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Biology and physiology


Study of the Folding - Unfolding Transition in Globular Proteins truecm

Proteins, unlike simple polymers, fold to a unique spatial conformation through a process which is little understood. Here we want to measure directly a good parameter to describe the transition, and we choose the average size of the molecule. Schematically, the experimental setup consists in confining a monolayer of protein molecules between two flat plates which are free to move, and monitor the distance between the plates, the swelling of the molecules pushing them apart as one crosses the transition. We measure variations of the plates' separation interferometrically, with 1 Angstrom resolution. At present the apparatus is essentially ready and we are about to start the measurements. truecm

G. Zocchi, M.H. Jensen and K. Sneppen truecm

Nucleation of Microtubules truecm

Tubulin is an important protein in the cytoskeleton of all eukaryotes. It is a dimer 8 nm long and 4 nm in diameter. It has a remarkable tendency to aggregate (or polymerize) into long and very rigid hollow rods, called microtubules. We study the spontaneous nucleation of microtubules in vitro in the limit of very slow and very fast nucleation rates. The rate of nucleation is a function of temperature, T, and concentration of tubulin, C. At very low concentrations or temperatures (, C), the rate is unmeasurably slow. At moderate temperatures or concentrations (CC, ), individual nucleation events can be recorded by measuring the density of single microtubules directly. Since microtubules are effectively one-dimensional, they consume the supply of tubulin quite slowly and their nucleation can be monitored for relatively long times at modest rates by direct observation under an optical microscope. Upon quenching to very high temperatures or concentrations, nucleation proceeds rapidly and direct observation is difficult. In this second nucleation regime, indirect observations of the solution turbidity are used as a measure of the microtubule density. Analysis of data show that the size of the critical microtubule nucleus is always tubulin dimers but the assembly pathway differs in the two regimes. truecm

(D. Kuchnir Fygenson), (H. Flyvbjerg), K. Sneppen, (A. Libchaber) and (S. Leibler) truecm

Biological Evolution: Fitness Optimization and the Decay in Extinction Rate truecm

Fossil records indicate that the background extinction rate has decreased since Cambrian time. As pointed out by Raup and Sepkoski, this observation may be a natural consequence of fitness optimization leading to prolonged survival of species through evolutionary time. Based on this view, a challenging task is to find simple mechanisms that lead to fitness optimization and a related decay in extinction rate. We are investigating such a model, where species evolve through punctuated equilibria. We consider two different rules for extinction. The first, which leads to an analytically solvable problem, assumes that a fixed fraction of evolutionary jumps leads to extinctions. The second specifically introduces Darwinian competition - a `survival of the fittest' rule acting among neighbors in a suitably defined ecology. We consider good evolutionary measures for the significance of competition among species. Our work is in contrast to the view of evolution as a self-organized critical phenomenon. truecm

(M. R. Schmidt), (P. Sibani) and P. AlstrÝm


Evolution as a Self-Organized Critical Phenomenon truecm

We present a simple mathematical model of biological macroevolution. The model describes an ecology of adapting, interacting species. The environment of any given species is affected by other evolving species; hence it is not constant in time. The ecology as a whole evolves to a ``self-organized critical'' state where periods of stasis alternate with avalanches of causally connected evolutionary changes. This characteristic intermittent behaviour of natural history, known as ``punctuated equilibrium," thus finds a theoretical explanation as a self-organized critical phenomenon. The evolutionary behavior of single species is intermittent. Also, large bursts of apparently simultaneous evolutionary activity require no external cause. Extinctions of all sizes, including mass extinctions, may be a simple consequence of ecosystem dynamics. Our results are compared with data from the fossil record collected by J. J. Sepkoski, Jr., and others. truecm

K. Sneppen, (P. Bak), (H. Flyvbjerg) and M.H. Jensen


Dynamics in Critical Growth of Biological Systems truecm

An experimental study of dynamics of growth of biological systems has been initiated. Time series of digitized images of a growing fungus colony are recorded, and the morphology of the continuous interface of the growing colony is studied. We see indications of coexistence of structures on all scales: Microscopic structures due to the size of the individual cell, mesoscopic symmetric structures, symmetry-breaking macroscopic structures. truecm

T. Sams, C. Ellegaard, V. Putkaradze, (B. E. Christensen) and (U. Thrane) truecm

Adaptive Performance Networks truecm

One of the most important goals in neuroscience is to understand the way the brain manage to undertake a diversity of tasks. On the neural level the underlying network dynamics is not task specific, and a realistic attempt to explain the brains ability to function must take this into account. In sharp contrast, the traditional artificial neural networks are heavily constrained, and the a priori knowledge of the task is crucial. The structure has to be self-organized rather than by design. Thus to understand the brain, we must understand the principles by which is organizes itself through interactions with the environment. Recently, we have introduced a new class of adaptive networks that by construction are able to function in an changeable environment. Their performance is intimately connected with the adaptive nature. We denote this adaptive performance to emphasize that the dynamics cannot be divided into a learning mode and a retrieving mode as known from traditional artificial neural networks. Our studies follows two directions. One is the relations to physiology and phycology. The other is the use of the network on industrial applications. On the medical side, the point is to extract some important principles for brain functioning. On the network level, we would like to understand the processes of conditioning, and the behaviors like habituation and sensitization. On the industrial side, we are investigating a multitude of possible applications, from control and robotics to analysis and diagnosis. Tests are carried out on computer, but electronic `neurons' are also being built. truecm

P. AlstrÝm, P. Andresén, (P. Bak), K. N. Berntsen, J. Nordfalk, N. Petersen, A. Vallespin Gomez and (D. Stassinopoulos) truecm

Neural Networks in Psychological Testing truecm

A feed-forward neural network has been constructed to recognize hand-drawn patterns in a clinical test of concentration ability. The architecture uses both position and direction sensitivity in the input layer. The resulting network performs significantly better than methods based on ``objective'' criteria for the classification of the patterns. truecm

T. Sams, (P. Laursen) and (L. Eskelinen) truecm

Modeling Interactions between HIV and the Imune System truecm

Antibodies specific for epitopes of HIV glycoprotein gp 120 or gp 41 can inhibit or enhance HIV infection of human cells in vitro. These effects may have significant implications both for the pathogenesis of chronic HIV infection and for vaccine development. A particular puzzling finding in vitro is antibody dependent enhancement at low antibody concentrations while high concentrations of the same antibody inhibit infection.We have proposed a mathematical model that describes how these two processes interact and hereby provide an explanation of the observed enhancement. Simulation results were validated against empirical data from HIV infection of monocytoid (U937) cells in vitro. truecm

(J. Hansen), (J.-E. S. Hansen), O. Lund, E. Mosekilde and (J.O. Nielsen) truecm

Modeling Bone Remodeling truecm

Bone remodeling changes bones mass, architecture, and strength during aging. These changes seem to be accelerated during menopause.We have developed a stochastic simulation model of vertebral trabecular bone remodeling. The model can assist in evaluating the long-term effects of changes in the remodeling process. The results show that a menopause-related doubling of the activation frequency causes a transient, mainly reversible bone loss. If the menopause is accompanied by an increase in both activation frequency and resorption depth, then the resulting bone loss will be more pronounced and with a larger part being related with irreversible perforations. As part of the same study we have designed a computer program for direct measurement of 3D connectivity density in iliac crest bone sections as used for conventional histomorphometry. truecm

(R. Boyce), E. Mosekilde, (Li. Mosekilde) and J.S. Thomsen truecm

Modeling Pulsatile Insulin Secretion truecm

The relationship between the in vivo insulin secretory responsiveness of the pancreatic -cell to glucose and the flux of glucose through the enzyme glucokinase has been investigated in six subjects with heterozygous glucokinase mutations and in six matched control subjects. In two subjects with glucokinase mutations, which resulted in only a small reduction in enzyme activity, the decrease in insulin secretion was directly proportional to the reduction in the flux of glucose through glucokinase. In four subjects with severe reductions in enzymatic activity, insulin was reduced compared with control subjects, but less than predicted.We have suggested a simple model which can explain the compensatory change in the b-cells for the latter subjects. truecm

(P. Froguel), E. Mosekilde, (K. Polonsky) and (J. Sturis) truecm

Hyperchaos in Micro- and Macrobiological Population Dynamics truecm

We have simulated a variety of growth, competition and selection processes that may arise in interacting populations of bacteria and phages. Our model considers a culture containing several variants of the same bacterium, each sensitive to attacks from a specific phage. The culture grows in a chemostat with continuous supply of nutrients. Depending of the rate of dilution, the model exhibits stable equilibrium, self-sustained oscillations, quasiperiodic behavior, deterministic chaos or hyperchaos. This last form of dynamics is characterized by two or more positive Lyapunov exponents. We have also studied the dynamics of a simple model of an aquatic ecosystem with four different species (bacteria, algae, zooplankton and fish) and three different dead pools (detritus and accessible nutrients in the water column and nutrients bound to the sediment). truecm

M. Barfred, M. Liberoth and E. Mosekilde

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Next: Chemical reaction-diffusion systems Up: RESEARCH PROJECTS Previous: Fractalscritical phenomena

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