Docking and molecular dynamics simulation of quinone compounds with trypanocidal activity

In this work, two different docking programs were used, AutoDock and FlexX, which use different types of scoring functions and searching methods. The docking poses of all quinone compounds studied stayed in the same region in the trypanothione reductase. This region is a hydrophobic pocket near to Phe396, Pro398 and Leu399 amino acid residues. The compounds studied displays a higher affinity in trypanothione reductase (TR) than glutathione reductase (GR), since only two out of 28 quinone compounds presented more favorable docking energy in the site of human enzyme. The interaction of quinone compounds with the TR enzyme is in agreement with other studies, which showed different binding sites from the ones formed by cysteines 52 and 58. To verify the results obtained by docking, we carried out a molecular dynamics simulation with the compounds that presented the highest and lowest docking energies. The results showed that the root mean square deviation (RMSD) between the initial and final pose were very small. In addition, the hydrogen bond pattern was conserved along the simulation. In the parasite enzyme, the amino acid residues Leu399, Met400 and Lys402 are replaced in the human enzyme by Met406, Tyr407 and Ala409, respectively. In view of the fact that Leu399 is an amino acid of the Z site, this difference could be explored to design selective inhibitors of TR.

Using system dynamics for collaborative design : a case study

Background  In order to facilitate the collaborative design, system dynamics (SD) with a group modelling approach was used in the early stages of planning a new stroke unit. During six workshops a SD model was created in a multiprofessional group. Aim To explore to which extent and how the use of system dynamics contributed to the collaborative design process. Method A case study was conducted using several data sources. Results SD supported a collaborative design, by facilitating an explicit description of stroke care process, a dialogue and a joint understanding. The construction of the model obliged the group to conceptualise the stroke care and experimentation with the model gave the opportunity to reflect on care. Conclusion SD facilitated the collaborative design process and should be integrated in the early stages of the design process as a quality improvement tool.

The behaviour of US stock prices : evidence from a threshold autoregressive model

This paper investigates the behaviour of US stock prices using an unrestricted two-regime threshold autoregressive (TAR) model with an autoregressive unit root. The TAR model is applied to monthly stock price (NYSE Common Stocks) data for the US for the period 1964:06 to 2003:04. Amongst our main results, we find that the US stock price is a nonlinear series that is characterized by a unit root process, consistent with the efficient market hypothesis.

An agent-based approach to value theory and wealth distribution in economics

Any attempt to model an economy requires foundational assumptions about the relations between prices, values and the distribution of wealth. These assumptions exert a profound influence over the results of any model. Unfortunately, there are few areas in economics as vexed as the theory of value. I argue in this paper that the fundamental problem with past theories of value is that it is simply not possible to model the determination of value, the formation of prices and the distribution of income in a real economy with analytic mathematical models. All such attempts leave out crucial processes or make unrealistic assumptions which significantly affect the results. There have been two primary approaches to the theory of value. The first, associated with classical economists such as Ricardo and Marx were substance theories of value, which view value as a substance inherent in an object and which is conserved in exchange. For Marxists, the value of a commodity derives solely from the value of the labour power used to produce it - and therefore any profit is due to the exploitation of the workers. The labour theory of value has been discredited because of its assumption that labour was the only ‘factor’ that contributed to the creation of value, and because of its fundamentally circular argument. Neoclassical theorists argued that price was identical with value and was determined purely by the interaction of supply and demand. Value then, was completely subjective. Returns to labour (wages) and capital (profits) were determined solely by their marginal contribution to production, so that each factor received its just reward by definition. Problems with the neoclassical approach include assumptions concerning representative agents, perfect competition, perfect and costless information and contract enforcement, complete markets for credit and risk, aggregate production functions and infinite, smooth substitution between factors, distribution according to marginal products, firms always on the production possibility frontier and firms’ pricing decisions, ignoring money and credit, and perfectly rational agents with infinite computational capacity. Two critical areas include firstly, the underappreciated Sonnenschein-Mantel- Debreu results which showed that the foundational assumptions of the Walrasian general-equilibrium model imply arbitrary excess demand functions and therefore arbitrary equilibrium price sets. Secondly, in real economies, there is no equilibrium, only continuous change. Equilibrium is never reached because of constant changes in preferences and tastes; technological and organisational innovations; discoveries of new resources and new markets; inaccurate and evolving expectations of businesses, consumers, governments and speculators; changing demand for credit; the entry and exit of firms; the birth, learning, and death of citizens; changes in laws and government policies; imperfect information; generalized increasing returns to scale; random acts of impulse; weather and climate events; changes in disease patterns, and so on. The problem is not the use of mathematical modelling, but the kind of mathematical modelling used. Agent-based models (ABMs), objectoriented programming and greatly increased computer power however, are opening up a new frontier. Here a dynamic bargaining ABM is outlined as a basis for an alternative theory of value. A large but finite number of heterogeneous commodities and agents with differing degrees of market power are set in a spatial network. Returns to buyers and sellers are decided at each step in the value chain, and in each factor market, through the process of bargaining. Market power and its potential abuse against the poor and vulnerable are fundamental to how the bargaining dynamics play out. Ethics therefore lie at the very heart of economic analysis, the determination of prices and the distribution of wealth. The neoclassicals are right then that price is the enumeration of value at a particular time and place, but wrong to downplay the critical roles of bargaining, power and ethics in determining those same prices.

A full body musculoskeletal model based on flexible multibody simulation approach utilised in bone strain analysis during human locomotion

Load-induced strains applied to bone can stimulate its development and adaptation. In order to quantify the incident strains within the skeleton, in vivo implementation of strain gauges on the surfaces of bone is typically used. However, in vivo strain measurements require invasive methodology that is challenging and limited to certain regions of superficial bones only such as the anterior surface of the tibia. Based on our previous study [Al Nazer et al. (2008) J Biomech. 41:1036–1043], an alternative numerical approach to analyse in vivo strains based on the flexible multibody simulation approach was proposed. The purpose of this study was to extend the idea of using the flexible multibody approach in the analysis of bone strains during physical activity through integrating the magnetic resonance imaging (MRI) technique within the framework. In order to investigate the reliability and validity of the proposed approach, a three-dimensional full body musculoskeletal model with a flexible tibia was used as a demonstration example. The model was used in a forward dynamics simulation in order to predict the tibial strains during walking on a level exercise. The flexible tibial model was developed using the actual geometry of human tibia, which was obtained from three-dimensional reconstruction of MRI. Motion capture data obtained from walking at constant velocity were used to drive the model during the inverse dynamics simulation in order to teach the muscles to reproduce the motion in the forward dynamics simulation. Based on the agreement between the literature-based in vivo strain measurements and the simulated strain results, it can be concluded that the flexible multibody approach enables reasonable predictions of bone strain in response to dynamic loading. The information obtained from the present approach can be useful in clinical applications including devising exercises to prevent bone fragility or to accelerate fracture healing.

High glucose-induced impairment in insulin secretion is associated with reduction in islet glucokinase in a mouse model of susceptibility to islet dysfunction

Type 2 diabetes is characterized by islet dysfunction resulting in hyperglycemia, which can then lead to further deterioration in islet function. A possible mechanism for hyperglycemia-induced islet dysfunction is the accumulation of advanced glycation end products (AGE). The DBA/2 mouse develops pancreatic islet dysfunction when exposed to a high glucose environment and/or obesity-induced insulin resistance. To determine the biochemical cause of dysfunction, DBA/2 and C57BL/6 control islets were incubated in 11.1 mM or 40 mM glucose in the absence or presence of the AGE inhibitor aminoguanidine (AG) for 10 days. Basal (2.8 mM glucose) insulin release was increased in both DBA/2 and C57BL/6 islets incubated with 40 mM vs 11.1 mM glucose for 10 days. Chronic exposure to hyperglycemia decreased glucose (20 mM)-stimulated insulin secretion in DBA/2 but not in C57BL/6 islets. AG significantly increased fold-induced insulin release in high glucose cultured DBA/2 mouse islets, but did not affect C57BL/6 islet function. DBA/2 islet glucokinase was significantly reduced following 40 mM glucose culture, compared with 11.1 mM glucose cultured DBA/2 islets and 40 mM glucose cultured C57BL/6 islets. Incubation of islets with AG resulted in a normalization of DBA/2 islet glucokinase levels. In conclusion, chronic high glucose-induced increases in AGE can result in islet dysfunction and this is associated with reduced glucokinase levels in a mouse model with susceptibility to islet failure.

Modeling propagation dynamics of social network worms

Social network worms, such as email worms and facebook worms, pose a critical security threat to the Internet. Modeling their propagation dynamics is essential to predict their potential damages and develop countermeasures. Although several analytical models have been proposed for modeling propagation dynamics of social network worms, there are two critical problems unsolved: temporal dynamics and spatial dependence. First, previous models have not taken into account the different time periods of Internet users checking emails or social messages, namely, temporal dynamics. Second, the problem of spatial dependence results from the improper assumption that the states of neighboring nodes are independent. These two problems seriously affect the accuracy of the previous analytical models. To address these two problems, we propose a novel analytical model. This model implements a spatial-temporal synchronization process, which is able to capture the temporal dynamics. Additionally, we find the essence of spatial dependence is the spreading cycles. By eliminating the effect of these cycles, our model overcomes the computational challenge of spatial dependence and provides a stronger approximation to the propagation dynamics. To evaluate our susceptible-infectious-immunized (SII) model, we conduct both theoretical analysis and extensive simulations. Compared with previous epidemic models and the spatial-temporal model, the experimental results show our SII model achieves a greater accuracy. We also compare our model with the susceptible-infectious-susceptible and susceptible-infectious- recovered models. The results show that our model is more suitable for modeling the propagation of social network worms.

A panel error correction approach to explore spatial correlation patterns of the dominant housing market in Australian capital cities

Purpose - A panel error correction model has been developed to investigate the spatial correlation patterns among house prices. This paper aims to identify a dominant housing market in the ripple down process. Design/methodology/approach - Seemingly unrelated regression estimators are adapted to deal with the contemporary correlations and heterogeneity across cities. Impulse response functions are subsequently implemented to simulate the spatial correlation patterns. The newly developed approach is then applied to the Australian capital city house price indices. Findings - The results suggest that Melbourne should be recognised as the dominant housing market. Four levels were classified within the Australian house price interconnections, namely: Melbourne; Adelaide, Canberra, Perth and Sydney; Brisbane and Hobart; and Darwin. Originality/value - This research develops a panel regression framework in addressing the spatial correlation patterns of house prices across cities. The ripple-down process of house price dynamics across cities was explored by capturing both the contemporary correlations and heterogeneity, and by identifying the dominant housing market.

A mathematical model for the spread of streptococcus pneumoniae with transmission due to sequence type

This paper discusses a simple mathematical model to describe the spread of Streptococcus pneumoniae. We suppose that the transmission of the bacterium is determined by multi-locus sequence type. The model includes vaccination and is designed to examine what happens in a vaccinated population if MLSTs can exist as both vaccine and non vaccine serotypes with capsular switching possible from the former to the latter. We start off with a discussion of Streptococcus pneumoniae and a review of previous work. We propose a simple mathematical model with two sequence types and then perform an equilibrium and (global) stability analysis on the model. We show that in general there are only three equilibria, the carriage-free equilibrium and two carriage equilibria. If the effective reproduction number Re is less than or equal to one, then the carriage will die out. If Re > 1, then the carriage will tend to the carriage equilibrium corresponding to the multi-locus sequence type with the largest transmission parameter. In the case where both multi-locus sequence types have the same transmission parameter then there is a line of carriage equilibria. Provided that carriage is initially present then as time progresses the carriage will approach a point on this line. The results generalize to many competing sequence types. Simulations with realistic parameter values confirm the analytical results.

A dynamic model of tourism, employment and welfare: the case of Hong Kong

The present paper uses a dynamic open-economy model with wage indexation to examine the impact of tourism on employment and welfare. Both short-run and long-run situations are analysed. It is well known that tourism converts non-traded goods into tradable goods. An increase in the demand for a non-traded good raises its relative price, which results in an expansion of the non-traded sector at the expense of the traded goods sector. This output shift raises labour employment in the short run. However, in the long run, the higher relative price leads to higher wages, resulting in a negative impact on labour employment. If the output effect is dominant, the expansion in tourism raises employment and welfare. However, under realistic conditions tourism may lower both labour employment and welfare due to rising costs. These results are demonstrated by simulating a dynamic model for the case of Hong Kong.

Paradigm shift to enhanced water supply planning through augmented grids, scarcity pricing and adaptive factory water : a system dynamics approach

This paper details a system dynamics model developed to simulate proposed changes to water governance through the integration of supply, demand and asset management processes. To effectively accomplish this, interconnected feedback loops in tariff structures, demand levels and financing capacity are included in the model design, representing the first comprehensive life-cycle modelling of potable water systems. A number of scenarios were applied to Australia's populated South-east Queensland region, demonstrating that introducing temporary drought pricing (i.e. progressive water prices set inverse with availability), in conjunction with supply augmentation through rain-independent sources, is capable of efficiently providing water security in the future. Modelling demonstrated that this alternative tariff structure reduced demand in scarcity periods thereby preserving supply, whilst revenues are maintained to build new water supply infrastructure. In addition to exploring alternative tariffs, the potential benefits of using adaptive pressure-retarded osmosis desalination plants for both potable water and power generation was explored. This operation of these plants for power production, when they would otherwise be idle, shows promise in reducing their net energy and carbon footprints. Stakeholders in industry, government and academia were engaged in model development and validation. The constructed model displays how water resource systems can be reorganised to cope with systemic change and uncertainty.

Non-homogeneous volatility correlations in the bivariate multifractal model

In this paper, we consider an extension of the recently proposed bivariate Markov-switching multifractal model of Calvet, Fisher, and Thompson [2006. "Volatility Comovement: A Multifrequency Approach." Journal of Econometrics {131}: 179-215]. In particular, we allow correlations between volatility components to be non-homogeneous with two different parameters governing the volatility correlations at high and low frequencies. Specification tests confirm the added explanatory value of this specification. In order to explore its practical performance, we apply the model for computing value-at-risk statistics for different classes of financial assets and compare the results with the baseline, homogeneous bivariate multifractal model and the bivariate DCC-GARCH of Engle [2002. "Dynamic Conditional Correlation: A Simple Class of Multivariate Generalized Autoregressive Conditional Heteroskedasticity Models." Journal of Business & Economic Statistics 20 (3): 339-350]. As it turns out, the multifractal model with heterogeneous volatility correlations provides more reliable results than both the homogeneous benchmark and the DCC-GARCH model. © 2014 Taylor & Francis.

Water security through scarcity pricing and reverse osmosis: a system dynamics approach

Water supply and demand planning is often conducted independently of social and economic strategies. There are presently no comprehensive life-cycle approaches to modelling urban water balances that incorporate economic feedbacks, such as tariff adjustment, which can in turn create a financing capacity for investment responses to low reservoir levels. This paper addresses this gap, and presents a system dynamics model that augments the usual water utility representation of the physical linkages of water grids, by adding inter-connected feedback loops in tariff structures, demand levels and financing capacity. The model, applied in the south-east Queensland region in Australia, enables simulation of alternatives and analysis of stocks and flows around a grid or portfolio of bulk supplies including an increasing proportion of rain-independent desalination plants. Such rain-independent water production plants complement the rain-dependent sources in the region and can potentially offer indefinite water security at a price. The study also shows how an alternative temporary drought pricing regime not only defers costly bulk supply infrastructure but actually generates greater price stability than traditional pricing approaches. The model has implications for water supply planners seeking to pro-actively plan, justify and finance portfolios of rain-dependent and rain-independent bulk water supply infrastructure. Interestingly, the modelling showed that a temporary drought pricing regime not only lowers the frequency and severity of water insecurity events but also reduces the long-run marginal cost of water supply for the region when compared to traditional reactive planning approaches that focus on restrictions to affect demand in scarcity periods.

Molecular dynamics study of response of liquid N,N-dimethylformamide to externally applied electric field using a polarizable force field

The behavior of Liquid N,N-dimethylformamide subjected to a wide range of externally applied electric fields (from 0.001 V/nm to 1 V/nm) has been investigated through molecular dynamics simulation. To approach the objective the AMOEBA polarizable force field was extended to include the interaction of the external electric field with atomic partial charges and the contribution to the atomic polarization. The simulation results were evaluated with quantum mechanical calculations. The results from the present force field for the liquid at normal conditions were compared with the experimental and molecular dynamics results with non-polarizable and other polarizable force fields. The uniform external electric fields of higher than 0.01 V/nm have a significant effect on the structure of the liquid, which exhibits a variation in numerous properties, including molecular polarization, local cluster structure, rotation, alignment, energetics, and bulk thermodynamic and structural properties.

Has oil price predicted stock returns for over a century?

This paper contributes to the debate on the role of oil prices in predicting stock returns. The novelty of the paper is that it considers monthly time-series historical data that span over 150. years (1859:10-2013:12) and applies a predictive regression model that accommodates three salient features of the data, namely, a persistent and endogenous oil price, and model heteroscedasticity. Three key findings are unraveled: first, oil price predicts US stock returns. Second, in-sample evidence is corroborated by out-sample evidence of predictability. Third, both positive and negative oil price changes are important predictors of US stock returns, with negative changes relatively more important. Our results are robust to the use of different estimators and choice of in-sample periods.