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Nonlocal interactions, which have attracted attention in various fields, result from the integration of microscopic information such as a transition possibility, molecular events, and signaling networks of living creatures. Nonlocal interactions are useful to reproduce various patterns corresponding to such detailed microscopic information. However, the approach is inconvenient for observing the specific mechanisms behind the target phenomena because of the compression of the information. Therefore, we previously proposed a method capable of approximating any nonlocal interactions by a reaction-diffusion system with auxiliary factors (Ninomiya et al., J Math Biol 75:1203-1233, 2017). In this paper, we provide an explicit method for determining the parameters of the reaction-diffusion system for the given kernel shape by using Jacobi polynomials under appropriate assumptions. We additionally introduce a numerical method to specify the parameters of the reaction-diffusion system with the general diffusion coefficients by the Tikhonov regularization. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a mathematical model for age-structured forest-beetle interactions that includes harvesting of trees. The aim is to broaden the understanding of the synergistic effects of harvesting and insect infestation on the age structure of the forests and the harvesting benefit. In the first part of this study, we consider different scenarios of the forest infestation by beetles and observe that the quantitative age profile of the forest depends significantly on whether the beetle population is in its endemic or epidemic states. In the second part, we also include harvesting of the forest trees and analyze two different harvesting strategies: cutting all trees older than a certain age, and cutting a fixed proportion of trees older than a certain age. Numerical simulations are implemented to determine the optimal cutting age for both harvesting strategies. The numerical simulations reveal that, independent of the steady state of the beetle population (that is, no beetles, endemic or epidemic state) clear cutting all trees older than a given age provides a higher harvesting benefit. Our numerical simulations further indicate that to obtain a fixed harvesting yield, a forest under a beetle epidemic state has to be cut at a younger age than if the forest were at an endemic beetle state or a no-beetle state. [ABSTRACT FROM AUTHOR]

This paper proposes a differential equation model of the human vision system. Our model has a hierarchical structure in the known retinal cell neural network, and hence, enable to explain what aspects of behaviors of the vision system is affected by which parameters. As the result, our model possesses the following two characteristics: First, it enable the derivation of an integral equation model with a Mexican-hat shape kernel as a necessary result of mechanisms (reduction of the retinal image resolution and a self-control mechanism formed by non-local interaction), in contrast to previous models that assumed various types of Mexican-hat shapes a priori. Second, it can explain two mutually contradicting phenomena called lightness contrast and assimilation. Moreover, our model explains the reason why lightness optical illusions do or do not occur via the magnitude of a control parameter. [ABSTRACT FROM AUTHOR]

Probabilistic finite state automata (PFSA) have found their applications in diverse systems. This paper presents the construction of an inner-product space structure on a class of PFSA over the real field via an algebraic approach. The vector space is constructed in a stationary setting, which eliminates the need for an initial state in the specification of PFSA. This algebraic model formulation avoids any reference to the related notion of probability measures induced by a PFSA. A formal language-theoretic and symbolic modeling approach is adopted. Specifically, semantic models are constructed in the symbolic domain in an algebraic setting. Applicability of the theoretical formulation has been demonstrated on experimental data for robot motion recognition in a laboratory environment. [ABSTRACT FROM AUTHOR]

An important research area in life sciences is devoted to modeling, prediction, and dynamics of gene-expression patterns. As clearly understood in these days, this enterprise cannot become satisfactory without acknowledging the role of the environment. To a representation of past, present, and most likely future states, we also encounter measurement errors and uncertainties. This paper surveys and improves recent advances in understanding the foundations and interdisciplinary implications of the newly introduced gene–environment networks, and it integrates the important theme of carbon dioxide emission reduction into the networks and dynamics. We also introduce some operational and managerial issues of practical working and decision making, expressed in terms of sliding windows, quadrants ( modules) of parametric effects, and navigating ( controlling) between such effects and directing them. Given data from DNA microarray experiments and environmental records, we extract nonlinear ordinary differential equations that contain parameters that have to be determined. For this, we employ modern (Chebychevian) approximation and (generalized semi-infinite) optimization. After this is provided, time- discretized dynamical systems are studied. A combinatorial algorithm with polyhedra sequences allows to detect the region of parametric stability. Finally, we analyze the topological landscape of gene–environment networks with its structural (in)stability. By embedding as a module and investigating CO2 emission control and figuring out game theoretical aspects, we conclude. This pioneering work is theoretically elaborated, practically devoted to health care, medicine, education, living conditions, and environmental protection, and it invites the readers to future research. [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel eigenface-based face recognition approach. First we describe a continuous model for facial feature extraction, involving the covariance operator associated with gradient of the 2-D image function. Then we provide a discretized version of this model. Face identification and verification procedures, using a supervised classification technique, are also proposed. [ABSTRACT FROM AUTHOR]

This paper describes a new algorithm for policy evaluation for Markov decision processes (MDP) that possess a quasi birth-death structure. The proposed algorithm is based on matrix analytic methods which use probabilistic concepts associated with restricting the underlying Markov process to certain state subsets. A telecommunications application example shows that the method offers significant computational reduction compared to a standard MDP policy evaluation approach. [ABSTRACT FROM AUTHOR]

Recent years have seen the introduction of non-local interactions in various fields. A typical example of a non-local interaction is where the convolution kernel incorporates short-range activation and long-range inhibition. This paper presents the relationship between non-local interactions and reaction-diffusion systems in the following sense: (a) the relationship between the instability induced by non-local interaction and diffusion-driven instability; (b) the realization of non-local interactions by reaction-diffusion systems. More precisely, it is shown that the non-local interaction of a Mexican-hat kernel destabilizes the stable homogeneous state and that this instability is related to diffusion-driven instability. Furthermore, a reaction-diffusion system that approximates the non-local interaction system with any even convolution kernel is shown to exist. [ABSTRACT FROM AUTHOR]

Interconnected systems are an important class of mathematical models, as they allow for the construction of complex, hierarchical, multiphysics, and multiscale models by the interconnection of simpler subsystems. Lagrange-Dirac mechanical systems provide a broad category of mathematical models that are closed under interconnection, and in this paper, we develop a framework for the interconnection of discrete Lagrange-Dirac mechanical systems, with a view toward constructing geometric structure-preserving discretizations of interconnected systems. This work builds on previous work on the interconnection of continuous Lagrange-Dirac systems (Jacobs and Yoshimura in J Geom Mech 6(1):67-98, 2014) and discrete Dirac variational integrators (Leok and Ohsawa in Found Comput Math 11(5), 529-562, 2011). We test our results by simulating some of the continuous examples given in Jacobs and Yoshimura (2014). [ABSTRACT FROM AUTHOR]

Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. It occurs most frequently as a disease of herbivores (e.g., cattle, goats and sheep) that acquire spores from direct contact with contaminated soil. In this paper, we formulate a new mathematical modeling framework to explore the spread of anthrax in the community. Our models include essential components such as fast and slow progression, carcass disposal and vector population. The existence of the disease-free equilibrium is discussed, the basic reproduction number is calculated, and the effect of carcass disposal on the basic reproduction number is studied. Our results suggest that carcass disposal may significantly reduce the spread of anthrax. Carcass disposal targeted at 85 % or more can be effective at stopping the spread of anthrax in the community. [ABSTRACT FROM AUTHOR]

In living organisms, cascades of covalent modification cycles are one of the major intracellular signaling mechanisms, allowing to transduce physical or chemical stimuli of the external world into variations of activated biochemical species within the cell. In this paper, we develop a novel method to study the stimulus-response of signaling cascades and overall the concept of pathway activation profile which is, for a given stimulus, the sequence of activated proteins at each tier of the cascade. Our approach is based on a correspondence that we establish between the stationary states of a cascade and pieces of orbits of a 2D discrete dynamical system. The study of its possible phase portraits in function of the biochemical parameters, and in particular of the contraction/expansion properties around the fixed points of this discrete map, as well as their bifurcations, yields a classification of the cascade tiers into three main types, whose biological impact within a signaling network is examined. In particular, our approach enables to discuss quantitatively the notion of cascade amplification/attenuation from this new perspective. The method allows also to study the interplay between forward and 'retroactive' signaling, i.e., the upstream influence of an inhibiting drug bound to the last tier of the cascade. [ABSTRACT FROM AUTHOR]

Depending on a field study for one of the largest iron and paints warehouses in Egypt, this paper presents a new multi-item periodic review inventory model considering the refunding quantity cost. Through this field study, we found that the inventory level is monitored periodically at equal time intervals. Returning a part of the goods that were previously ordered is permitted. Also, a shortage is permissible to occur despite having orders, and it is a combination of the backorder and lost sales. This model has been applied in both crisp and fuzzy environments since the fuzzy case is more suitable for real-life than crisp. The Lagrange multiplier technique is used for solving the restricted mathematical model. Here, the demand is a random variable that follows the normal distribution with zero lead-time. Finally, the model is followed by a real application to clarify the model and prove its efficiency. [ABSTRACT FROM AUTHOR]

In this paper we present a generalization of the classical bitangential Nevanlinna-Pick theory in which one bounds not the norm of the interpolating functions but their structured singular value This work was motivated by some problems arising in robust control of systems with structured uncertainty. This approach is based on the commutant lifting theory of Sz.-Nagy and Foias (1968) and extends previous work of Bercovici, Foias and Tannenbaum (1990) on structured matrix Nevanlinna-Pick interpolation. [ABSTRACT FROM AUTHOR]

The paper deals with terrestrial locomotion systems. Worms and snakes are living paragons for the development of biological inspired crawling robots. We set up certain models of worm- and snake-like locomotion systems and present purely analytical investigations in this paper. We try to follow an analytical framework, i.e., analyzing kinematics at first. Later on, we switch to dynamics and control of these models, to get hints for a technical development. The systems are modeled as chains of mass points. The mass points are interconnected via massless links with time-varying link-length. In contrast to the literature, the snake systems exhibit passive joints, but active links and rotatable skids. The combination of shape variation (via active links) together with the ground contact (via ideal spikes guaranteeing a one-sided velocity restriction) results in a global movement of the systems — undulatory locomotion. In dynamics, these link functions should be adjusted via, e.g., a force actuator between each mass point. Because it is impossible to determine a-priori these force outputs generating a desired gait, we apply an adaptive controller which adjusts these force outputs on-line on its own and λ -tracks a certain gait to achieve a movement of the whole system. [ABSTRACT FROM AUTHOR]

In this paper, we consider global stability for an anthrax model with distributed delay. The model incorporates vaccination and carcass disposal. The basic reproduction number of the anthrax model is derived, which completely determine the stability of equilibria. By using the direct Lyapunov method and constructing appropriate Lyapunov functional, the global stability for the anthrax epidemic model with distributed delay is investigated. It is shown that the disease-free equilibrium is globally asymptotically stable if the basic reproduction number is less than one, and the unique endemic equilibrium is globally asymptotically stable if the basic reproduction number is greater than one. In addition, numerical simulation results are presented to demonstrate the analytical findings. [ABSTRACT FROM AUTHOR]

In this paper, we present a fractional model of interacting phytoplankton species in which one species produces chemical which is stimulatory in nature to the other species. We study existence, uniqueness, permanence, persistence and stability of the solution. We introduce a new method to prove permanence and persistence, which may be applicable to several ecological models of fractional order. At the end we propose a discritization method and perform some numerical simulations to validate our analytical findings. [ABSTRACT FROM AUTHOR]

The building industry is becoming very important in sustainable development. The recently developed policies in European Union directives on energy and their transposition to Spanish regulations make the Energy Performance Certification process for buildings mandatory. Two software tools have been developed in Spain to carry out this process: Lider and Calener. These software tools have been used in this paper to simulate energy performance in new semidetached houses after taking into account the thermal envelope of the building and facilities. This has been done in different climatic zones in Spain and for all the possible energy ratings. Based on the energy rating and construction cost variables, it has been possible to obtain mathematical models that explain the behaviour of global costs of buildings based on energy ratings and climatic zones. Depreciation costs, maintenance costs, energy consumption and CO2emissions during the service life of a house have also been modelled. [ABSTRACT FROM AUTHOR]

This paper studies some problems related to the stability and the spectral radius of a finite set of matrices. A seasonal epidemic model is given to illustrate the use of the obtained results. In this example, the relationship between the obtained results and the stability of a discrete time periodic linear system is obtained. [ABSTRACT FROM PUBLISHER]

This paper proposes an identification method for estimating the parameters of a stable second-order system based on the impulse response experiment. From the impulse response experiment, the measured data are collected for implementing parameter estimation. By defining and minimizing a cost function, a Newton iterative algorithm is derived for estimating the parameters of the system. The multi-point identification method is used to show the effectiveness of the proposed Newton iterative algorithm. The results show that the estimated model by the proposed Newton iterative estimation method has higher accuracy. Based on the estimated model, a design method of the proportional derivative controller is presented according to the system dynamical performance. The simulation test shows that the proposed controller design method can meet the desired dynamic specifications. [ABSTRACT FROM AUTHOR]

Bregman iterative algorithms have been extensively used forand total variation regularization problems, allowing to obtain simple, fast and effective algorithms. In this paper, three already-available algorithms for geosounding inversion are modified by including them in a Bregman iterative procedure. The resulting algorithms are easy to implement and do not require any optimization package. Modelling results are presented for synthetic and field data, observing better convergence properties than the original versions, avoiding the need of any continuation descent procedure. [ABSTRACT FROM AUTHOR]

Human habitat connectivity, movement rates, and spatial heterogeneity have tremendous impact on malaria transmission. In this paper, a deterministic system of differential equations for malaria transmission incorporating human movements and the development of drug resistance malaria in an $$n$$ patch system is presented. The disease-free equilibrium of the model is globally asymptotically stable when the associated reproduction number is less than unity. For a two patch case, the boundary equilibria (drug sensitive-only and drug resistance-only boundary equilibria) when there is no movement between the patches are shown to be locally asymptotically stable when they exist; the co-existence equilibrium is locally asymptotically stable whenever the reproduction number for the drug sensitive malaria is greater than the reproduction number for the resistance malaria. Furthermore, numerical simulations of the connected two patch model (when there is movement between the patches) suggest that co-existence or competitive exclusion of the two strains can occur when the respective reproduction numbers of the two strains exceed unity. With slow movement (or low migration) between the patches, the drug sensitive strain dominates the drug resistance strain. However, with fast movement (or high migration) between the patches, the drug resistance strain dominates the drug sensitive strain. [ABSTRACT FROM AUTHOR]

The kinetic theory of active particles is used to model the formation and evolution of opinions in a structured population. The spatial structure is modeled by a network whose nodes mimic the geographic distribution of individuals, while the functional subsystems present in each node group together elements sharing a common orientation. In this paper we introduce a model, based on nonlinear and nonlinearly additive interactions among individuals, subsystems and nodes, related to the spontaneous evolution of opinion concerning given specific issues. Numerical solutions in a model situation not related with real data show how the mutual interactions are able to drive the subsystems opinion toward the emergence of collective structures characterizing this kind of complex systems. [ABSTRACT FROM AUTHOR]

Vendor–retailer collaboration has an important role in supply chain management. Although vendor–retailer collaboration results in better supply chain profit, collaboration is difficult to realize. This is because most vendors and retailers try to optimize their own profit. This paper applies the Stackelberg game with stochastic demand for the vendor–retailer system. The vendor as a leader determines the product price, and the retailer decides order quantity and frequency of price markdown. This study develops example and sensitivity analyses to illustrate the theory. Results show that the price markdown option has a better total supply chain profit than without a price markdown policy, and the vendor receives more benefit. For different demand variances, the retailer profit is more sensitive than the vendor profit. [ABSTRACT FROM AUTHOR]

Student academic underachievement is a concern of paramount importance in Europe, where around 15% of the students in the last high school courses do not achieve the minimum knowledge academic requirement. In this paper, we propose a model based on a system of differential equations to study the dynamics of the students’ academic performance in the German region of the North Rhine-Westphalia. This approach is supported by the idea that both good and bad study habits, are a mixture of personal decisions and influence of classmates. This model allows us to forecast the student academic performance by means of confidence intervals over the next few years. [ABSTRACT FROM PUBLISHER]

The consistency of identification algorithms for systems with colored noises is a main topic in system identification. This paper focuses on the extended stochastic gradient (ESG) identification algorithm for the multivariable linear systems with moving average noises. By integrating the noise regression terms and the noise model parameters into the information matrix and the parameter vector, and based on the gradient search principle, the ESG algorithm is presented. The unknown noise terms in the information matrix are replaced with their estimates. The convergence analysis shows that the parameter estimation error converges to zero under a persistent excitation condition. Two simulation examples are given to illustrate the effectiveness of the algorithm. [ABSTRACT FROM AUTHOR]

Effective tuberculosis (TB) control depends on case findings to discover infectious cases, investigation of contacts of those with TB, as well as appropriate treatment. Adherence and successful completion of the treatment are equally important. Unfortunately, due to a number of personal, psychosocial, economic, medical, and health service factors, a significant number of TB patients become irregular and default from treatment. In this paper, a mathematical model is developed to assess the impact of early therapy for latent TB and non-adherence on controlling TB transmission dynamics. Equilibrium states of the model are determined and their local stability is examined. With the aid of the center manifold theory, it is established that the model undergoes a backward bifurcation. Qualitative mathematical analysis of the model suggests that a high level of latent tuberculosis case findings, coupled with a decrease of defaulting rate, may be effective in controlling TB transmission dynamics in the community. Population-level effects of organized campaigns to improve early therapy and to guarantee successful completion of each treatment are evaluated through numerical simulations and presented in support of the analytical results. [ABSTRACT FROM AUTHOR]

This paper focuses on identification problems for Hammerstein systems with non-uniform sampling. By using the over-parameterization technique, we derive a linear regressive identification model with different input updating rates. To solve the identification problem of Hammerstein output error systems with the unmeasurable variables in the information vector, the least-squares-based iterative algorithm is presented by replacing the unmeasurable variables with their corresponding iterative estimates. The performances of the proposed algorithm are analysed and compared by using a numerical example. [ABSTRACT FROM PUBLISHER]

The mass of leaf is a key factor to estimate the magnitude of biogenic hydrocarbon emission. In this paper, following the minimum material consumption assumption and the conservation law of energy, we build a mathematical model to calculate the mass of leaf, crown and the whole tree, respectively. Also, we translate the shape of crown to match the solution of a second order differential equations with boundary value conditions. Meanwhile, we try to explore what does the climatic zone affect the shape and thickness of leaf. In the simulation section, by using the measured data for 14 trees in 3 different species, we present various simulation results through our models and formulas. Finally, following our models and formulas, we find out some hidden relationships: 1. There is an intrinsic link between the single leaf area and the hardness of the stem; 2. There is an interconnected relationship between the shape of leaf and the shape of tree; 3. There are lots of trees with large and thick leaves living in the torrid zone and few in the cold zone. [ABSTRACT FROM PUBLISHER]

In this paper, we introduce ordinary and delay differential equations to describe the interactions between a malignant tumour and the immune systemin vivoin the presence of human immunodeficiency virus (HIV) infection of CD4+T-cells. In the delay model, we take into account the time lags required by the healthy effector cell components to recognize the pathogens and tumour cells. The models consist of four populations: tumour cells, healthy effector cells (CD4+T-cells), effector cells infected by HIVs and free viral particles. The presence of delay term in the model leads to a notable increase in the complexity of the observed behaviour. We investigate the qualitative behaviour of the models and find the conditions that guarantee the asymptotic stability of the steady states. Numerical simulations are provided to illustrate and extend the theoretical results. The obtained results are consistent with the real phenomena and give a better understanding of cancer immunity and viral oncogenesis. [ABSTRACT FROM PUBLISHER]

Although diseases such as influenza, tuberculosis and SARS are transmitted through an environmentally mediated mechanism, most modeling work on these topics is based on the concepts of infectious contact and direct transmission. In this paper we use a paradigm model to show that environmental transmission appears like direct transmission in the case where the pathogen persists little time in the environment. Furthermore, we formulate conditions for the validity of this modeling approximation and we illustrate them numerically for the cases of cholera and influenza. According to our results based on recently published parameter estimates, the direct transmission approximation fails for both cholera and influenza. While environmental transmission is typically chosen over direct transmission in modeling cholera, this is not the case for influenza. [ABSTRACT FROM AUTHOR]

The aim of this paper is to analyze the recruitment effects of susceptible and infected individuals in order to assess the productivity of an organizational labor force in the presence of HIV/AIDS with preventive and HAART treatment measures in enhancing the workforce output. We consider constant controls as well as time-dependent controls. In the constant control case, we calculate the basic reproduction number and investigate the existence and stability of equilibria. The model is found to exhibit backward and Hopf bifurcations, implying that for the disease to be eradicated, the basic reproductive number must be below a critical value of less than one. We also investigate, by calculating sensitivity indices, the sensitivity of the basic reproductive number to the model's parameters. In the time-dependent control case, we use Pontryagin's maximum principle to derive necessary conditions for the optimal control of the disease. Finally, numerical simulations are performed to illustrate the analytical results. The cost-effectiveness analysis results show that optimal efforts on recruitment (HIV screening of applicants, etc.) is not the most cost-effective strategy to enhance productivity in the organizational labor force. Hence, to enhance employees' productivity, effective education programs and strict adherence to preventive measures should be promoted. [ABSTRACT FROM AUTHOR]

In this paper, a deterministic malaria transmission model in the presence of a drug-resistant strain is investigated. The model is studied using stability theory of differential equations, optimal control, and computer simulation. The threshold condition for disease-free equilibrium is found to be locally asymptotically stable and can only be achieved in the absence of a drug-resistant strain in the population. The existence of multiple endemic equilibria is also established. Both the Sensitivity Index (SI) of the model parameters and the Incremental Cost-Effectiveness Ratio (ICER) for all possible combinations of the disease-control measures are determined. Our results revealed among others that the most cost-effective strategy for drug-resistant malaria control is the combination of the provision of basic amenities (such as access to clean water, electricity, good roads, health care, and education) and treatment of infective individuals. Therefore, more efforts from policy-makers on the provisions of basic amenities and treatment of infectives would go a long way to combat the malaria epidemic. [ABSTRACT FROM AUTHOR]

Many financial optimization problems involve future values of security prices, interest rates and exchange rates which are not known in advance, but can only be forecast or estimated. Several methodologies have therefore, been proposed to handle the uncertainty in financial optimization problems. One such methodology is Robust Statistics, which addresses the problem of making estimates of the uncertain parameters that are insensitive to small variations. A different way to achieve robustness is provided by Robust Optimization which, given optimization problems with uncertain parameters, looks for solutions that will achieve good objective function values for the realization of these parameters in given uncertainty sets. Robust Optimization thus offers a vehicle to incorporate an estimation of uncertain parameters into the decision making process. This is true, for example, in portfolio asset allocation. Starting with the robust counterparts of the classical mean-variance and minimum-variance portfolio optimization problems, in this paper we review several mathematical models, and related algorithmic approaches, that have recently been proposed to address uncertainty in portfolio asset allocation, focusing on Robust Optimization methodology. We also give an overview of some of the computational results that have been obtained with the described approaches. In addition we analyse the relationship between the concepts of robustness and convex risk measures. [ABSTRACT FROM AUTHOR]

The efficient and reliable control of an electric arc furnace (EAF) is a challenging problem, due to the strong intercorrelation among process variables, the large dimension of the input and output space, the strong interaction among process variables, a large time delay, and a highly nonlinear behaviour. This paper presents a model that allows us to optimize the control and, therefore, the electric power consumption in an EAF. The data used for this study were collected from Bizkaia Steel Mill (Arcelor Company). Neural network and fuzzy logic techniques have been applied on these data in order to get an improved model of the casting temperature inside the furnace's hearth. First, we developed some neural network models with different topologies and input variables. Then we used the best model obtained in the previous step to combine it with a fuzzy logic technique to get the final model. Comparison with experimental data and other models is carried out to validate the proposed model. Finally, the conclusions and future studies are exposed. [ABSTRACT FROM AUTHOR]

Systems Biology is the science that aims to understand how biological function absent from macromolecules in isolation, arises when they are components of their system. Dedicated to the memory of Reinhart Heinrich, this paper discusses the origin and evolution of the new part of systems biology that relates to metabolic and signal-transduction pathways and extends mathematical biology so as to address postgenomic experimental reality. Various approaches to modeling the dynamics generated by metabolic and signal-transduction pathways are compared. The silicon cell approach aims to describe the intracellular network of interest precisely, by numerically integrating the precise rate equations that characterize the ways macromolecules’ interact with each other. The non-equilibrium thermodynamic or ‘lin–log’ approach approximates the enzyme rate equations in terms of linear functions of the logarithms of the concentrations. Biochemical Systems Analysis approximates in terms of power laws. Importantly all these approaches link system behavior to molecular interaction properties. The latter two do this less precisely but enable analytical solutions. By limiting the questions asked, to optimal flux patterns, or to control of fluxes and concentrations around the (patho)physiological state, Flux Balance Analysis and Metabolic/Hierarchical Control Analysis again enable analytical solutions. Both the silicon cell approach and Metabolic/Hierarchical Control Analysis are able to highlight where and how system function derives from molecular interactions. The latter approach has also discovered a set of fundamental principles underlying the control of biological systems. The new law that relates concentration control to control by time is illustrated for an important signal transduction pathway, i.e. nuclear hormone receptor signaling such as relevant to bone formation. It is envisaged that there is much more Mathematical Biology to be discovered in the area between molecules and Life. [ABSTRACT FROM AUTHOR]

For several decades, androgen suppression has been the principal modality for treatment of advanced prostate cancer. Although the androgen deprivation is initially effective, most patients experience a relapse within several years due to the proliferation of so-called androgen-independent tumor cells. Bruchovsky et al. suggested in animal models that intermittent androgen suppression (IAS) can prolong the time to relapse when compared with continuous androgen suppression (CAS). Therefore, IAS has been expected to enhance clinical efficacy in conjunction with reduction in adverse effects and improvement in quality of life of patients during off-treatment periods. This paper presents a mathematical model that describes the growth of a prostate tumor under IAS therapy based on monitoring of the serum prostate-specific antigen (PSA). By treating the cancer tumor as a mixed assembly of androgen-dependent and androgen-independent cells, we investigate the difference between CAS and IAS with respect to factors affecting an androgen-independent relapse. Numerical and bifurcation analyses show how the tumor growth and the relapse time are influenced by the net growth rate of the androgen-independent cells, a protocol of the IAS therapy, and the mutation rate from androgen-dependent cells to androgen-independent ones. [ABSTRACT FROM AUTHOR]