Differential effects of ERK and p38 signaling in BMP-2 stimulated hypertrophy of cultured chick sternal chondrocytes

Background During endochondral bone formation, the hypertrophy of chondrocytes is accompanied by selective expression of several genes including type X collagen and alkaline phosphatase. This expression is stimulated by inducers including BMPs and ascorbate. A 316 base pair region of the type X collagen (Col X) promoter has been previously characterized as the site required for BMP regulation. The intent of this study was to examine the role of Mitogen Activated Protein (MAP) and related kinase pathways in the regulation of Col X transcription and alkaline phosphatase activity in pre-hypertrophic chick chondrocytes. Results Using a luciferase reporter regulated by the BMP-responsive region of the type X collagen promoter, we show that promoter activity is increased by inhibition of extra-cellular signal regulated kinases 1 or 2 (ERK1/2). In contrast the ability of BMP-2 to induce alkaline phosphatase activity is little affected by ERK1/2 inhibition. The previously demonstrated stimulatory affect of p38 on Col X was shown to act specifically at the BMP responsive region of the promoter. The inhibitory effect of the ERK1/2 pathway and stimulatory effect of the p38 pathway on the Col X promoter were confirmed by the use of mutant kinases. Inhibition of upstream kinases: protein kinase C (PKC) and phosphatidylinositol 3-(PI3) kinase pathways increased basal Col X activity but had no effect on the BMP-2 induced increase. In contrast, ascorbate had no effect on the BMP-2 responsive region of the Col X promoter nor did it alter the increase in promoter activity induced by ERK1/2 inhibition. The previously shown increase in alkaline phosphatase activity induced by ascorbate was not affected by any kinase inhibitors examined. However some reduction in the alkaline phosphatase activity induced by the combination of BMP-2 and ascorbate was observed with ERK1/2 inhibition. Conclusion Our results demonstrate that ERK1/2 plays a negative role while p38 plays a positive role in the BMP-2 activated transcription of type X collagen. This regulation occurs specifically at the BMP-2 responsive promoter region of Col X. Ascorbate does not modulate Col X at this region indicating that BMP-2 and ascorbate exert their action on chondrocyte hypertrophy via different transcriptional pathways. MAP kinases seem to have only a modest effect on alkaline phosphatase when activity is induced by the combination of both BMP-2 and ascorbate

Granular packings with moving side walls

The effects of movement of the side walls of a confined granular packing are studied by discrete element, molecular dynamics simulations. The dynamical evolution of the stress is studied as a function of wall movement both in the direction of gravity as well as opposite to it. For all wall velocities explored, the stress in the final state of the system after wall movement is fundamentally different from the original state obtained by pouring particles into the container and letting them settle under the influence of gravity. The original packing possesses a hydrostatic-like region at the top of the container which crosses over to a depth-independent stress. As the walls are moved in the direction opposite to gravity, the saturation stress first reaches a minimum value independent of the wall velocity, then increases to a steady-state value dependent on the wall-velocity. After wall movement ceases and the packing reaches equilibrium, the stress profile fits the classic Janssen form for high wall velocities, while it has some deviations for low wall velocities. The wall movement greatly increases the number of particle-wall and particle-particle forces at the Coulomb criterion. Varying the wall velocity has only small effects on the particle structure of the final packing so long as the walls travel a similar distance.Comment: 11 pages, 10 figures, some figures in colo

Projection Postulate and Atomic Quantum Zeno Effect

The projection postulate has been used to predict a slow-down of the time evolution of the state of a system under rapidly repeated measurements, and ultimately a freezing of the state. To test this so-called quantum Zeno effect an experiment was performed by Itano et al. (Phys. Rev. A 41, 2295 (1990)) in which an atomic-level measurement was realized by means of a short laser pulse. The relevance of the results has given rise to controversies in the literature. In particular the projection postulate and its applicability in this experiment have been cast into doubt. In this paper we show analytically that for a wide range of parameters such a short laser pulse acts as an effective level measurement to which the usual projection postulate applies with high accuracy. The corrections to the ideal reductions and their accumulation over n pulses are calculated. Our conclusion is that the projection postulate is an excellent pragmatic tool for a quick and simple understanding of the slow-down of time evolution in experiments of this type. However, corrections have to be included, and an actual freezing does not seem possible because of the finite duration of measurements.Comment: 25 pages, LaTeX, no figures; to appear in Phys. Rev.

Onset of fluidization in vertically shaken granular material

When granular material is shaken vertically one observes convection, surface fluidization, spontaneous heap formation and other effects. There is a controversial discussion in literature whether there exists a threshold for the Froude number $\Gamma=A_0\omega_0^2/g$ below which these effects cannot be observed anymore. By means of theoretical analysis and computer simulation we find that there is no such single threshold. Instead we propose a modified criterion which coincides with critical Froude number $\Gamma_c=1$ for small driving frequency $\omega_0$.Comment: 7 pages, 5 figure

The reversible polydisperse Parking Lot Model

We use a new version of the reversible Parking Lot Model to study the compaction of vibrated polydisperse media. The particle sizes are distributed according to a truncated power law. We introduce a self-consistent desorption mechanism with a hierarchical initialization of the system. In this way, we approach densities close to unity. The final density depends on the polydispersity of the system as well as on the initialization and will reach a maximum value for a certain exponent in the power law.Comment: 7 pages, Latex, 12 figure

Equivalent classes of closed three-level systems

Published versio

Phenomenological glass model for vibratory granular compaction

A model for weakly excited granular media is derived by combining the free volume argument of Nowak et al. [Phys. Rev. E 57, 1971 (1998)] and the phenomenological model for supercooled liquids of Adam and Gibbs [J. Chem. Phys. 43, 139 (1965)]. This is made possible by relating the granular excitation parameter \Gamma, defined as the peak acceleration of the driving pulse scaled by gravity, to a temperature-like parameter \eta(\Gamma). The resulting master equation is formally identical to that of Bouchaud's trap model for glasses [J. Phys. I 2, 1705 (1992)]. Analytic and simulation results are shown to compare favourably with a range of known experimental behaviour. This includes the logarithmic densification and power spectrum of fluctuations under constant \eta, the annealing curve when \eta is varied cyclically in time, and memory effects observed for a discontinuous shift in \eta. Finally, we discuss the physical interpretation of the model parameters and suggest further experiments for this class of systems.Comment: 2 references added; some figure labels tweaked. To appear in PR

The UK risk assessment scheme for all non-native species

1. A pest risk assessment scheme, adapted from the EPPO (European and Mediterranean Plant Protection Organisation) scheme, was developed to assess the risks posed to UK species, habitats and ecosystems by non-native taxa. 2. The scheme provides a structured framework for evaluating the potential for non-native organisms, whether intentional or unintentional introductions, to enter, establish, spread and cause significant impacts in all or part of the UK. Specialist modules permit the relative importance of entry pathways, the vulnerability of receptors and the consequences of policies to be assessed and appropriate risk management options to be selected. Spreadsheets for summarising the level of risk and uncertainty, invasive attributes and economic impact were created. In addition, new methods for quantifying economic impact and summarising risk and uncertainty were explored. 3. Although designed for the UK, the scheme can readily be applied elsewhere

Laser ablation loading of a radiofrequency ion trap

The production of ions via laser ablation for the loading of radiofrequency (RF) ion traps is investigated using a nitrogen laser with a maximum pulse energy of 0.17 mJ and a peak intensity of about 250 MW/cm^2. A time-of-flight mass spectrometer is used to measure the ion yield and the distribution of the charge states. Singly charged ions of elements that are presently considered for the use in optical clocks or quantum logic applications could be produced from metallic samples at a rate of the order of magnitude 10^5 ions per pulse. A linear Paul trap was loaded with Th+ ions produced by laser ablation. An overall ion production and trapping efficiency of 10^-7 to 10^-6 was attained. For ions injected individually, a dependence of the capture probability on the phase of the RF field has been predicted. In the experiment this was not observed, presumably because of collective effects within the ablation plume.Comment: submitted to Appl. Phys. B., special issue on ion trappin

Slow relaxation due to optimization and restructuring: Solution on a hierarchical lattice

Motivated by the large strain shear of loose granular materials we introduced a model which consists of consecutive optimization and restructuring steps leading to a self organization of a density field. The extensive connections to other models of statistical phyics are discussed. We investigate our model on a hierarchical lattice which allows an exact asymptotic renormalization treatment. A surprisingly close analogy is observed between the simulation results on the regular and the hierarchical lattices. The dynamics is characterized by the breakdown of ergodicity, by unusual system size effects in the development of the average density as well as by the age distribution, the latter showing multifractal properties.Comment: 11 pages, 7 figures revtex, submitted to PRE see also: cond-mat/020920