Slow equilibration of a denatured protein: comparison of the cluster model with the proline isomerization model

The slow equilibration of the denatured state after rapid unfolding of a globular protein is examined by the cluster model of protein folding (Kanehisa &; Tsong, 1978). The detection of this process in ribonuclease A and its acid catalysis have been considered evidence for the proline isomerization model. Our calculation shows that similar kinetic behavior is also expected for the cluster model.     

Lichtheim 2: synthesizing aphasia and the neural basis of language in a neurocomputational model of the dual dorsal-ventral language pathways

Traditional neurological models of language were based on a single neural pathway (the dorsal pathway underpinned by the arcuate fasciculus). Contemporary neuroscience indicates that anterior temporal regions and the "ventral" language pathway also make a significant contribution, yet there is no computationally-implemented model of the dual pathway, nor any synthesis of normal and aphasic behavior. The "Lichtheim 2" model was implemented by developing a new variety of computational model which reproduces and explains normal and patient data but also incorporates neuroanatomical information into its architecture. By bridging the "mind-brain" gap in this way, the resultant "neurocomputational" model provides a unique opportunity to explore the relationship between lesion location and behavioral deficits, and to provide a platform for simulating functional neuroimaging data.     

Difference equation model of the entrainment of myocardial pacemaker cells based on the phase response curve

As a method for investigating entrainment phenomena found in biological oscillations, a model is presented which is formulated as a set of difference equations on the basis of phase response curves of biological oscillators. Properties of the model are discussed and synchronization of cardiac pacemaker cells to the external periodic stimuli is analyzed by use of the model. It is shown that the model is reducible to an equivalent system to the mathematical neuron model of Nagumo et al. under a specific parametric condition of the phase response curve. As an application to the cardiac arrhythmias, the model of ventricular parasystoles studied by Moe et al. is described mathematically in terms of a system of difference equations. In addition, a more comprehensive model of ventricular parasystoles is proposed.     

Estimating the pattern of nucleotide substitution

Knowledge of the pattern of nucleotide substitution is important both to our understanding of molecular sequence evolution and to reliable estimation of phylogenetic relationships. The method of parsimony analysis, which has been used to estimate substitution patterns in real sequences, has serious drawbacks and leads to results difficult to interpret. In this paper a model-based maximum likelihood approach is proposed for estimating substitution patterns in real sequences. Nucleotide substitution is assumed to follow a homogeneous Markov process, and the general reversible process model (REV) and the unrestricted model without the reversibility assumption are used. These models are also applied to examine the adequacy of the model of Hasegawa et al. (J. Mol. Evol. 1985;22:160–174) (HKY85). Two data sets are analyzed. For the -globin pseudogenes of six primate species, the REV model fits the data much better than HKY85, while, for a segment of mtDNA sequences from nine primates, REV cannot provide a significantly better fit than HKY85 when rate variation over sites is taken into account in the models. It is concluded that the use of the REV model in phylogenetic analysis can be recommended, especially for large data sets or for sequences with extreme substitution patterns, while HKY85 may be expected to provide a good approximation. The use of the unrestricted model does not appear to be worthwhile.     

An automata-theoretical model of the vegetative and flowering development of Hieracium murorum L.

By means of a computer model certain essential aspects of the vegetative and flowering development of Hieracium murorum have been successfully simulated. The model is based on local control mechanisms operating over a large number of units and is stated in terms of the theory of developmental systems and languages. The model is constructed as a table deterministic 1,1 L-system. The model is especially concerned with the correlation mechanisms between the various differentiating parts of the plant.This work has been supported by a grant from the Netherlands Organization for the Advancement of Pure Research (Z.W.O.)     

Automatic search for model to simulate the differentiation of T lymphocytes within the thymus

The differentiation of T Lymphocytes within the thymus is an important biological phenomenon during wich these cell acquire their functions to further control the immune system. Numerous experiments under various conditions have been devised to understand the different mechanisms involved in this complex process. Nevertheless, interpretation of these experiments lead to still contradictory debatable hypotheses. Modelisation of this process through classical simulation methods cannot be envisaged because they are not adapted to modifications of the model structure, which is the point of interest. For these reasons, we proposed a new approach of automatic search for model. The program consists of four independent connected modules : The generator produces model, based on the rationale of formal grammars. Protocol and experimental data are stored in a set of experiments. The simulator using a protocol and a model provides simulated results. Finally, the supervisor by comparing simulated results and experimental data, adapts the model parameters to increase their fit and either chooses a new experiment to explore, or modifies the model structure. Change of the model structure is performed among still unexplored models according to their promise level, which is iteratively evaluated relatively to previously explored models through a proposed model distance. The generator is written in Prolog and the other modules in C++. The architecture of the program allows us to modify or complete a module without changing anything in the other modules. As a consequence, the proposed modeling approach conceived to study T lymphocyte differentiation within the thymus remains independent of this biological phenomenon and can be applied to other biological problems.     

A mathematical model for the growth of the abdominal aortic aneurysm

We present the first mathematical model to account for the evolution of the abdominal aortic aneurysm. The artery is modelled as a two-layered, cylindrical membrane using nonlinear elasticity and a physiologically realistic constitutive model. It is subject to a constant systolic pressure and a physiological axial prestretch. The development of the aneurysm is assumed to be a consequence of the remodelling of its material constituents. Microstructural recruitment and fibre density variables for the collagen are introduced into the strain energy density functions. This enables the remodelling of collagen to be addressed as the aneurysm enlarges. An axisymmetric aneurysm, with axisymmetric degradation of elastin and linear differential equations for the remodelling of the fibre variables, is simulated numerically. Using physiologically determined parameters to model the abdominal aorta and realistic remodelling rates for its constituents, the predicted dilations of the aneurysm are consistent with those observed in vivo. An asymmetric aneurysm with spinal contact is also modelled, and the stress distributions are consistent with previous studies.     

Demographic consequences of genetic load: a model of the origin of the incest taboo

The prohibition of copulations among near relatives may raise the fitness of population. This effect being irregular and insignificant for a distinct generation, becomes apparent in evolutionary time intervals through the natural selection of populations with incest-taboo. The "characteristic selection time" theta depends on typical population size, genetic damage and the mean rate of population growth. The estimation obtained for theta permit us to assert that the model describes the phenomenon of "socio-cultural selection" in prehistory. The model shows the demographic specificity of small populations. The problem of the number of consanguineous marriages is considered in detail. New explanation for deviation of the observed frequency of consanguineous marriages from classical estimations is proposed.     

Mouse Model of Muscle Crush Injury of the Legs

Because crush injury to skeletal muscle is an important cause of morbidity in natural disaster and battlefield settings, a reproducible and refined animal model of muscle crush injury is needed. Both open and closed small-animal models of skeletal muscle crush injury are available but are limited by their need for surgical isolation of the muscle or by the adverse effect of fibular fracture, respectively. In the current study, we developed and validated a novel, noninvasive mouse model of lower-extremity muscle crush injury. Despite the closed nature of our model, gross evidence of muscle damage was evident in all mice and was verified microscopically through hematoxylin and eosin staining. The injury elicited both neutrophil and macrophage infiltration at 24 and 48 h after injury. The area percentage and mean antigen area of F4/80-positive macrophages were higher at 48 h than at 24 h after injury, and CD68-positive macrophage area percentage and mean antigen area differed significantly between injured and uninjured muscle. In addition, the incidence of fibular fracture was one third lower than that reported for an alternative noninvasive model. In conclusion, our model is a reproducible method for muscle crush injury in the mouse pelvic limb and is a refinement of previous models because of its decreased bone fractures and reduction of animal numbers.Abbreviations: AOI, area of interestSkeletal muscle crush injury is an important cause of morbidity in both civilian and military populations. During earthquakes, tornados, and other natural disasters, collapsed structures result in crush injuries in approximately 40% of victims entrapped in the rubble,¹⁴ and crush injuries sustained during these events primarily affect skeletal muscle tissue.¹³ Crush injuries to skeletal muscle received during military conflict can occur when a limb is compressed for an extended time period, and combat-related crush injuries of the extremities frequently are present in wounded troops who are transported via aeromedical evacuation.²²A muscle-crush injury is induced when pressure is applied to skeletal muscle, interrupting blood flow and damaging the cell membranes of the muscle fibers. Several animal models of skeletal muscle-crush injury are used to study the pathophysiology of acute muscle inflammation and to investigate potential therapies.^{1,2,3,5,8,9,12,17,18,21} The most common model is the application of force to a surgically isolated pelvic limb muscle by using a clamp.¹⁶ Although closed models have been investigated, these studies typically involve dropping weights onto rodents’ pelvic limbs, thereby increasing the adverse event of fractures. Although not often reported in the literature, the incidence of fibular fractures in rats as a result of the dropped weight was 27% in one study.³ An additional drawback to the dropped-weight model is that it simulates a high-force contusion injury and does not provide the ischemic effect of the continuous pressure applied by the open clamp model. The ideal crush-injury model would mimic a force-induced injury, because 40% of survivors trapped in building rubble develop ischemia-induced crush syndrome.¹⁴We chose to investigate a novel model of closed crush injury for several reasons. An animal model of skeletal muscle injury should mimic the human clinical presentation, and a closed model more closely simulates a real-world crush injury. Second, because the incision created in the open model can activate the inflammatory response, a group of sham-operated animals is needed to control for the variable of the incision-induced inflammation. By using a closed model, the contralateral limb can serve as the uninjured control, thereby reducing the number of animals needed to perform the study. Last, the closed model represents a refinement of the crush injury procedure by removing the additional tissue damage and inflammation that result from the incision and tissue dissection of the surgical procedure and by reducing the incidence of fractures.Because this model has not been described in the literature, the objective of the current study was to develop a closed, sustained-force model of lower-extremity crush injury that induces a measurable leukocyte response and minimizes damage to nearby bones. In addition, we used monoclonal antibodies to characterize the leukocyte populations associated with this skeletal muscle crush injury model.     

Quantum-mechanical kinetic study of the primary reaction of the photochemical cycle of Halobacterium halobium

A two-frequency oscillator model for the primary photochemical reaction bacteriorhodopsin batho-bacteriorhodopsin (K₆₁₀) is proposed. According to this model two conformational changes in the reaction are considered to take place: the first one is a distortion of the retinal in the bacteriorhodopsin active site and the second one is a conformational transition of the bacterioopsin, affecting the native structure hydrogen bonds. On the basis of this model the temperature dependences of the rate constants for normal and deuterated reactants are calculated in good agreement with the available experimental data. The relations of the reaction considered to the primary photochemical reaction of vision are discussed.     

Simulating the role of microtubules in depolymerization-driven transport: a Monte Carlo approach.

In this paper we present a model that simulates the role of microtubules in depolymerization-driven transport. The model simulates a system that consists of a 13-protofilament microtubule with "five-start" helical structure and a motor protein-coated bead that moves along one of the protofilaments of the microtubule, as in in vitro experiments. The microtubule is simulated using the lateral cap model, with substantial generalizations. For the new terminal configurations in the presence of the bead, rate constants for association and dissociation events of tubulin molecules are calculated by exploring the geometric similarities between different patterns of terminal configurations and by decomposing complex patterns into simpler patterns whose corresponding rate constants are known. In comparison with a previous model, in which simplifications are made about the structure of the microtubule and in which the microtubule can only depolymerize, the detailed structure of the microtubule is taken into account in the present model. Furthermore, the microtubule can be either polymerizing or depolymerizing. Force-velocity curves are obtained for both zero and non-zero tubulin guanosine 5'-triphosphate (GTP) concentrations. By analyzing the trajectory of the bead under different parameters, the condition for "run and pause" is analyzed, and the time scale of "run" and "pause" is found to be different for different motor proteins. We also suggest experiments that can be used to examine the results predicted by the model.     

Self-organization of the velocity selectivity of a directionally selective neural network

We first present a mathematical analysis of the relation between the parameters and the behavior of the basic module in the proposed neural network model for visual motion detection. Based on the analytical results, a learning rule is put forth that can develop velocity selectivity of directionally selective cells in the basic module. The learning rule is furthermore introduced into the total model called a mass model, which is constructed with many basic modules. Numerical simulation results showed that each basic module in the mass model learned in a self-organizing manner to acquire selectivity for the velocity of an input stimulus. The proposed learning rule would be plausible in the actual nervous system in that it is simple and can be described with only local information.     

Variance of genetic distance and correlation of heterozygosity between populations under the pressure of stepwise mutation

Using the stepwise mutation model of Ohta and Kimura (1973), formulas are developed for the correlation of heterozygosity and the variance of genetic distance between two finite populations. Studied in detail is the case where the sizes of the two descendant populations are equal to that of the ancestral population and the mutation rate is the same for all loci. Numerical computations are carried out by using the present formulas and those of Li and Nei (1975Genet. Res.25) for the infinite-allele model. The results are as follows: The correlation of heterozygosity decreases with time faster for the stepwise mutation model than for the infinite-allele model. However, the relationships between the correlation of heterozygosity and the normalized genetic identity for the two models are very similar, if the average heterozygosities of the two populations are around 0.20 or less. On the other hand, the variance of genetic distance for the stepwise mutation model may become considerably smaller than that for the infinite-allele model, if the average heterozygosities of the two populations are larger than 0.05. The ratio of the standard deviation to the mean is, however, very large for the stepwise mutation model as well as the infinite-allele model.     

Competition in the gradostat: the role of the communication rate

In this paper we study a mathematical model of competition between two species of microorganisms for a single limiting nutrient in a laboratory device called a gradostat. A gradostat consists of several (we consider only two) chemostats (CSTR's) connected together so that material can flow between the vessels in such a way that a nutrient gradient is established. Our model is a slightly modified version of one considered recently by Jäger et al. [3], in that the rate of exchange of material between the two vessels (the communication rate) is allowed to differ from the dilution rate. The outcome of competition turns out to be surprisingly sensitive to variation of the communication rate. We identify several coexistence regimes in parameter space and describe a method for obtaining operating diagrams for given pairs of competing microorganisms.Research supported in part by NSF Grant DMS 8521605     

基于CVM的海涂湿地生态服务价值的模糊评估模型

正确评估海涂湿地生态服务价值有助于加强人们保护海涂湿地的意识,为海涂湿地围垦生态补偿标准的制定提供依据。视价格"便宜"、"适中"和"昂贵"为模糊集,基于CVM法区间型数据建立了传统模糊统计模型、赋权模糊统计模型和三相划分模型,并以此评价了杭州湾国家湿地公园单位面积年生态系统服务价值。结果显示:3种方法得到的单价分别为10.28、10.38、9.76元m~(-2)a~(-1),三者一致程度较高,与国内沿海湿地价值比较接近。分析了"生态价值"概念客观上的"模糊性"引致模糊数学模型的合理性;采用"橄榄球"式赋权建立赋权模糊统计模型以克服传统模糊统计模型中对区间数据均匀赋权的不合理性,结果在隶属度函数的光滑性和拟合度上好于后者;第三,三相划分模型拟合出3个模糊集的隶属度函数,可以比较相同价格在不同模糊集中隶属度差异。建立的模型对于基于CVM法的生态资源价值评估具有借鉴意义。     

Asymptotic solution of the model of the erythrocyte shape as an autowave process

An asymptotic solution was plotted for a model of erythrocyte forms assuming that the biomembrane is anisotropic and of "small" thickness. This leads to small non-linearity and low diffusion, therefore the solution is unrelaxational. The model was investigated qualitatively assuming that the liquid current directed inside the spheric membrane induces its "distension", while that directed outside-its "crumpling". In the spherical system of coordinates the lines of solution level at theta = const are circumferences, while at phi-const-trochoids (Pascal coil, for example). Trochoids rotation areas show stomacyte and discocyte forms. Several hypotheses based on the analysis performed are advanced.     

Kinetic analysis of the chemotaxis of bacteria

On the basis of a kinetic model of bacterial chemotactic movement the system of differential equations was reduced to describe the phenomenon of bacterial bonds migration. It follows that Keller-Segel equation is a private case of a more general "diffusion approximation" of the kinetic model. The functional parameters of the reduced equation for E. coli K-12 are estimated.     

A linear stochastic model of the single motor unit

The production of force and of the electrical signal by an active motor unit is theoretically described. Neural spikes are modelled using the Dirac delta function. Mechanisms for the generation of random impulse trains and the properties of the corresponding stochastic processes are discussed; the renewal model is proposed as the most appropriate. The possibility of using a linear model for the systems that produce force and electrical signal in the unit is examined. It is concluded that the linear assumption is justifiable during steady, constant-strength contractions of muscle. This linear stochastic model of the motor unit is used in two subsequent papers to study the muscle force and the electromyogram.     

Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability

Background

Gut microbiota interacts with the human gut in multiple ways. Microbiota composition is altered in inflamed gut conditions. Likewise, certain microbial fermentation products as well as the lipopolysaccharides of the outer membrane are examples of microbial products with opposing influences on gut epithelium inflammation status. This system of intricate interactions is known to play a core role in human gut inflammatory diseases. Here, we present and analyse a simplified model of bidirectional interaction between the microbiota and the host: in focus is butyrate as an example for a bacterial fermentation product with anti-inflammatory properties.

Results

We build a dynamical model based on an existing model of inflammatory regulation in gut epithelial cells. Our model introduces both butyrate as a bacterial product which counteracts inflammation, as well as bacterial LPS as a pro-inflammatory bacterial product. Moreover, we propose an extension of this model that also includes a feedback interaction towards bacterial composition. The analysis of these dynamical models shows robust bi-stability driven by butyrate concentrations in the gut. The extended model hints towards a further possible enforcement of the observed bi-stability via alteration of gut bacterial composition. A theoretical perspective on the stability of the described switch-like character is discussed.

Conclusions

Interpreting the results of this qualitative model allows formulating hypotheses about the switch-like character of inflammatory regulation in the gut epithelium, involving bacterial products as constitutive parts of the system. We also speculate about possible explanations for observed bimodal distributions in bacterial compositions in the human gut. The switch-like behaviour of the system proved to be mostly independent of parameter choices. Further implications of the qualitative character of our modeling approach for the robustness of the proposed hypotheses are discussed, as well as the pronounced role of butyrate compared to other inflammatory regulators, especially LPS, NF- κB and cytokines.

     

Environmental impacts of the rental business model compared to the conventional business model: a Korean case of water purifier for home use

Purpose

This paper compares environmental impacts of the rental business model with the conventional model of manufacturing and selling. The case study examines a home use-water purifier by defining scenarios for operation and maintenance of the conventional and rental business models. Another purpose is to explore the potential improvement for the environmental performance of the rental business model in terms of the resource consumption and climate change.

Methods

The functional unit was supplying hot/cold drinking water for 15 years between 1998 and 2013. Primary data were from a Korean company that manufactures and servicizes water purifier; secondary data were from the Korean national LCI database, literatures, and interviews. Scenarios associated with all life cycle stages of a water purifier including operation and maintenance were based on current sales and rental market. Impact assessments were conducted according to the International Organization for Standardization’s 14044, and impact categories considered were global warming and abiotic resource depletion. The key issues and improvement potential of the rental business model were determined with the impact categories of global warming and abiotic resource depletion.

Results and discussion

This study indicates that the rental business model is more environmentally friendly than the conventional model in the impact on global warming while the conventional model shows lower abiotic resource depletion. Product operation was the most significant contributor to the selected environmental impacts for both conventional and rental models. Product maintenance was the second major contributor for the rental business model in terms of abiotic resource depletion. For the conventional model, however, production was a more significant contributor to the selected environmental impacts. The rental model showed approximately 32~37% improvements in the selected environmental impacts by focusing on the environmental education or information to consumers.

Conclusions

This quantitative life cycle assessment can be a tool for service business providers to understand the life cycle environmental impacts of Korean water purifier and explore potential improvement opportunities for sustainability. The lower life cycle impacts of the water purifier-rental business model can be attributed to the following: the preparation of instruction or environmental education regarding the consumer’s turning off behavior when the product is not in use, thus lower energy consumption during the use stage and shorter distance traveled for maintenance.