A dynamic role for HDAC7 in MEF2-mediated muscle differentiation

The overlapping expression profile of MEF2 and the class-II histone deacetylase, HDAC7, led us to investigate the functional interaction and relationship between these regulatory proteins. HDAC7 expression inhibits the activity of MEF2 (-A, -C, and -D), and in contrast MyoD and Myogenin activities are not affected. Glutathione S-transferase pulldown and immunoprecipitation demonstrate that the repression mechanism involves direct interactions between MEF2 proteins and HDAC7 and is associated with the ability of MEF2 to interact with the N-terminal 121 amino acids of HDAC7 that encode repression domain 1. The MADS domain of MEF2 mediates the direct interaction of MEF2 with HDAC7, MEF2 inhibition by HDAC7 is dependent on the N-terminal repression domain and surprisingly does not involve the C-terminal deacetylase domain. HDAC7 interacts with CtBP and other class-I and -II HDACs suggesting that silencing of MEF2 activity involves corepressor recruitment. Furthermore, we show that induction of muscle differentiation by serum withdrawal leads to the translocation of HDAC7 from the nucleus into the cytoplasm. This work demonstrates that HDAC7 regulates the function of MEF2 proteins and suggests that this class-II HDAC regulates this important transcriptional (and pathophysiological) target in heart and muscle tissue. The nucleocytoplasmic trafficking of HDAC7 and other class-II HDACs during myogenesis provides an ideal mechanism for the regulation of HDAC targets during mammalian development and differentiation.

A generalised dynamic model for char particle gasification with structure evolution and peripheral fragmentation

A generalised model for the prediction of single char particle gasification dynamics, accounting for multi-component mass transfer with chemical reaction, heat transfer, as well as structure evolution and peripheral fragmentation is developed in this paper. Maxwell-Stefan analysis is uniquely applied to both micro and macropores within the framework of the dusty-gas model to account for the bidisperse nature of the char, which differs significantly from the conventional models that are based on a single pore type. The peripheral fragmentation and random-pore correlation incorporated into the model enable prediction of structure/reactivity relationships. The occurrence of chemical reaction within the boundary layer reported by Biggs and Agarwal (Chem. Eng. Sci. 52 (1997) 941) has been confirmed through an analysis of CO/CO2 product ratio obtained from model simulations. However, it is also quantitatively observed that the significance of boundary layer reaction reduces notably with the reduction of oxygen concentration in the flue gas, operational pressure and film thickness. Computations have also shown that in the presence of diffusional gradients peripheral fragmentation occurs in the early stages on the surface, after which conversion quickens significantly due to small particle size. Results of the early commencement of peripheral fragmentation at relatively low overall conversion obtained from a large number of simulations agree well with experimental observations reported by Feng and Bhatia (Energy & Fuels 14 (2000) 297). Comprehensive analysis of simulation results is carried out based on well accepted physical principles to rationalise model prediction. (C) 2001 Elsevier Science Ltd. AH rights reserved.

EphB2 and two of its ligands have dynamic protein expression patterns in the developing olfactory system

Primary olfactory neurons are located in the olfactory neuroepithelium lining the nasal cavity. Their axons converge and form glomeruli with the dendrites of second-order neurons in the olfactory bulb. The molecular basis of primary olfactory axon guidance, targeting and subsequent arborisation is largely unknown. In this study we examined the spatio-temporal expression of the Eph receptor EphB2 and its ligands, ephrin-B1 and ephrin-B2, during development of the rat primary olfactory system. Unlike in other regions of the nervous system where receptor and ligand expression patterns are usually non-overlapping, EphB2, ephrin-B1 and ephrin-B2 were all expressed by primary and second-order olfactory neurons. In the embryonic animal we found that these three proteins had distinct and different expression patterns. EphB2 was first expressed at E18.5 by the perikarya of primary olfactory neurons. In contrast, ephrin-B1 was expressed from E13.5 and was localised to the axons of these cells up to E18.5 but was then restricted to the perikarya. Ephrin-B2, however, was expressed by olfactory ensheathing cells. EphB2, ephrin-B1 and ephrin-B2 were also expressed in the prenatal olfactory bulb and were restricted to the perikarya of mitral cells. In the post-natal olfactory bulb there was a shift in the localisation of both EphB2 and ephrin-B1 to the dendritic arborisations of mitral cells. The dynamic and tightly regulated spatio-temporal expression patterns of EphB2, ephrin-B1 and ephrin-B2 by specific olfactory cell populations suggest that these molecules have the potential to regulate important developmental events in the olfactory system. (C) 2001 Elsevier Science B.V. All rights reserved.

Spatially dynamic expression of Sry in mouse genital ridges

We have studied the spatial dynamics of Sry transcription in the genital ridges of mouse embryos. We find that Sry is expressed in a dynamic wave that emanates from the central and/or anterior regions, extends subsequently to both poles, and ends in the caudal pole. This dynamism may explain the relative positioning of ovarian and testicular tissue seen in ovotestes in mice. Since direct regulatory targets of SRY ought to be expressed in a corresponding or complimentary wave, our observations pave the way for identification of target genes. Sry is expressed in internal cells but not in coelomic surface epithelial cells, indicating that its effect on proliferation of surface cells is achieved non-cell-autonomously. The cellular dynamism of Sry expression revealed in this study thus provides important insights into both the cellular and molecular mode of action of SRY, and how perturbations in Sry expression can lead to anomalies of sexual development. (C) 2001 Wiley-Liss, Inc.

Simulations of thermal Bose fields in the classical limit

We demonstrate that the time-dependent projected Gross-Pitaevskii equation (GPE) derived earlier [M. J. Davis, R. J. Ballagh, and K. Burnett, J. Phys. B 34, 4487 (2001)] can represent the highly occupied modes of a homogeneous, partially-condensed Bose gas. Contrary to the often held belief that the GPE is valid only at zero temperature, we find that this equation will evolve randomized initial wave functions to a state describing thermal equilibrium. In the case of small interaction strengths or low temperatures, our numerical results can be compared to the predictions of Bogoliubov theory and its perturbative extensions. This demonstrates the validity of the GPE in these limits and allows us to assign a temperature to the simulations unambiguously. However, the GPE method is nonperturbative, and we believe it can be used to describe the thermal properties of a Bose gas even when Bogoliubov theory fails. We suggest a different technique to measure the temperature of our simulations in these circumstances. Using this approach we determine the dependence of the condensate fraction and specific heat on temperature for several interaction strengths, and observe the appearance of vortex networks. Interesting behavior near the critical point is observed and discussed.

Dynamic Behavior of the Jahn-Teller distorted Cu(H2O)(6)(2+) ion in Cu2+ doped Cs-2[Zn(H2O)(6)](ZrF6)(2) and the crystal structure of the host lattice

The temperature dependence of the X- and Q-band EPR spectra of Cs-2[Zn(H2O)(6)](ZrF6)(2) containing similar to1% Cu2+ is reported. All three molecular g-values vary with temperature, and their behavior is interpreted using a model in which the potential surface of the Jahn-Teller distorted Cu(H2O)(6)(2+) ion is perturbed by an orthorhombic strain induced by interactions with the surrounding lattice. The strain parameters are significantly smaller than those reported previously for the Cu(H2O)(6)(2+) ion in similar lattices. The temperature dependence of the two higher g-values suggests that in the present compound the lattice interactions change slightly with temperature. The crystal structure of the Cs-2[Zn(H2O)(6)](ZrF6)(2) host is reported, and the geometry of the Zn(H2O)(6)(2+) ion is correlated with lattice strain parameters derived from the EPR spectrum of the guest Cu2+ complex.

Molecular transport in nanopores

Simulation of the transport of methane in cylindrical silica mesopores have been performed using equilibrium and nonequilibrium molecular dynamics (NEMD) as well as dual control volume grand canonical molecular dynamics methods. It is demonstrated that all three techniques yield the same transport coefficient even in the presence of viscous flow. A modified locally averaged density model for viscous flow, combined with consideration of wall slip through a frictional condition, gives a convincing interpretation of the variation of the transport coefficient over a wide range of densities, and for various pore sizes and temperatures. Wall friction coefficients extracted from NEMD simulations are found to be consistent with momentum transfer arguments, and the approach is shown to be more meaningful than the classical slip length concept. (C) 2003 American Institute of Physics.

Molecular dynamics computer simulation of scratch resistance testing of polymers: visualization

Experimental scratch resistance testing provides two numbers: the penetration depth Rp and the healing depth Rh. In molecular dynamics computer simulations, we create a material consisting of N statistical chain segments by polymerization; a reinforcing phase can be included. Then we simulate the movement of an indenter and response of the segments during X time steps. Each segment at each time step has three Cartesian coordinates of position and three of momentum. We describe methods of visualization of results based on a record of 6NX coordinates. We obtain a continuous dependence on time t of positions of each of the segments on the path of the indenter. Scratch resistance at a given location can be connected to spatial structures of individual polymeric chains.

Polymer indentation with mesoscopic molecular dynamics

Indentation tests are used to determine the hardness of a material, e.g., Rockwell, Vickers, or Knoop. The indentation process is empirically observed in the laboratory during these tests; the mechanics of indentation is insufficiently understood. We have performed first molecular dynamics computer simulations of indentation resistance of polymers with a chain structure similar to that of high density polyethylene (HDPE). A coarse grain model of HDPE is used to simulate how the interconnected segments respond to an external force imposed by an indenter. Results include the time-dependent measurement of penetration depth, recovery depth, and recovery percentage, with respect to indenter force, indenter size, and indentation time parameters. The simulations provide results that are inaccessible experimentally, including continuous evolution of the pertinent tribological parameters during the entire indentation process.

Simulating scratch behavior of polymers with mesoscopic molecular dynamics

Part replacement and repair is needed in structures with moving parts because of scratchability and wear. In spite of some accumulation of experimental evidence, scratch resistance is still not well understood. We have applied molecular dynamics to study scratch resistance of amorphous polymeric materials through computer simulations. As a first approach, a coarse grain model was created for high density polyethylene at the mesoscale. We have also extended the traditional approach and used real units rather than reduced units (to our knowledge, for the first time), which enable an improved quantification of simulation results. The obtained results include analysis of penetration depth, residual depth and recovery percentage related to indenter force and size. Our results show there is a clear effect from these parameters on the tribological properties. We also discuss a "crooked smile" effect on the scratched surface and the reasons for its appearance.

Evaluation of the respiratory motion effect in small animal PET images with GATE Monte Carlo simulations

The rapid growth in genetics and molecular biology combined with the development of techniques for genetically engineering small animals has led to increased interest in in vivo small animal imaging. Small animal imaging has been applied frequently to the imaging of small animals (mice and rats), which are ubiquitous in modeling human diseases and testing treatments. The use of PET in small animals allows the use of subjects as their own control, reducing the interanimal variability. This allows performing longitudinal studies on the same animal and improves the accuracy of biological models. However, small animal PET still suffers from several limitations. The amounts of radiotracers needed, limited scanner sensitivity, image resolution and image quantification issues, all could clearly benefit from additional research. Because nuclear medicine imaging deals with radioactive decay, the emission of radiation energy through photons and particles alongside with the detection of these quanta and particles in different materials make Monte Carlo method an important simulation tool in both nuclear medicine research and clinical practice. In order to optimize the quantitative use of PET in clinical practice, data- and image-processing methods are also a field of intense interest and development. The evaluation of such methods often relies on the use of simulated data and images since these offer control of the ground truth. Monte Carlo simulations are widely used for PET simulation since they take into account all the random processes involved in PET imaging, from the emission of the positron to the detection of the photons by the detectors. Simulation techniques have become an importance and indispensable complement to a wide range of problems that could not be addressed by experimental or analytical approaches.

Monte Carlo modeling and simulations of the High Definition (HD120) micro MLC and validation against measurements for a 6 MV beam

Purpose: The most recent Varian® micro multileaf collimator(MLC), the High Definition (HD120) MLC, was modeled using the BEAMNRCMonte Carlo code. This model was incorporated into a Varian medical linear accelerator, for a 6 MV beam, in static and dynamic mode. The model was validated by comparing simulated profiles with measurements. Methods: The Varian® Trilogy® (2300C/D) accelerator model was accurately implemented using the state-of-the-art Monte Carlo simulation program BEAMNRC and validated against off-axis and depth dose profiles measured using ionization chambers, by adjusting the energy and the full width at half maximum (FWHM) of the initial electron beam. The HD120 MLC was modeled by developing a new BEAMNRC component module (CM), designated HDMLC, adapting the available DYNVMLC CM and incorporating the specific characteristics of this new micro MLC. The leaf dimensions were provided by the manufacturer. The geometry was visualized by tracing particles through the CM and recording their position when a leaf boundary is crossed. The leaf material density and abutting air gap between leaves were adjusted in order to obtain a good agreement between the simulated leakage profiles and EBT2 film measurements performed in a solid water phantom. To validate the HDMLC implementation, additional MLC static patterns were also simulated and compared to additional measurements. Furthermore, the ability to simulate dynamic MLC fields was implemented in the HDMLC CM. The simulation results of these fields were compared with EBT2 film measurements performed in a solid water phantom. Results: Overall, the discrepancies, with and without MLC, between the opened field simulations and the measurements using ionization chambers in a water phantom, for the off-axis profiles are below 2% and in depth-dose profiles are below 2% after the maximum dose depth and below 4% in the build-up region. On the conditions of these simulations, this tungsten-based MLC has a density of 18.7 g cm− 3 and an overall leakage of about 1.1 ± 0.03%. The discrepancies between the film measured and simulated closed and blocked fields are below 2% and 8%, respectively. Other measurements were performed for alternated leaf patterns and the agreement is satisfactory (to within 4%). The dynamic mode for this MLC was implemented and the discrepancies between film measurements and simulations are within 4%. Conclusions: The Varian® Trilogy® (2300 C/D) linear accelerator including the HD120 MLC was successfully modeled and simulated using the Monte CarloBEAMNRC code by developing an independent CM, the HDMLC CM, either in static and dynamic modes.

Enhanced Race-to-halt: a leakage-aware energy management approach for dynamic priority systems

With progressing CMOS technology miniaturization, the leakage power consumption starts to dominate the dynamic power consumption. The recent technology trends have equipped the modern embedded processors with the several sleep states and reduced their overhead (energy/time) of the sleep transition. The dynamic voltage frequency scaling (DVFS) potential to save energy is diminishing due to efficient (low overhead) sleep states and increased static (leakage) power consumption. The state-of-the-art research on static power reduction at system level is based on assumptions that cannot easily be integrated into practical systems. We propose a novel enhanced race-to-halt approach (ERTH) to reduce the overall system energy consumption. The exhaustive simulations demonstrate the effectiveness of our approach showing an improvement of up to 8 % over an existing work.

Optimising and adapting the QoS of a dynamic set of inter-dependent tasks

Due to the growing complexity and adaptability requirements of real-time systems, which often exhibit unrestricted Quality of Service (QoS) inter-dependencies among supported services and user-imposed quality constraints, it is increasingly difficult to optimise the level of service of a dynamic task set within an useful and bounded time. This is even more difficult when intending to benefit from the full potential of an open distributed cooperating environment, where service characteristics are not known beforehand and tasks may be inter-dependent. This paper focuses on optimising a dynamic local set of inter-dependent tasks that can be executed at varying levels of QoS to achieve an efficient resource usage that is constantly adapted to the specific constraints of devices and users, nature of executing tasks and dynamically changing system conditions. Extensive simulations demonstrate that the proposed anytime algorithms are able to quickly find a good initial solution and effectively optimise the rate at which the quality of the current solution improves as the algorithms are given more time to run, with a minimum overhead when compared against their traditional versions.

Capacity sharing and stealing in dynamic server-based real-time systems

This paper proposes a dynamic scheduler that supports the coexistence of guaranteed and non-guaranteed bandwidth servers to efficiently handle soft-tasks’ overloads by making additional capacity available from two sources: (i) residual capacity allocated but unused when jobs complete in less than their budgeted execution time; (ii) stealing capacity from inactive non-isolated servers used to schedule best-effort jobs. The effectiveness of the proposed approach in reducing the mean tardiness of periodic jobs is demonstrated through extensive simulations. The achieved results become even more significant when tasks’ computation times have a large variance.