The Dynamic Behavior of Individual Microtubules Associated with Chromosomes In Vitro

Mitotic movements of chromosomes are usually coupled to the elongation and shortening of the microtubules to which they are bound. The lengths of kinetochore-associated microtubules change by incorporation or loss of tubulin subunits, principally at their chromosome-bound ends. We have reproduced aspects of this phenomenon in vitro, using a real-time assay that displays directly the movements of individual chromosome-associated microtubules as they elongate and shorten. Chromosomes isolated from cultured Chinese hamster ovary cells were adhered to coverslips and then allowed to bind labeled microtubules. In the presence of tubulin and GTP, these microtubules could grow at their chromosome-bound ends, causing the labeled segments to move away from the chromosomes, even in the absence of ATP. Sometimes a microtubule would switch to shortening, causing the direction of movement to change abruptly. The link between a microtubule and a chromosome was mechanically strong; 15 pN of tension was generally insufficient to detach a microtubule, even though it could add subunits at the kinetochore–microtubule junction. The behavior of the microtubules in vitro was regulated by the chromosomes to which they were bound; the frequency of transitions from polymerization to depolymerization was decreased, and the speed of depolymerization-coupled movement toward chromosomes was only one-fifth the rate of shortening for microtubules free in solution. Our results are consistent with a model in which each microtubule interacts with an increasing number of chromosome-associated binding sites as it approaches the kinetochore.     

Steady-State Kinetic Modeling Constrains Cellular Resting States and Dynamic Behavior

A defining characteristic of living cells is the ability to respond dynamically to external stimuli while maintaining homeostasis under resting conditions. Capturing both of these features in a single kinetic model is difficult because the model must be able to reproduce both behaviors using the same set of molecular components. Here, we show how combining small, well-defined steady-state networks provides an efficient means of constructing large-scale kinetic models that exhibit realistic resting and dynamic behaviors. By requiring each kinetic module to be homeostatic (at steady state under resting conditions), the method proceeds by (i) computing steady-state solutions to a system of ordinary differential equations for each module, (ii) applying principal component analysis to each set of solutions to capture the steady-state solution space of each module network, and (iii) combining optimal search directions from all modules to form a global steady-state space that is searched for accurate simulation of the time-dependent behavior of the whole system upon perturbation. Importantly, this stepwise approach retains the nonlinear rate expressions that govern each reaction in the system and enforces constraints on the range of allowable concentration states for the full-scale model. These constraints not only reduce the computational cost of fitting experimental time-series data but can also provide insight into limitations on system concentrations and architecture. To demonstrate application of the method, we show how small kinetic perturbations in a modular model of platelet P2Y₁ signaling can cause widespread compensatory effects on cellular resting states.     

Modeling Studies of Chromatin Fiber Structure as a Function of DNA Linker Length

Chromatin fibers encountered in various species and tissues are characterized by different nucleosome repeat lengths (NRLs) of the linker DNA connecting the nucleosomes. While single cellular organisms and rapidly growing cells with high protein production have short NRL ranging from 160 to 189 bp, mature cells usually have longer NRLs ranging between 190 and 220 bp. Recently, various experimental studies have examined the effect of NRL on the internal organization of chromatin fiber. Here, we investigate by mesoscale modeling of oligonucleosomes the folding patterns for different NRL, with and without linker histone (LH), under typical monovalent salt conditions using both one-start solenoid and two-start zigzag starting configurations. We find that short to medium NRL chromatin fibers (173 to 209 bp) with LH condense into zigzag structures and that solenoid-like features are viable only for longer NRLs (226 bp). We suggest that medium NRLs are more advantageous for packing and various levels of chromatin compaction throughout the cell cycle than their shortest and longest brethren; the former (short NRLs) fold into narrow fibers, while the latter (long NRLs) arrays do not easily lead to high packing ratios due to possible linker DNA bending. Moreover, we show that the LH has a small effect on the condensation of short-NRL arrays but has an important condensation effect on medium-NRL arrays, which have linker lengths similar to the LH lengths. Finally, we suggest that the medium-NRL species, with densely packed fiber arrangements, may be advantageous for epigenetic control because their histone tail modifications can have a greater effect compared to other fibers due to their more extensive nucleosome interaction network.     

Buckling Behavior of Individual and Bundled Microtubules

As the major structural constituent of the cytoskeleton, microtubules (MTs) serve a variety of biological functions that range from facilitating organelle transport to maintaining the mechanical integrity of the cell. Neuronal MTs exhibit a distinct configuration, hexagonally packed bundles of MT filaments, interconnected by MT-associated protein (MAP) tau. Building on our previous work on mechanical response of axonal MT bundles under uniaxial tension, this study is focused on exploring the compression scenarios. Intracellular MTs carry a large fraction of the compressive loads sensed by the cell and therefore, like any other column-like structure, are prone to substantial bending and buckling. Various biological activities, e.g., actomyosin contractility and many pathological conditions are driven or followed by bending, looping, and buckling of MT filaments. The coarse-grained model previously developed in our lab has been used to study the mechanical behavior of individual and bundled in vivo MT filaments under uniaxial compression. Both configurations show tip-localized, decaying, and short-wavelength buckling. This behavior highlights the role of the surrounding cytoplasm and MAP tau on MT buckling behavior, which allows MT filaments to bear much larger compressive forces. It is observed that MAP tau interconnections improve this effect by a factor of two. The enhanced ability of MT bundles to damp buckling waves relative to individual MT filaments, may be interpreted as a self-defense mechanism because it helps axonal MTs to endure harsher environments while maintaining their function. The results indicate that MT filaments in a bundle do not buckle simultaneously implying that the applied stress is not equally shared among the MT filaments, that is a consequence of the nonuniform distribution of MAP tau proteins along the bundle length. Furthermore, from a pathological perspective, it is observed that axonal MT bundles are more vulnerable to failure in compression than tension.     

Behavior as a social construction

Behavior analysis is examined from a social constructionist perspective. Constructionism is first defined and contrasted with a generic positivistic image of science. Behavior analysis, especially the matching law, is then viewed from both perspectives. The actual practice of behavior analysis (as opposed to the philosophy of radical behaviorism) more strongly resembles positivist than constructionist views. This alignment between behavior analysis and positivism emerges more sharply when positivist and constructionist perspectives are compared on the relation between science and music. Charles Rosen has identified how the classical style of musical composition and performance depended on 18th century keyboard technology, and a constructionist view sees the matching law as reflecting mid 20th century technology and culture in much the same way as it sees, say Mozart's 23rd piano concerto, as reflecting late 18th century culture. Behavior analysts, who often behave as though they see the matching law as an objective, impersonal, stable, hard, cold, incontrovertibly true fact, appear more inclined than constructionists to see a fundamental difference between the matching law and Mozart's 23rd piano concerto, to which they would attribute few if any of these characteristics. Possible implications are derived for tolerance in science.     

Spatiotemporal Variation of Mistletoes: a Dynamic Modeling Approach

Mistletoes are common aerial stem-parasites and their seeds are dispersed by fruit-eating birds. In the mutually beneficial relationships between mistletoes and bird species that disperse mistletoes’ seeds, the preference of birds for infected trees influences the spread of mistletoes and the spatiotemporal pattern formation of mistletoes. We formulate a deterministic model to describe the dynamics of mistletoes in an isolated patch containing an arbitrary number of trees. We establish concrete criterions, expressed in terms of the model parameters, for mistletoes establishing in this area. We conduct numerical simulations based on a field study to reinforce and expand our results.     

Fast Pyrolysis Behavior of Banagrass as a Function of Temperature and Volatiles Residence Time in a Fluidized Bed Reactor

A reactor was designed and commissioned to study the fast pyrolysis behavior of banagrass as a function of temperature and volatiles residence time. Four temperatures between 400 and 600°C were examined as well as four residence times between ~1.0 and 10 seconds. Pyrolysis product distributions of bio-oil, char and permanent gases were determined at each reaction condition. The elemental composition of the bio-oils and chars was also assessed. The greatest bio-oil yield was recorded when working at 450°C with a volatiles residence time of 1.4 s, ~37 wt% relative to the dry ash free feedstock (excluding pyrolysis water). The amounts of char (organic fraction) and permanent gases under these conditions are ~4 wt% and 8 wt% respectively. The bio-oil yield stated above is for ''dry'' bio-oil after rotary evaporation to remove solvent, which results in volatiles and pyrolysis water being removed from the bio-oil. The material removed during drying accounts for the remainder of the pyrolysis products. The ''dry'' bio-oil produced under these conditions contains ~56 wt% carbon which is ~40 wt% of the carbon present in the feedstock. The oxygen content of the 450°C, 1.4 s ''dry'' bio-oil is ~38 wt%, which accounts for ~33 wt% of the oxygen in the feedstock. At higher temperature or longer residence time less bio-oil and char is recovered and more gas and light volatiles are produced. Increasing the temperature has a more significant effect on product yields and composition than increasing the volatiles residence time. At 600°C and a volatiles residence time of 1.2 seconds the bio-oil yield is ~21 wt% of the daf feedstock, with a carbon content of 64 wt% of the bio-oil. The bio-oil yield from banagrass is significantly lower than from woody biomass or grasses such as switchgrass or miscanthus, but is similar to barley straw. The reason for the low bio-oil yield from banagrass is thought to be related to its high ash content (8.5 wt% dry basis) and high concentration of alkali and alkali earth metals (totaling ~2.8 wt% relative to the dry feedstock) which are catalytic and increase cracking reactions during pyrolysis.     

Dynamic Modeling of a Non-Uniform Flexible Tail for a Robotic Fish

In this paper, a non-uniform flexible tail of a fish robot was presented and the dynamic model was developed. In this model, the non-uniform flexible tail was modeled by a rotary slender beam. The hydrodynamics forces, including the reactive force and resistive force, were analyzed in order to derive the governing equation. This equation is a fourth-order in space and second-order in time Partial Differential Equation (PDE) of the lateral movement function. The coefficients of this PDE were not constants because of the non-uniform beams, so they were approximated by exponential functions in order to obtain an analytical solution. This solution describes the lateral movement of the flexible tail as a function of material, geometrical and actuator properties. Experiments were then carried out and compared to simulations. It was proved that the proposed model is suitable for predicting the real behavior of fish robots.     

The Concept of Dispositional Regulation of Individual Social Behavior

After a period of relative neglect by psychologists of issues of social motivation and goal-directed behavior (in favor of attending to the person as a "cognizer," or reinforcement-shaped "responder"), it is clear that the preoccupations of Miller, Galanter, & Pribram (1960) a quarter-century ago have been taken up with renewed interest. Current investigators are of many different persuasions—e.g., cognitively oriented theorists concerned with "lay epistemology" (Kruglanski & Klar, 1986), "personologists" interested in person-environment interactions (Little, 1983), psychologists attempting to clarify the structure and components of action (e.g., Brenner, 1980), etc. Readers familiar with the work of Leont'ev (1975) and the translations and discussions of related work (Wertsch, 1979) will know that a concern with goal direction has never been absent from psychology in the USSR.     

Bilateral Regulation as a Behavior Mechanism

1. With the appearance of cybernetics there has been a considerable increase in interest in problems of the regulation of processes in various complex systems, including the biological. In psychology and physiology, experience has been accumulated in the investigation of certain nerve and mental phenomena as regulatory. This has included study of the emotions in the total cycle of neurohumoral regulation, and of voluntary attention in the regulation of activity.     

On the Organization of Individual Differences in Sexual Behavior

SYNOPSIS. Research on the sexual differentiation of mating behaviorhas impeded progress in our understanding of the proximate basesof individual differences in two ways. First, by viewing variationas categorical rather than continuous, and second, by not placingsufficient emphasis on the fact that males and females differgenetically in many vertebrates, environmental contributionsto individual differences cannot be distinguished from geneticcontributions. Just as there are two levels of organizationof sex, so, too, are there two levels of organization of thesexual phenotype. Primary organization is the process of sexualdifferentiation that follows gonadal determination and is manifestas the morphological, physiological and behavioral aspects ofthe sexual phenotype. There is a second, and subsequent, levelof organization, however, that is directly related to primaryorganization and is the basis of individual variation in sexuallydimorphic behaviors. This level can be termed secondary organization.Because individual variation is the substance of evolutionarychange, understanding its organization will require both newparadigms and alternative animal model systems that allow separationof the effects of genes and hormones from environmental andexperiential stimuli. The plasticity of the sexual phenotypeand how each individual emerges from its own unique circumstancesintegrates these different levels of organization. As mightbe predicted, recent research suggests that the relationshipbetween primary and secondary organization and the developmentof individual differences in sociosexual behaviors involvesmore than just sex steroid hormones.     

Modeling polio as a disease of development

Poliomyelitis is a disease which began to appear in epidemic proportions in the late 19th century, paradoxically, just at the time when living conditions and developments in health were transforming enormously for the better. We present a simple age-class model that explains this "disease of development" as a threshold phenomenon. Epidemics arise when improved conditions in hygiene are able to reduce disease transmission of polio amongst children below a critical threshold level. This generates a large susceptible adult population in which, under appropriate conditions, epidemics can propagate. The polio model is analysed in terms of its bifurcation properties and in terms of its non-equilibrium outbreak dynamics.     

Dynamic Behavior of DNA Replication Domains

Like many nuclear processes, DNA replication takes place in distinct domains that are scattered throughout the S-phase nucleus. Recently we have developed a fluorescent double-labeling procedure that allows us to visualize nascent DNA simultaneously with “newborn” DNA that had replicated earlier in the same nucleus during the same S-phase. Using this procedure we have shown that all DNA in a replication domain is replicated within 1 h (Manderset al.,1992,J. Cell Sci.103, 857–862). Here we extend these studies by analyzing the behavior of replication domains on a time scale of less than 1 h. We have carried out a series of double-labeling experiments in which we varied the time interval between nascent DNA and newborn DNA from 0 to 60 min. Subsequently, we determined from the confocal, 3D images the spatial position of replicated DNA domains and identified pairs of nearest neighbor domains containing newborn and nascent DNA, respectively. The distance between the centers of the two domains in a pair gradually increases. Accurate measurements show that domains containing nascent DNA and domains containing newborn DNA gradually separate from each other at a rate that is on the order of 0.5 μm/h. This indicates that either newly synthesized DNA moves away from sites of replication activity or the replication machinery is moving itself. This rate is essentially the same during early and late S-phase.     

Stock Portfolio Structure of Individual Investors Infers Future Trading Behavior

Although the understanding of and motivation behind individual trading behavior is an important puzzle in finance, little is known about the connection between an investor''s portfolio structure and her trading behavior in practice. In this paper, we investigate the relation between what stocks investors hold, and what stocks they buy, and show that investors with similar portfolio structures to a great extent trade in a similar way. With data from the central register of shareholdings in Sweden, we model the market in a similarity network, by considering investors as nodes, connected with links representing portfolio similarity. From the network, we find investor groups that not only identify different investment strategies, but also represent individual investors trading in a similar way. These findings suggest that the stock portfolios of investors hold meaningful information, which could be used to earn a better understanding of stock market dynamics.     

Dynamic Modeling and Experiment of a Fish Robot with a Flexible Tail Fin

This paper presents the dynamic modeling of a flexible tail for a robotic fish. For this purpose firstly, the flexible tail was simplified as a slewing beam actuated by a driving moment. The governing equation of the flexible tail was derived by using the Euler-Bernoulli theory. In this equation, the resistive forces were estimated as a term analogous to viscous damping. Then, the modal analysis method was applied in order to derive an analytical solution of the governing equation, by which the relationship between the driving moment and the lateral movement of the flexible tail was described. Finally, simulations and experiments were carried out and the results were compared to verify the accuracy of the dynamic model. It was proved that the dynamic model of a fish robot with a flexible tail fin well explains the real behavior of robotic fish in underwater environment.     

Dynamic Rheooptical Behavior of Isolated Bovine Cornea

The dynamic Young's modulus E′ and loss modulus E″ were obtained for isolated bovine cornea using a direct-reading dynamic viscoelastometer. Within the temperature range (0-60°C) and frequency range (3.5-110 Hz) studied, both moduli were temperature and frequency independent. The dynamic birefringence of the cornea was measured in a special apparatus designed for this purpose in conjunction with the dynamic viscoelastometer. The stress-optical and strain-optical coefficients as well as the corresponding phase angles were evaluated as a function of temperature and frequency. The strain- and stress-optical coefficients were both temperature and frequency dependent.