A Stochastic Finite Element Model for the Dynamics of Globular Macromolecules

We describe a novel coarse grained simulation method for modelling the dynamics of globular macromolecules, such as proteins. The macromolecule is treated as a viscoelastic continuum that is subject to thermal fluctuations. The model includes a non-linear treatment of elasticity and viscosity with thermal noise that is solved using finite element analysis. We have validated the method by demonstrating that the model provides average kinetic and potential energies that are in agreement with the classical equipartition theorem. In addition, we have performed Fourier analysis on the simulation trajectories obtained for a series of linear beams to confirm that the correct average energies are present in the first two Fourier bending modes. We have then used the new modelling method to simulate the thermal fluctuations of a representative protein over 500ns timescales. Using reasonable parameters for the material properties, we have demonstrated that the overall deformation of the biomolecule is consistent with the results obtained for proteins in general from atomistic molecular dynamics simulations

Composition, abundance and seasonality of fish larvae in the mouth of Durban harbour, KwaZulu-Natal, South Africa

Ichthyoplankton samples were collected every six weeks at night on consecutive ebb and flood tides over an 18-month period (June 1991–December 1992) at surface, middle and bottom depths near the entrance of Durban Harbour to investigate the composition, abundance, seasonality and developmental stages of fish larvae in the harbour. In all, 8 797 fish larvae, representing 144 species and 64 families were collected. The Clupeidae and Gobiidae were the dominant families, representing 30 and 15% of the total catch respectively. The most abundant larvae were the blueline herring Herklotsichthys quadrimaculatus, which contributed 29.7% of the total catch. Larvae of estuarine-independent species dominated the total catch, both in terms of density (78%) and number of species (81%). In all, 28 species dependent on estuaries at some stage in their life cycle were recorded; of these 13 were species totally dependent on estuaries. Temperature and salinity accounted for 31% of the variation in larval densities of estuarine-dependent species. Turbidity was a significant variable for estuarineindependent species, larval densities of the abundant species being negatively correlated to turbidity. Larvaldensity peaked mainly in August 1992 (winter), with a mean larval density of 118 larvae.100m-3. Larvae of estuarine-associated species were mainly at the flexion and postflexion developmental stages, whereas most larvaeof estuarine-independent species were at preflexion and flexion stages. Larval densities of certain estuarineassociated species (e.g. Argyrosomus sp.) were significantly higher in bottom samples, mainly on flood tides butalso on ebb tides, suggesting that selective tidal stream transport is a recruitment mechanism used by these species. The impact of harbour development is shown by the dominant marine component of the larval fish assemblage in the harbour. However, despite the seminatural estuarine environment of Durban Harbour, the high species diversity of fish larvae in the system indicates that the harbour is in a relatively good ecological condition

The future of biomolecular simulation in the pharmaceutical industry: what we can learn from aerodynamics modelling and weather prediction. Part 1. understanding the physical and computational complexity of in silico drug design

The predictive power of simulation has become embedded in the infrastructure of modern economies. Computer-aided design is ubiquitous throughout industry. In aeronautical engineering, built infrastructure and materials manufacturing, simulations are routinely used to compute the performance of potential designs before construction. The ability to predict the behaviour of products is a driver of innovation by reducing the cost barrier to new designs, but also because radically novel ideas can be piloted with relatively little risk. Accurate weather forecasting is essential to guide domestic and military flight paths, and therefore the underpinning simulations are critical enough to have implications for national security. However, in the pharmaceutical and biotechnological industries, the application of computer simulations remains limited by the capabilities of the technology with respect to the complexity of molecular biology and human physiology. Over the last 30 years, molecular-modelling tools have gradually gained a degree of acceptance in the pharmaceutical industry. Drug discovery has begun to benefit from physics-based simulations. While such simulations have great potential for improved molecular design, much scepticism remains about their value. The motivations for such reservations in industry and areas where simulations show promise for efficiency gains in preclinical research are discussed. In this, the first of two complementary papers, the scientific and technical progress that needs to be made to improve the predictive power of biomolecular simulations, and how this might be achieved, is firstly discussed (Part 1). In Part 2, the status of computer simulations in pharma is contrasted with aerodynamics modelling and weather forecasting, and comments are made on the cultural changes needed for equivalent computational technologies to become integrated into life-science industries

Three-dimensional assessment of impingement risk in geometrically parameterised hips compared with clinical measures

Abnormal bony morphology is a factor implicated in hip joint soft tissue damage and an increased lifetime risk of osteoarthritis. Standard two-dimensional radiographic measurements for diagnosis of hip deformities, such as cam deformities on the femoral neck, do not capture the full joint geometry and are not indicative of symptomatic damage. In this study, a three-dimensional geometric parameterisation system was developed to capture key variations in the femur and acetabulum of subjects with clinically diagnosed cam deformity. The parameterisation was performed for Computed Tomography scans of 20 patients (10 female, 10 male). Novel quantitative measures of cam deformity were taken and used to assess differences in morphological deformities between males and females. The parametric surfaces matched the more detailed, segmented hip bone geometry with low fitting error. The quantitative severity measures captured both the size and position of cams, and distinguished between cam and control femurs. The precision of the measures was sufficient to identify differences between subjects that could not be seen with the sole use of two-dimensional imaging. In particular, cams were found to be more superiorly located in males than in females. As well as providing a means to distinguish between subjects more clearly, the new geometric hip parameterisation facilitates the flexible and rapid generation of a range of realistic hip geometries including cams. When combined with material property models, these stratified cam shapes can be used for further assessment of the effect of the geometric variation under impingement conditions

Molecular cluster decay viewed as escape from a potential of mean force

We show that evaporation from a quasistable molecular cluster may be treated as a kinetic problem involving the stochastically driven escape of a molecule from a potential of mean force. We derive expressions for the decay rate, and a relationship between the depth of the potential and the change in system free energy upon loss of a molecule from the cluster. This establishes a connection between kinetic and thermodynamic treatments of evaporation, but also reveals differences in the prefactor in the rate expression. We perform constant energy molecular dynamics simulations of cluster dynamics to calculate potentials of mean force, friction coefficients and effective temperatures for use in the kinetic analysis, and to compare the results with the directly observed escape rates. We also use the simulations to estimate the escape rates by a probabilistic analysis. It is much more efficient to calculate the decay rate by the methods we have developed than it is to monitor escape directly, making these approaches potentially useful for the assessment of molecular cluster stability. (C) 2004 American Institute of Physics

Establishing comprehensive oral assessments for children with safeguarding concerns.

The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input

A partial skeleton of an enantiornithine bird from the early Cretaceous of northwestern China

Although recent discoveries from Lower Cretaceous sediments in northeastern China have greatly improved our understanding of the initial stages of avian diversification in eastern Asia, the early evolution of Aves elsewhere on the continent remains poorly understood. In 2004, a collaborative field effort directed by personnel from the Chinese Academy of Geological Sciences and Carnegie Museum of Natural History recovered multiple partial to nearly complete avian skeletons from outcrops of the Lower Cretaceous Xiagou Formation exposed in the Changma Basin of northwestern Gansu Province, China. Here we describe a thrush-sized partial skeleton comprised of a fragmentary pelvic girdle and largely complete hind limbs. A phylogenetic analysis of 20 avian ingroup taxa and 169 anatomical characters places the specimen in Enantiomithes, and within that clade, in Enenantiomithes. When coupled with additional recent discoveries from the Changma Basin, the new skeleton improves our understanding of early avian evolution and diversification in central Asia

Inclusive and Direct Photons in S + Au Central Collisions at 200A GeV/c

A hadron and string cascade model, JPCIAE, which is based on LUND string model, PYTHIA event generator especially, is used to study both inclusive photon production and direct photon production in 200A GeV S + Au central collisions. The model takes into account the photon production from the partonic QCD scattering process, the hadronic final-state interaction, and the hadronic decay and deals with them consistently. The results of JPCIAE model reproduce successfully both the WA93 data of low p_T inclusive photon distribution and the WA80 data of transverse momentum dependent upper limit of direct photon. The photon production from different decay channels is investigated for both direct and inclusive photons. We have discussed the effects of the partonic QCD scattering and the hadronic final-state interaction on direct photon production as well.Comment: 6 pages with 5 figure

Kinetic stability of complex molecular clusters

This investigation is concerned with modeling the evaporation, or decay, of n-nonane molecular clusters. We use a unique cluster decay model that was first developed to estimate the decay time scale of argon clusters using molecular-dynamics simulations. In this study we seek to enhance the model so that it represents a more complex cluster decay dynamic, suitable for n-nonane clusters. Experimental measurements of nucleation rates of n-nonane droplets have been used to deduce the rate at which a molecule escapes from the cluster. Typically for an n-nonane cluster containing 40 molecules, at an experimental temperature of 225 K, the empirical decay time, which is the inverse of the decay rate, is estimated to be 50 ns. For this time scale, the direct observation of n-nonane cluster decay from a molecular-dynamics trajectory is not feasible, since decay events are so rare. However, the cluster decay model uses a combination of molecular dynamics and stochastic dynamics in order to resolve the problem associated with long decay time scales. The model is based on a Langevin treatment that views cluster decay as single-particle escape from a confining potential of mean force. It is used to predict kinetic decay times of n-nonane clusters. We discover this result differs significantly from a classically derived decay time scale determined from a continuum thermodynamic treatment of the population balance equations of clusters. However, the dynamically generated results obtained from the kinetic decay model compare more favorably than the classical results with the empirical decay times that are deduced from experimental measurements of n-nonane clusters. (c) 2006 American Institute of Physics

Rethinking how external pressure can suppress dendrites in lithium metal batteries

We offer an explanation for how dendrite growth can be inhibited when Li metal pouch cells are subjected to external loads, even for cells using soft, thin separators. We develop a contact mechanics model for tracking Li surface and sub-surface stresses where electrodes have realistically (micron-scale) rough surfaces. Existing models examine a single, micron-scale Li metal protrusion under a fixed local current density that presses more or less conformally against a separator or stiff electrolyte. At the larger, sub-mm scales studied here, contact between the Li metal and the separator is heterogeneous and far from conformal for surfaces with realistic roughness: the load is carried at just the tallest asperities, where stresses reach tens of MPa, while most of the Li surface feels no force at all. Yet, dendrite growth is suppressed over the entire Li surface. To explain this dendrite suppression, our electrochemical/mechanics model suggests that Li avoids plating at the tips of growing Li dendrites if there is sufficient local stress; that local contact stresses there may be high enough to close separator pores so that incremental Li+ ions plate elsewhere; and that creep ensures that Li protrusions are gradually flattened. These mechanisms cannot be captured by single-dendrite-scale analyses