Evaluation of the cardiovascular system using NMR

The current status and suggestions of the future potential for nuclear magnetic resonance imaging of the cardiovascular system are described. With many of the potential applications, there is overlap with existing methods. For example, imaging of the left ventricle can be accomplished with either echocardiography or radionuclide techniques with adequate evaluation of the left ventricular function. At current costs these conventional techniques may provide a more cost-effective approach for morphologic and functional assessment of the cardiovascular system. For this type of imaging, the advantages of NMR include its excellent resolution, the inherent tissue contrast, the sensitivity to blood motion, the 3-dimensional measure, and the lack of ionizing radiation. Because of these, NMR could provide an important adjunct for evaluation of the cardiovascular system. However for NMR to achieve its full promise as a cardiovascular imaging technique, some of its unique potentials need to be developed. These include: the ability to reliably image at least the proximal coronary arteries, the ability to delineate regional myocardial blood flow distribution, the ability to evaluate regional metabolic activity such as high-energy phosphate metabolites, and the ability to characterize myocardial disease using proton T1 and T2 alterations.     

The pea aphid, Acyrthosiphon pisum: an emerging genomic model system for ecological, developmental and evolutionary studies

Aphids display an abundance of adaptations that are not easily studied in existing model systems. Here we review the biology of a new genomic model system, the pea aphid, Acyrthosiphon pisum. We then discuss several phenomena that are particularly accessible to study in the pea aphid: the developmental genetic basis of polyphenisms, aphid-bacterial symbioses, the genetics of adaptation and mechanisms of virus transmission. The pea aphid can be maintained in the laboratory and natural populations can be studied in the field. These properties allow controlled experiments to be performed on problems of direct relevance to natural aphid populations. Combined with new genomic approaches, the pea aphid is poised to become an important model system for understanding the molecular and developmental basis of many ecologically and evolutionarily relevant problems.     

Numerical simulation of cardiovascular dynamics with different types of VAD assistance

A variety of methods by which mechanical circulatory support (MCS) can be provided have been described. However, the haemodynamic benefits of the different methods have not been adequately quantified. The aim of this paper is to compare the haemodynamic effects of six forms of MCS by numerical simulation. Three types of ventricular assist device (VAD) are studied: positive displacement; impeller and a novel reciprocating-valve design. Similarly, three pumping modes are modelled: constant flow; counterpulsation and copulsation. The cardiovascular system is modelled using an approach developed previously, using the concentrated parameter method by considering flow resistance, vessel elasticity and inertial effects of blood in individual conduit segments. The dynamic modelling of displacement and impeller pumps is represented by VAD inlet/outlet flow-rate changes. The dynamics of the reciprocating-valve pump is modelled with a specified displacement profile. Results show that in each simulation, the physiological variables of mean arterial pressure and systemic flow are adequately maintained. Modulation of the impeller pump flow profile produces a small (5 mmHg) oscillatory component to arterial pressure, whereas the displacement and reciprocating-valve pumps generate substantial arterial pressure and flow pulsatility. The impeller pump requires the least power input, the reciprocating valve pump slightly more, and the displacement pump the most. The in parallel configuration of the impeller and displacement pump designs with respect to the left ventricle provides near complete unloading and can cause the aortic valve to remain closed throughout the entire cardiac cycle with the attendant risk of aortic valve leaflet fusion following prolonged support. The in series configuration of the reciprocating-valve pump avoids this shortcoming but activation must be carefully synchronized to the cardiac cycle to allow adequate coronary perfusion. The reciprocating-valve pump is associated with haemodynamic advantages and a favourable power consumption.     

How plants changed the world: Using qualitative reasoning to explain plant macroevolution's effect on the long-term carbon cycle

We present a qualitative reasoning model of how plant colonization of land during the mid Paleozoic era (450–300 million years ago) altered the long-term carbon cycle resulting in a dramatic decrease in global atmospheric carbon dioxide levels. This model is aimed at facilitating learning and communication about how interactions between biological and geological processes drove system behavior. The model is developed in three submodels of the main system components, namely how competition for limited land habitat drove natural selection for increasing adaptations to life on land; how these adaptations resulted in increased formation of organic-rich sedimentary rocks (coal); and how these adaptations altered weathering of calcium and magnesium silicate rocks, resulting in increased deposition of inorganic carbonates in oceans. These separate submodels are then assembled to derive the full dynamic model of plant macroevolution, colonization of land, and plummeting carbon dioxide levels that occurred during the mid Paleozoic. The qualitative reasoning framework supports explicit representation of causal feedbacks — as with previously developed systems analysis models — but also supports simulation of system dynamics arising from the configuration of entities in the system. The ability of qualitative reasoning to provide causal accounts (explanations) of why certain phenomena occurred and when, is a powerful advantage over numerical simulation such as the complex GEOCARB models, where explanation must be left to interpretation by experts.     

A new integrated method for analyzing heart mechanics using a cell-hemodynamics-autonomic nerve control coupled model of the cardiovascular system

A model of the cardiovascular system coupling cell, hemodynamics, and autonomic nerve control function is proposed for analyzing heart mechanics. We developed a comprehensive cardiovascular model with multi-physics and multi-scale characteristics that simulates the physiological events from membrane excitation of a cardiac cell to contraction of the human heart and systemic blood circulation and ultimately to autonomic nerve control. A lumped parameter model is used to compute the systemic and pulmonary circulations interacting with the cardiac cell mechanism. For autonomic control of the cardiovascular system, we used the approach suggested by Heldt et al. [2002. Computational modeling of cardiovascular response to orthostatic stress. J. Appl. Physiol. 92, 1239–1254] (Heldt model), including baroreflex and cardiopulmonary reflexes. We assumed sympathetic and parasympathetic pathways for the nerve control system. The cardiac muscle response to these reflex control systems was implemented using the activation-level changes in the L-type calcium channel and sarcoplasmic/endoplasmic reticulum calcium ATPase function based on experimental observations. Using this model, we delineated the cellular mechanism of heart contractility mediated by nerve control function. To verify the integrated method, we simulated a 10% hemorrhage, which involves cardiac cell mechanics, circulatory hemodynamics, and nerve control function. The computed and experimental results were compared. Using this methodology, the state of cardiac contractility, influenced by diverse properties such as the afterload and nerve control systems, is easily assessed in an integrated manner.     

Declarative simulation of dynamicals systems: the 812 programming language and its application to the simulation of genetic networks

A major part of biological processes can be modeled as dynamical systems (DS), that is, as a time-varying state. In this article, we advocate a declarative approach for prototyping the simulation of DS. We introduce the concepts of collection, stream and fabric. A fabric is a multi-dimensional object that represents the successive values of a structured set of variables. A declarative programming language, called 8 1/2 has been developed to support the concept of fabrics. Several examples of working 8 1/2 programs are given to illustrate the relevance of the fabric data structure for simulation applications and to show how recursive fabric definitions can be easily used to model various biological phenomena in a natural way (a resolution of PDE, a simulation in artificial life, the Turing diffusion-reaction process and various examples of genetic networks). In the conclusion, we recapitulate several lessons we have learned from the 8 1/2 project.     

Experimental application of a multistep kinetic model for natural cytotoxicity: determination of rate constants for lytic programming and killer-cell-independent lysis

A multistep kinetic model for natural cytotoxicity reactions in vitro is described that includes consideration of the effect of nonlytic target-binding lymphocytes on the experimentally determined kinetic parameters. The expression for the maximal velocity, Vmax, obtained using this model is essentially identical to that obtained using simpler models, whereas the expression for the apparent Michaelis constant, KappM, is considerably more complex. As a first step in the application of this model, experiments were designed to determine the relative contribution of some of the component terms to the value of KappM. Methods were developed that allow for experimental determination of the rate constants for both lytic programming and killer-cell-independent lysis (KCIL) steps in the cytolytic process. The results obtained support lytic programming as the rate-determining step in natural cytotoxicity reactions and demonstrate that terms related to nonlytic target-binding lymphocytes contribute significantly to experimentally determined values for KappM. In addition, the methods developed for the determination of the rates of lytic programming and KCIL should prove useful for various studies of the mechanism of cytotoxicity and the effects of drugs and disease on such phenomena.     

CADCS simulation of the closed-loop cardiovascular system

A pulsatile simulator of the closed-loop cardiovascular system, designed to solve simulation, identification and control problems in a research and education context, is presented. Its implimentation makes use of a command-driven interactive program for simulation of non-linear ordinary differential equations. The flexibility of the simulator is demonstrated by the results presented which refer to a basal steady-state circulatory condition as well as a transient induced by an abrupt change in peripheral resistance.     

A fluid dynamics model of the growth of phototrophic biofilms

A system of nonlinear hyperbolic partial differential equations is derived using mixture theory to model the formation of biofilms. In contrast with most of the existing models, our equations have a finite speed of propagation, without using artificial free boundary conditions. Adapted numerical scheme will be described in detail and several simulations will be presented in one and more space dimensions in the particular case of cyanobacteria biofilms. Besides, the numerical scheme we present is able to deal in a natural and effective way with regions where one of the phases is vanishing.     

A multiscale approach for modelling wave propagation in an arterial segment

A mathematical model of blood flow through an arterial vessel is presented and the wave propagation in it is studied numerically. Based on the assumption of long wavelength and small amplitude of the pressure waves, a quasi-one-dimensional (1D) differential model is adopted. It describes the non-linear fluid-wall interaction and includes wall deformation in both radial and axial directions. The 1D model is coupled with a six compartment lumped parameter model, which accounts for the global circulatory features and provides boundary conditions. The differential equations are first linearized to investigate the nature of the propagation phenomena. The full non-linear equations are then approximated with a numerical finite difference method on a staggered grid. Some numerical simulations show the characteristics of the wave propagation. The dependence of the flow, of the wall deformation and of the wave velocity on the elasticity parameter has been highlighted. The importance of the axial deformation is evidenced by its variation in correspondence of the pressure peaks. The wave disturbances consequent to a local stiffening of the vessel and to a compliance jump due to prosthetic implantations are finally studied.     

Ionic selectivity, saturation and block in gramicidin A channels: I. Theory for the electrical properties of ion selective channels having two pairs of binding sites and multiple conductance states.

A model for the gramicidin A channel is proposed which extends existing models by adding a specific cationic binding site at each entrance to the channel. The binding of ions to these outer channel sites is assumed to shift the energy levels of the inner sites and barriers and thereby alter the channel conductance. The resulting properties are analyzed theoretically for the simplest case of two inner sites and a single energy barrier. This for-site model (two outer and two inner) predicts that the membrane potential at zero current (Uo) should be a Goldman-Hodgkin-Katz equation with concentration-dependent permeability ratios. The coefficients of the concentration-dependent terms are shown to be related to the peak energy shifts of the barrier and to the binding constants of the outer sites. The thory also predicts the channel conductance in symmetrical solutions to exhibit three limiting behaviors, from which the properties of the outer and inner sites can be characterized. In two-cation symmetrical mixtures the conductance as a function of mole fraction is shown to have a minimum, and the related phenomenon of inhibition and block exerted by one ion on the other is explained explicitly by the theory. These various phenomena, having ion interactions in a multiply occupied channel as a common physical basis, are all related (by the theory) through a set of measurable parameters describing the properties of the system.     

The visual system as a constraint on the survival and success of specific artworks

Why should vision science turn its gaze towards artworks? One possibility is that understanding visual processing might yield some fundamental insight into the nature of art. However, there are many examples of phenomena that can be seen - such as automobiles, clouds or leaves - but which are not explained in any deep sense by the properties of human visual perception. We examine one art historical question that might benefit from knowledge about the visual system: why do some artworks 'survive' historically while others fade into the dustbin of time? One possible reason, suggested by studies of rapid visual categorization, is that some objects are recognized more quickly and easily than others and thus are less culturally specific in terms of pictorial representation. A second, related, explanation is that many artistic techniques use the eyes as a channel to evoke other senses, cognition, emotions and the motor system. 'Art' is a social and historical construct - after all, the concept of 'fine art' was invented in the 18th century - and thus many aspects of artistic appreciation are specific to particular cultural and historical contexts. Some great works, however, may be adopted by successive generations because of an ability to appeal to a shared perceptual system.     

Application of the advanced system for implant stability testing (ASIST) to natural teeth for noninvasive evaluation of the tooth root interface

In this paper we present the development of the Advanced System for Implant Stability Testing (ASIST) for application to natural teeth. The ASIST uses an impact measurement combined with an analytical model of the system and surrounding support to provide a measure of the interface stiffness. In this study, an analytical model is developed for a single-rooted natural tooth allowing the ASIST to estimate the stiffness characteristics of the periodontal ligament (PDL). The geometry and inertia parameters of the tooth model are presented in two ways: (1) using full CT scans of the individual tooth and (2) using an approximate geometry model with estimates of only the tooth length and diameter. The developed system is evaluated with clinical data for patients undergoing orthodontic treatment. This study shows that ASIST technique can be applied to natural teeth to estimate the stiffness characteristics of the PDL. The developed system can provide a valuable clinical tool for assessment of tooth stability properties and PDL stiffness in a variety of clinical situations such as dental trauma, orthodontics, and periodontology.     

A prototype segmental model for blood flow and heat transfer in the limb.

A general modeling technique for characterizing the blood flow and heat tranfer properties in the human limb is reported in this paper. The basic idea is to take the segmental approach so that a lumped model for each segment can be constructed. Consequently, a prototype segmental computer model is proposed which describes, in general terms, the interrelationships between the circulatory system and the thermal system of the limb. Simulation study of digital response to hand cooling is made and the results agree very well with the experimental data.     

Automated refinement and inference of analytical models for metabolic networks

The reverse engineering of metabolic networks from experimental data is traditionally a labor-intensive task requiring a priori systems knowledge. Using a proven model as a test system, we demonstrate an automated method to simplify this process by modifying an existing or related model--suggesting nonlinear terms and structural modifications--or even constructing a new model that agrees with the system's time series observations. In certain cases, this method can identify the full dynamical model from scratch without prior knowledge or structural assumptions. The algorithm selects between multiple candidate models by designing experiments to make their predictions disagree. We performed computational experiments to analyze a nonlinear seven-dimensional model of yeast glycolytic oscillations. This approach corrected mistakes reliably in both approximated and overspecified models. The method performed well to high levels of noise for most states, could identify the correct model de novo, and make better predictions than ordinary parametric regression and neural network models. We identified an invariant quantity in the model, which accurately derived kinetics and the numerical sensitivity coefficients of the system. Finally, we compared the system to dynamic flux estimation and discussed the scaling and application of this methodology to automated experiment design and control in biological systems in real time.     

Theoretical approach to blood ejection from the human left ventricle

An ejection dynamics mathematical model of human left ventricle (LV) based on physiological data of human heart is proposed in this study. The mathematical equations were expressed in terms of vorticity-stream function equations in a prolate spheroidal coordinate system. These equations combined with specified boundary conditions were numerically solved by using an alternating-direction-implicit (ADI) algorithm with second order accuracy. The unsteady aspects of the ejection process were subsequently introduced into the numerical simulation. The numerical results have shown that the present ellipsoidal model could be available to simulate the ejection process of the human LV. Such a model combined with cardiac muscle mechanics could be studied further to determine altered left ventricular function in cardiac diseases.     

Dynamics of a host–parasitoid model with Allee effect for the host and parasitoid aggregation

In this paper, a discrete-time host–parasitoid model is investigated. Two biological phenomena, the Allee effect of the host population and the aggregation of the parasitism, are considered in our mathematical model. Through extensive numerical simulations, we gain some interesting findings related to Allee effect from this research. Firstly, the ranges of parameter, in which the population dynamics is chaos, are compressed when Allee effect is added. Secondly, the sensitivity to initial conditions of the host–parasitoid system decreased after adding Allee effect. Thirdly, without Allee effect, we observed two complicated dynamics, intermittent chaos and supertransients. However, when Allee effect is included, these two phenomena are replaced by another kind of phenomenon-period alternation, where chaos is eliminated. From above three novel findings, it can be concluded that dynamic complexities are alleviated by Allee effect. This conclusion is crucial in resolving the discrepancy between real population dynamics and theoretical predictions. Furthermore, the importance of this research is to help us understand the mechanisms inducing the irregular fluctuations of the natural populations.     

A computerized respiratory system including test functions of lung and circulation

The design of a microcomputer-controlled ventilator for automatic performance of lung function and circulatory tests has been described. It incorporates the characteristics of normal mechanical ventilation and also allows one to perform a multitude of test procedures for lung function and circulatory studies in paralyzed animals. The major components of the setup are a pump assembly with solenoid valves to direct gas flow, an electromechanical servo system, and a MS-DOS microcomputer system. The pump assembly has been constructed as a relatively simple device. Great versatility is created by the use of a microcomputer for the control of the ventilator. The software can be easily adapted to several other types of experimental studies. Besides the keyboard input the ventilator can be controlled by a remote computer system. This allows one to run an experimental protocol automatically and to use it in closed-loop servo ventilation. The flexibility in the choice of the respiratory parameters makes the ventilator suitable for lung function and circulatory studies during artificial ventilation. The ventilator has been successfully used in different animal studies during the last 6 yr.     

Circulatory system of rainbow trout Oncorhynchus mykiss (Walbaum): a corrosion cast study

The present study describes and visualizes the circulatory system of rainbow trout with emphasis on the heart and main blood vessels, employing corrosion cast methodology. Ten rainbow trout (Oncorhynchus mykiss (Walbaum) of 1000 g average weight were obtained from a commercial fish farm. Fish were anaesthetised using a benzocain solution in ethanol. After 40 min, the fish were killed using an overdose of the benzocain solution. The aorta caudalis and aorta coeliaco‐mesentric were cannulated and attempts were made to fill the blood vessels and heart with fluid artificial resin made on the basis of methylmetacrylate. The fish were further prepared by submersion for 12–24 h in a room temperature waterbath until polymerisation and hardening of the methylmetacrylate was complete. This was followed by 24–48 h submersion in a 25% solution of KOH to obtain full maceration of the organic tissues. Various parts of the heart and blood vessels were retained in their natural positions, thereby demonstrating the anatomical details of the main circulatory system. Main elements depicted included the sinus venosus, atrium, ventricle, bulbus arteriosus and related vessels such as the dorsal aorta, subclavian vein, hepatic vein, common cardinal vein, coeliaco‐mesenteric artery, gastero‐intestinal artery, and dorsal intestinal artery. Related smaller vessels were also determined.     

Role of blood-oxygen transport in thermal tolerance of the cuttlefish, Sepia officinalis

Mechanisms that affect thermal tolerance of ectothermic organismshave recently received much interest, mainly due to global warmingand climate-change debates in both the public and in the scientificcommunity. In physiological terms, thermal tolerance of severalmarine ectothermic taxa can be linked to oxygen availability,with capacity limitations in ventilatory and circulatory systemscontributing to oxygen limitation at extreme temperatures. Thepresent review briefly summarizes the processes that definethermal tolerance in a model cephalopod organism, the cuttlefishSepia officinalis, with a focus on the contribution of the cephalopodoxygen-carrying blood pigment, hemocyanin. When acutely exposedto either extremely high or low temperatures, cuttlefish displaya gradual transition to an anaerobic mode of energy productionin key muscle tissues once critical temperatures (T_crit) arereached. At high temperatures, stagnating metabolic rates anda developing hypoxemia can be correlated with a progressivefailure of the circulatory system, well before T_crit is reached.However, at low temperatures, declining metabolic rates cannotbe related to ventilatory or circulatory failure. Rather, wepropose a role for hemocyanin functional characteristics asa major limiting factor preventing proper tissue oxygenation.Using information on the oxygen binding characteristics of cephalopodhemocyanins, we argue that high oxygen affinities (= low P₅₀values), as found at low temperatures, allow efficient oxygenshuttling only at very low venous oxygen partial pressures.Low venous PO₂s limit rates of oxygen diffusion into cells,thus eventually causing the observed transition to anaerobicmetabolism. On the basis of existing blood physiological, molecular,and crystallographical data, the potential to resolve the roleof hemocyanin isoforms in thermal adaptation by an integratedmolecular physiological approach is discussed.