the subsite-binding energies is estimated. The question of whether hydrolytic rate coefficients are constant or a function of the number of filled subsites is examined.     

A model for the competitive growth of two diatoms

A parallel between an experimental situation in marine microecology and its analytical model is presented. Two diatoms are cultured in a continuous flow apparatus and are studied for their competitive performance. A differential equations model is proposed to represent their growth behavior. The parameters of the model are evaluated from the experimental data and it is then identified from additional data.     

A simplified model of scar contraction

The healing of wounds is a complex process and the contraction of the resulting scar can have a negative impact on the neighbouring skin. A finite element model of skin simulating the contraction of a scar and deformation of the surrounding skin is presented. The skin is represented by an orthotropic–viscoelastic constitutive law, which is validated against experimental data in the literature. A simplified experimental model of a contracting scar in real skin is also developed. The pattern and size of the wrinkles formed around the contracting scar in the finite element model compare favourably with those formed in the experimental model. The orthotropic nature of skin plays a significant role in the behaviour of skin around scars—the wrinkles have a preferential orientation that corresponds to a direction perpendicular to the Langer's lines in the skin. The pre-stress in skin (a property that is ignored in many skin models) is shown to be an important factor in wrinkle formation around scars. The proposed model can be used to analyse the suturing and closure of wounds of various shapes.     

Correlation between the osmotic second virial coefficient and the solubility of proteins

A correlation between the osmotic second virial coefficient and the solubility of proteins is derived from classical thermodynamics to support an empirical relation previously found by Wilson and co-workers (1). The model is based on the equality of fugacities of the protein in the equilibrium phases, with the details of the model depending on the standard state used. The parameters in this model have been fitted to data for several systems, mainly with lysozyme as the protein. The model is found to describe experimental data, with variations in protein concentration, salt type and concentration, temperature, and pH, both qualitatively and quantitatively. Agreement between the model and the experimental data is very good for protein solubilities up to 30 mg/mL. Above this value the model underpredicts the experimental data, probably as a result of multibody interactions that are not included in the model here. Variations of the model parameters with protein type, temperature, pH, and salt type are discussed.     

Construction of rat spinal cord injury model based on Allen’s animal model

The aim of this study is to explore the construction of rat spinal cord injury model guided by Allen's model. Methods: Male rats aged 4–5 weeks and weighing about 250 g are selected as subjects in the Animal Laboratory Center of XX Hospital. Rats are divided into two groups, which are experimental group 1 and experimental group 2, respectively, so as to construct spinal cord injury model in rats. The first group is given 300 g.cm hitting force of T10 spinal cord, and the second group is given 500 g.cm hitting force of T10 spinal cord. Within 25 days after spinal cord injury in Allen's rats, the survival, neurological function, diet, motor ability, tactile ability and auditory ability of the two groups are monitored and evaluated daily. Results: In terms of survival, the survival rate of rats in group 1 is 85%, while that of rats in group 2 is 21%, and there is a concentrated death phenomenon in group 2. In terms of neurological function recovery, experimental group 1 is stable and gets 7 points and experimental group 2 is stable and gets 3 points. In terms of diet, the experimental group 1 is stable and gets 5 points and the experimental group 2 is stable and gets 2 points. In terms of motor ability, the experimental group 1 is stable and gets 5 points and the experimental group 2 is stable and gets 2 points. In tactile sense, experimental group 1 is stable and gets 17 points and experimental group 2 is stable and gets 12 points. It can be seen that the post-operative recovery ability of the experimental group 1 is better than that of the experimental group 2. Conclusion: Under the guidance of Allen's model, compared with the group 2, the experimental group 1 of the rat spinal cord injury model has better recovery in each index. It can be seen that the smaller impact strength is more beneficial to the recovery of rats after spinal cord injury surgery.     

A statistical mechanical treatment of fatty acyl chain order in phospholipid bilayers and correlation with experimental data. B. Dipalmitoyl-3-sn-phosphatidylcholine

In order to help bridge the conceptual gap between experimental data on chains of phospholipid molecules and their microscopic organization, a theoretical model has been proposed in a preceding paper. The intentions associated with the new theory were to describe a model able to reproduce accurately the experimental data. This capability is essential to monitor some of the mechanisms behind the physical data. The results presented here show first that, provided a suitable fitting of the phenomenological parameters entailed in the model, the theory indeed gives good agreement with experimental data (²H-NMR, neutron scattering, calorimetry) obtained for a $\text{dipalmitoyl}\text{-3-sn-}\text{phosphatidylcholine}$ bilayer. This property of the model is then specifically used to describe the nature of the perturbing effects of local anaesthetics and cholesterol on the organization of the acyl chains and to correlate these effects with the experimental data. Finally the theoretical model is used to supplement experimental data by describing the acyl chain organization in terms of the most probable spectrum of chain conformations. Predictions are made about the one-, two- and three-dimensional mean spatial characteristics of the acyl chains.     

A differential adhesion approach to the patterning of nerve connections

A model for the ordering of neuronal connections encompassing many facets of previous models is developed and tested against a wide range of data on the visual system of lower vertebrates (amphibia and fish). The goal of this paper is to establish that such a synthetic model can accommodate a wide range of data and reliably predict experimental results. This model makes two advances over previous efforts: (i) It predicts both minority and majority results for many of the experiments in which mixed results are obtained, and (ii) it reduces to behave as many of the previous models in some experimental settings. In addition, the model predicts different biochemical properties for cell-cell recognition than previously considered (i.e., homophilic adhesion). The model thus brings apparently disparate experimental results into a unified conceptual framework.     

Activity Variants of Acid Phosphatase-3 among Chromosome 3 Inversions of DROSOPHILA PSEUDOOBSCURA

Sexual selection is measured between two strains of Drosophila melanogaster: a wild strain and a strain mutant at the sepia locus. Frequency-dependent male mating was found to be successful, whereas the female genotype exerted no influence. The rarer the male genotype becomes, the greater is its mating success. A selection model is built for this behavior characteristic in which selection operates differently in the two sexes. The genetic consequencies of this model upon the maintenance of genetic polymorphism at the sepia locus are compared to experimental data from previous population cage studies. The fit obtained with this sexual selection model is compared to that of the larvel selection model previously investigated. A model composed of both sexual and larval components of fitness is presented. The role that each major selection component is expected to play in experimental populations as the gene frequency changes is discussed. Sexual selection leads to an equilibrium level higher than larval selection, and the combined model is very close to the experimental values.     

基于多次重复液相质谱生物实验数据校准方法研究

在蛋白质组学中,进行液相质谱(LC-MS)实验谱数据处理,发现并分析生物标志物的复杂肽或蛋白质样本的差异是重点,而校准相同样本的多次重复实验中肽链产生的洗脱时间峰信号(LC峰)是进行量化、分析差异的关键。目前多个重复实验数据的校准通常是在重复的实验数据集中根据液相二级质谱(LC-MS/MS)实验标识LC峰的时间特征,然后使用翘曲函数对时间特征进行对齐。由于多重数据的洗脱时间误差产生是随机的,统一使用翘曲函数校准会产生较大误差。为了解决这个问题,本研究重点研究了多个重复实验数据中LC峰的时间校准算法。我们选取了两个重复实验数据,采用机器学习的思路,通过选用两个数据的LC-MS/MS中重复检测到的肽链数据作为可信数据,部分选为训练序列,部分作为测试序列,建立统计数学模型,提出了一种新的校准算法,并采用测试序列对该统计模型进行准确率测试,表明算法的准确性达到95%以上;然后,将该模型应用在两个实验数据的所有LC-MS/MS肽链检测值上,提高检测值在多个数据中的覆盖率,表明覆盖率可以到达85%以上。     

A simple model describing nitrate and nitrite reduction in fluidized bed biological reactors

A uniquely simple model is developed to describe the NO(3) (-) and NO(2) (-) concentration profiles within a dentrification fluidized bed biological reactor. This simple model is compared to experimental data, and to a more complex model similar to those previously proposed in the literature. The simple model fits the experimental data at least as well as the more complex model. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 543-548, 1997.     

分子实验技能课程教学模式初探

目的:探索适合临床研究生的分子实验技能课教学模式,提高研究生科研思维能力和实验技能。方法:根据临床研究生的特点,以学生为主体,注重学生科研思维的培养,运用多样化的教学手段,对研究生临床分子实验技能课程的教学方法进行探索。结果:通过实验技能课的学习与培训,临床研究生科研思维能力得到很大的提升,对医学实验研究兴趣增加,取得了很好的教学效果。结论:多元化教学模式比较适合临床研究生实验技能课的教学。