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High speed electrophoresis simulation for optimization of continuous flow electrophoresis and high performance capillary techniques: Part I. Computer model.

A computer program for high-speed simulation and optimization of electrophoretic processes has been developed for carrier-free systems of all kinds. The calculations are based on the one-dimensional dynamic (transient-state) model. The three-dimensional geometry of the simulation space can be chosen deliberately. With a highly efficient transport algorithm instead of complicated integration schemes for the transport equations, the calculation time can be effectively spent on various important parameters such as ionic strength, temperature, Joule heat, activity coefficients and concentration changes due to membranes. The parameter set of any carrier free electrophoretic method (i.e., continuous-flow electrophoresis, capillary isotachophoresis and high performance capillary zone electrophoresis) can be imported directly into the computer program by means of a graphic user interface. The program performs overnight-simulation of any electrophoretic system containing up to 15 components.

Computer Simulation↗

A practical model for mobile, residual, and entrapped NAPL in water-wet porous media.

Flow of nonvolatile nonaqueous phase liquid (NAPL) and aqueous phases that account for mobile, entrapped, and residual NAPL in variably saturated water-wet porous media is modeled and compared against results from detailed laboratory experiments. Residual saturation formation in the vadose zone is a process that is often ignored in multifluid flow simulators, which might cause an overestimation of the volume of NAPL that reaches the ground water. Mobile NAPL is defined as being continuous in the pore space and flows under a pressure gradient or gravitational body force. Entrapped NAPL is defined as being occluded by the aqueous phase, occurring as immobile ganglia surrounded by aqueous phase in the pore space and formed when NAPL is replaced by the aqueous phase. Residual NAPL is defined as immobile, nonwater entrapped NAPL that does not drain from the pore spaces and is conceptualized as being either continuous or discontinuous. Free NAPL comprises mobile and residual NAPL. The numerical model is formulated on mass conservation equations for oil and water, transported via NAPL and aqueous phases through variably saturated porous media. To account for phase transitions, a primary variable switching scheme is implemented for the oil-mass conservation equation over three phase conditions: (1) aqueous or aqueous-gas with dissolved oil, (2) aqueous or aqueous-gas with entrapped NAPL, and (3) aqueous or aqueous gas with free NAPL. Two laboratory-scale column experiments are modeled to verify the numerical model. Comparisons between the numerical simulations and experiments demonstrate the necessity to include the residual NAPL formation process in multifluid flow simulators.

Models, Theoretical↗

Genetics of recent habitat contraction and reduction in population size: does isolation by distance matter?

Fragmentation and loss of natural habitats are recognized as major threats to contemporary flora and fauna. Detecting past or current reductions in population size is therefore a major aim in conservation genetics. Statistical methods developed to this purpose have tended to ignore the effects of spatial population structure. However in many species, individual dispersal is restricted in space and fine-scale spatial structure such as isolation by distance (IBD) is commonly observed in continuous populations. Using a simulation-based approach, we investigated how comparative and single-point methods, traditionally used in a Wright-Fisher (WF) population context for detecting population size reduction, behave for IBD populations. We found that a complex 'quartet' of factors was acting that includes restricted dispersal, population size (i.e. habitat size), demographic history, and sampling scale. After habitat reduction, IBD populations were characterized by a stronger inertia in the loss of genetic diversity than WF populations. This inertia increases with the strength of IBD, and decreases when the sampling scale increases. Depending on the method used to detect a population size reduction, a local sampling can be more informative than a sample scaled to habitat size or vice versa. However, IBD structure led in numerous cases to incorrect inferences on population demographic history. The reanalysis of a real microsatellite data set of skink populations from fragmented and intact rainforest habitats confirmed most of our simulation results.

Alleles↗

Strategies for continual application of marker-assisted selection in an open nucleus population.

The objectives of this study were to develop and simulate the implementation of several strategies for repeated application of quantitative trait loci (QTL) detection and marker-assisted selection (MAS) and to compare the short-term and continual genetic responses. A finite locus model was simulated with 20 QTL randomly distributed across 30 chromosome. Three hundred markers were evenly spaced across the genome. Allelic effects were sampled from a double exponential distribution. A daughter design was used every generation to determine the marker alleles favorably associated to QTL alleles. The MAS was applied within family to young bulls, before progeny testing, as part of an open nucleus. Young bulls were selected using strategies based on 1) the single marker with greatest contrast (BEST1), 2) the sum of n greatest contrasts (BESTn), 3) the best n contrasts, limited to one per chromosome (LIMn), 4) the sum of all contrasts exceeding a given threshold n (THRESn), and 5) the sum of contrasts exceeding a threshold, but limited to one per chromosome (LIMT). The maximum progress was achieved by strategies that selected upon several markers flanking multiple QTL in each generation. When THRES was applied, the mean true breeding value (TBV) of selected bulls was increased by 11.98% (over conventional selection) versus 6.73% for BEST1 in the first generation. Applying a full genome scan in each generation allowed selection for different QTL across time. By selecting for multiple QTL over time, MAS maintained superiority over conventional selection for many generations.

Alleles↗

Pore-scale network model for three-phase flow in mixed-wet porous media.

We describe the development and application of a three-dimensional pore-scale network simulator for modeling capillary-dominated three-phase flow in porous media where the wettability varies from pore to pore, i.e., where each pore is allowed to have a different oil-water contact angle from a chosen distribution. Physical constraint equations for the remaining gas-oil and gas-water contact angles are implemented. In weakly wetted pores wetting films are absent, which reduces the continuity of the various phases in the network and increases the number of phase clusters that are disconnected from inlet or outlet. Mobilization of disconnected clusters requires incorporation of double and multiple displacement chains that involve a string of neighboring phase clusters, e.g., gas-->oil-->gas-->oil-->water. Furthermore, when multiple displacement chains cause disconnected clusters to reconnect to the outlet, the phase pressures at the outlet boundary are updated consistent with the pressures within the system. A number of benchmark simulations for systems with nonuniform wettability, mixed-wet with the larger pores oil-wet, are presented. The outcome of these simulations is presented as phase paths in saturation space and in the form of pore occupancy histograms and histograms of the length and type of displacement chains. Comparison of simulated saturation paths with those of an analytical capillary bundle model with the same wettability show good agreement where phase continuity is high and decreasing agreement as phase continuity in the network decreases. The saturation paths and occupancy and displacement statistics for a number of water-alternating-gas injection (WAG) simulations bring out the various features of the model, in particular, those related to the wettability. We find that multiple displacements do occur, mainly during higher-order WAG floods, although their effect on oil recovery seems limited. Variation of the outlet boundary pressure differences has an effect in certain regions of the saturation space that are defined by the analytical model.

Journal Article↗

Double layers and ion phase-space holes in the auroral upward-current region.

The dynamic evolution of the boundary between the ionosphere and auroral cavity is studied using 1D and 2D kinetic Vlasov simulations. The initial distributions of three singly ionized species (H+, O+, e-) are determined from space-based observations on both sides of an inferred strong double layer. The kinetic simulations reproduce features of parallel electric fields, electron distributions, ion distributions, and wave turbulence seen in satellite observations in the auroral upward-current region and, for the first time, demonstrate that auroral acceleration can be driven by a parallel electric field supported, in part, by a quasistable, strong double layer. In addition, the simulations verify that the streaming interaction between accelerated O+ and H+ populations continuously replenished by the double layer provides the free energy for the persistent formation of ion phase-space holes.

Journal Article↗

Cellular sodium transport in arterial wall--summary of studies by digital computer simulation.

The distribution of electrolytes between extracellular and intracellular compartments is of greater functional significance in biological tissues than the total amount. A method commonly employed for the study of a substance distribution among different spaces is the continuous outflow and radioisotope counting of a fragment of tissue previously incubated with a radioactive tracer (here 22Na+). The experimental data can be analyzed within the frame of a compartmental analysis system which is defined by transport rate constants (kij) and solved when all kij are numerically determined. In practical applications the direct solution requires measurements in different compartments or knowledge of the initial condition for each compartment, but this is not possible in most biological tissues where the experimentally observable data represent the summation of tracer in all compartments at each point in time. The availability of the SAAM (Simulation, Analysis And Modelling) computer program allows for a powerful simulation procedure to arrive at values for kij. Experimental data and specifications for a chosen model are entered in the SAAM format. A simulated 'inflow' experiment is made by the computer by assigning to kij some estimate values. All initial conditions are now zero, since at the beginning there is no radioactive tracer in any compartment. After a time equivalent in the experimental realm to achieving constant specific activity, a 'time change' programmed into the computer takes place so that the outflow part of the experiment is developed with the same kij as for the inflow part, the final conditions for the inflow before the time change being the initial conditions for the outflow. An iterative procedure modifies the initial estimates of kij to seek the best fit. By coupling a powerful simulation procedure to an advanced radionuclide tracer biological methodology, we have been able to find effects of the hormone aldosterone and of experimental hypertension on Na+ distribution in arterial wall years before such effects were demonstrated by purely conventional experimental techniques. This computer simulation procedure may be suited to other experimental situations in which outflow data are the only available.

Aldosterone↗

Spread of cancer cells in tissues: modelling and simulation.

Continuing previous studies in which tumor diseases were interpreted as unstable control loops, the present paper tries to determine the spatial structure and the time behaviour of cell renewal systems. For this purpose a computer model for the two-dimensional cell space was developed, which is described by a set of specifications and growth statements. Selected case studies are then simulated by means of a digital computer (CYBER 76). The development of this model enables a deeper insight into the structure and function of disturbed cell renewal processes. Furthermore, it is possible with this computer model to simulate simple basic cases which, in reality, could hardly or not at all be tested.

Animals↗

Space-time relationship in continuously moving table method for large FOV peripheral contrast-enhanced magnetic resonance angiography.

Data acquisition using a continuously moving table approach is a method capable of generating large field-of-view (FOV) 3D MR angiograms. However, in order to obtain venous contamination-free contrast-enhanced (CE) MR angiograms in the lower limbs, one of the major challenges is to acquire all necessary k-space data during the restricted arterial phase of the contrast agent. Preliminary investigation on the space-time relationship of continuously acquired peripheral angiography is performed in this work. Deterministic and stochastic undersampled hybrid-space (x, k(y), k(z)) acquisitions are simulated for large FOV peripheral runoff studies. Initial results show the possibility of acquiring isotropic large FOV images of the entire peripheral vascular system. An optimal trade-off between the spatial and temporal sampling properties was found that produced a high-spatial resolution peripheral CE-MR angiogram. The deterministic sampling pattern was capable of reconstructing the global structure of the peripheral arterial tree and showed slightly better global quantitative results than stochastic patterns. Optimal stochastic sampling patterns, on the other hand, enhanced small vessels and had more favourable local quantitative results. These simulations demonstrate the complex spatial-temporal relationship when sampling large FOV peripheral runoff studies. They also suggest that more investigation is required to maximize image quality as a function of hybrid-space coverage, acquisition repetition time and sampling pattern parameters.

Algorithms↗

Solution of the two-star model of a network.

The p-star model or exponential random graph is among the oldest and best known of network models. Here we give an analytic solution for the particular case of the two-star model, which is one of the most fundamental of exponential random graphs. We derive expressions for a number of quantities of interest in the model and show that the degenerate region of the parameter space observed in computer simulations is a spontaneously symmetry-broken phase separated from the normal phase of the model by a conventional continuous phase transition.

Journal Article↗

Continuous homogeneous asymmetric transfer hydrogenation of ketones: lessons from kinetics.

Is polymer enlargement of homogeneous catalysts a tedious task? Is not batch operation with homogeneous catalysts the optimum performance point for homogeneous catalysis? Is kinetic modelling relevant to more than academic questions in homogeneous catalysis? Can all answers for a given system be answered satisfactory? In the authors' view, answers to these questions are no, no, yes, and depends. Polymer enlargement allowed the continuous operation of transfer hydrogenation in a chemical membrane reactor with total turnover numbers of up to 2.6 x 10(3) and a space-time yield of 0.58 kg L(-1) d(-1) with an enantiomeric ratio of 26.8 (enantiomeric excess 92.8 %) for a conversion level of 80 %. This was predicted from simulation conducted with a model from kinetic batch experiments adopted for continuous application. These simulations for the polymer-enlarged and the unmodified catalyst show that achieving comparable performance cannot be obtained by batch operation.

Alcohols↗

Effect of hindlimb suspension simulation of microgravity on in vitro immunological responses.

The effects of microgravity on the immune system are largely unknown, but understanding such effects becomes increasingly important as space exploration continues and mission duration increases. Reductions in postflight human T cell reactivity to mitogens is well documented. Similar results have been obtained using a clinostat as an in vitro model of microgravity. In this study, a rat tail suspension model of weightlessness was used to examine in vitro lymphocyte proliferation in response to mitogens. Experiments were designed to uncover potential deficits in events related to proliferation including cell surface protein and IL-2 receptor (IL-2R) expression, interleukin-2 (IL-2) production, and accessory cells. Suspension of rats for 1 week led to a significant depression in [3H]thymidine incorporation by mitogen-stimulated peripheral blood lymphocytes (PBL) but only a small decrease in the proliferation of lymph node lymphocytes and splenocytes. There were no changes in the percentages of cells expressing CD4, CD5, CD8 or immunoglobulin. Moreover, no changes in IL-2 production or IL-2R expression were observed. More esterase-positive macrophages were detected in all lymphatic tissues of suspended rats, but there was no corresponding increase in the percentage of cells bearing the macrophage markers OX41 or OX42. This increase in the number of macrophages may be related to the observed suppression of lymphocyte proliferation. The tissue specificity of the decrease in mitogen activation indicates that there may be a compartmentalized response in the rats tested in the hindlimb suspension model.

Animals↗

Long-term memory contribution as applied to the motion of discrete dynamical systems.

We consider the evolution of logistic maps under long-term memory. The memory effects are characterized by one parameter, alpha. If it equals to zero, any memory is absent. This leads to the ordinary discrete dynamical systems. For alpha=1 the memory becomes full, and each subsequent state of the corresponding discrete system accumulates all past states with the same weight just as the ordinary integral of first order does in the continuous space. The case with 0 0.15 the memory effects win over chaos.

Algorithms↗

Robust self-localisation and navigation based on hippocampal place cells.

A computational model of the hippocampal function in spatial learning is presented. A spatial representation is incrementally acquired during exploration. Visual and self-motion information is fed into a network of rate-coded neurons. A consistent and stable place code emerges by unsupervised Hebbian learning between place- and head direction cells. Based on this representation, goal-oriented navigation is learnt by applying a reward-based learning mechanism between the hippocampus and nucleus accumbens. The model, validated on a real and simulated robot, successfully localises itself by recalibrating its path integrator using visual input. A navigation map is learnt after about 20 trials, comparable to rats in the water maze. In contrast to previous works, this system processes realistic visual input. No compass is needed for localisation and the reward-based learning mechanism extends discrete navigation models to continuous space. The model reproduces experimental findings and suggests several neurophysiological and behavioural predictions in the rat.

Animals↗

The vascular network of tumours--what is it not for?

It is becoming almost a dogma that tumours cannot grow beyond 1-2 mm(3) unless they are supported by a rich vascular supply 1. It is true that tumours promote angiogenesis and that highly vascularized carcinomas have, in general, a more aggressive clinical course than carcinomas of low vascularization 23. However, a study of intratumoral angiogenesis reveals that the newly formed vessels are commonly deprived of those structural qualities that would allow them to perform an optimal oxygenation function 3. Thus, most tumours, irrespective of their angiogenic status, behave as if they were 'hypoxic', urging (via angiogenic mediators) for, what would look paradoxical at first sight, more defective angiogenesis. It is hypothesized that tumour cells can grow into solid neoplasms by exploiting the host's pre-existing vessels, without the need for new blood vessel formation. Neovascularization, however, may be important for tumours with an exophytic pattern of growth as these, by their very nature, lose the host's sheltering stroma. Shifting to anaerobic glycolysis and activation of anti-apoptotic pathways are complementary mechanisms for tumour cell survival and growth. Besides, continuous and indiscriminate production of a defective vascular network ensures an increased metastatic potential since the newly formed intratumoral vessels, simulating venular-like spaces, are easily permeable to tumour cells, facilitating metastases.

Angiogenesis Inhibitors↗

View dependence in scene recognition after active learning.

Human spatial encoding of three-dimensional navigable space was studied, using a virtual environment simulation. This allowed subjects to become familiar with a realistic scene by making simulated rotational and translational movements during training. Subsequent tests determined whether subjects could generalize their recognition ability by identifying novel-perspective views and topographic floor plans of the scene. Results from picture recognition tests showed that familiar direction views were most easily recognized, although significant generalization to novel views was observed. Topographic floor plans were also easily identified. In further experiments, novel-view performance diminished when active training was replaced by passive viewing of static images of the scene. However, the ability to make self-initiated movements, as opposed to watching dynamic movie sequences, had no effect on performance. These results suggest that representation of navigable space is view dependent and highlight the importance of spatial-temporal continuity during learning.

Adult↗

From gravity and the organism to gravity and the cell.

This workshop on Gravity and the Cell was modeled on a 1968 conference on Gravity and the Organism. Each conference tried to identify the most salient scientific questions about how gravity is important to living systems. In the roughly two decades between the conferences there have been impressive advances in experimental methods, but the major scientific questions that have driven their applications to problems of gravitational biology, i.e., our broad research goals, remain much the same. In the case of plant research, improvements and extensions of biochemical techniques for investigating the ways organisms use environmental (g-force) information in salubrious ways has kept pace with progress in plant biochemistry. We now know much more about the roles of organic and inorganic substances that plants employ for information transfer and growth regulation and about the avenues and mechanisms for transport of those key substances within organisms. We have seen the acceptance of a "local control" concept that regulation of g-responses depends critically on plasmodesmata and gap junctions which allow plants and animals to throttle the transport of growth regulators across tissue boundaries often, especially in the case of plants, far removed from the morphological regions of concentration of statocytes that were once thought to be the exclusive bioaccelerometers used by plants. NASA's sponsorship of ground-based research in gravitational biology has served as important underpinning for orbital flight programs in space biology. The currently most noteworthy research area of ignorance is the mechanism by which the physical event of g-force susception becomes the biological process of g-force perception. Only rarely has it been possible to perform a definitive test of a theory of mechanism of gravity perception. Therefore, experimental research efforts in gravitational physiology still are essentially dependent on exploratory studies for which stimulus/response experiments require experimental manipulation of test subjects' g-force environment. Many research efforts have focused narrowly on contrasting the responses of test subjects to only two gravitational environments, 1 g versus real or simulated zero g. Much less effort has been devoted to studies at other g levels. For experiments in gravitational physiology three rotating machines have made, and no doubt will continue to make, important contributions: the centrifuge, the clinostat, and, most of all, the orbiting space vehicle. Some research trends, viewpoints, and shifts of emphasis are discussed.

Animals↗