Computational modelling of multi-physics and multi-scale processes in parallel

This paper provides an overview of the developing needs for simulation software technologies for the computational modelling of problems that involve combinations of interactions amongst varying physical phenomena over a variety of time and space scales. Computational modelling of such problems requires software tech1nologies that enable the mathematical description of the interacting physical phenomena together with the solution of the resulting suites of equations in a numerically consistent and compatible manner. This functionality requires the structuring of simulation modules for specific physical phenomena so that the coupling can be effectively represented. These multi-physics and multi-scale computations are very compute intensive and the simulation software must operate effectively in parallel if it is to be used in this context. An approach to these classes of multi-disciplinary simulation in parallel is described, with some key examples of application to2 challenging engineering problems.

Low temperature crystal structures of two rhodanine derivatives, 3-amino rhodanine and 3-methyl rhodanine: geometry of the rhodanine ring

Rhodanines (2-thio-4-oxothiazolidines) are synthetic small molecular weight organic molecules with diverse applications in biochemistry, medicinal chemistry, photochemistry, coordination chemistry and industry. The X-ray crystal structure determination of two rhodanine derivatives, namely (I), 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine], C3H4N2OS2, and (II) 3-methylrhodanine [3-methyl-2-thio-4-oxothiazolidine], C4H5NOS2, have been conducted at 100 K. I crystallizes in the monoclinic space group P2(1)/n with unit cell parameters a = 9.662(2), b = 9.234(2), c = 13.384(2) angstrom, beta = 105.425(3)degrees, V = 1151.1(3) angstrom(3), Z = 8 (2 independent molecules per asymmetric unit), density (calculated) = 1.710 mg/m(3), absorption coefficient = 0.815 mm(-1). II crystallizes in the orthorhombic space group Iba2 with unit cell a = 20.117(4), b = 23.449(5), c = 7.852(2) angstrom, V = 3703.9(12) angstrom(3), Z = 24 (three independent molecules per asymmetric unit), density (calculated) = 1.584 mg/m(3), absorption coefficient 0.755 mm(-1). For I in the final refinement cycle the data/restraints/parameter ratios were 2639/0/161, goodness-of-fit on F-2 = 0.934, final R indices [I > 2sigma(I)] were R1 = 0.0299, wR2 = 0.0545 and R indices (all data) R1 = 0.0399, wR2 = 0.0568. The largest difference peak and hole were 0.402 and -0.259 e angstrom(-3). For II in the final refinement cycle the data/restraints/parameter ratios were 3372/1/221, goodness-of-fit on F(2) = 0.950, final R indices [I > 2sigma(I)] were R1 = 0.0407, wR2 = 0.1048 and R indices (all data) R1 = 0.0450, wR2 = 0.1088. The absolute structure parameter = 0.19(9) and largest difference peak and hole 0.934 and -0.301 e angstrom(-3). Details of the geometry of the five molecules (two for I and three for II) and the crystal structures are fully discussed. Corresponding features of the molecular geometry are highly consistent and firmly establish the geometry of the rhodanine

DFT calculations of the structures and vibrational spectra of the [Fe(bpy)(3)](2+) and [Ru(bpy)(3)](2+) complexes

Structures of the [M(bpy)(3)](2+) complexes (M = Fe and Ru) have been calculated at the B3-LYP/DZVP level. IR and Raman spectra were calculated using the optimised geometries, employing a scaled quantum chemical force field, and compared with an earlier normal coordinate analysis of [Ru(bpy)(3) ](2+) which was based upon experimental data alone, and the use of a simplified model. The results of the calculations provide a highly satisfactory fit to the experimental data and the normal coordinate analyses, in terms of potential energy distributions, allow a detailed understanding of the vibrational spectra of both complexes. Evidence is presented for Jahn-Teller distortion in the E-1 MLCT excited state. (C) 2008 Elsevier B.V. All rights reserved.

Long-Term Retrospective Analysis of Mackerel Spawning in the North Sea: A New Time Series and Modeling Approach to CPR Data

We present a unique view of mackerel (Scomber scombrus) in the North Sea based on a new time series of larvae caught by the Continuous Plankton Recorder (CPR) survey from 1948-2005, covering the period both before and after the collapse of the North Sea stock. Hydrographic backtrack modelling suggested that the effect of advection is very limited between spawning and larvae capture in the CPR survey. Using a statistical technique not previously applied to CPR data, we then generated a larval index that accounts for both catchability as well as spatial and temporal autocorrelation. The resulting time series documents the significant decrease of spawning from before 1970 to recent depleted levels. Spatial distributions of the larvae, and thus the spawning area, showed a shift from early to recent decades, suggesting that the central North Sea is no longer as important as the areas further west and south. These results provide a consistent and unique perspective on the dynamics of mackerel in this region and can potentially resolve many of the unresolved questions about this stock

Consistent increase in dimethyl sulphide (DMS) in response to high CO2 in five shipboard bioassays from contrasting NW European waters

The ubiquitous marine trace gas dimethyl sulphide (DMS) comprises the greatest natural source of sulphur to the atmosphere and is a key player in atmospheric chemistry and climate. We explore the short term response of DMS and its algal precursor dimethyl sulphoniopropionate (DMSP) production and cycling to elevated carbon dioxide (CO2) and ocean acidification (OA) in five highly replicated 96 h shipboard bioassay experiments from contrasting sites in NW European shelf waters. In general, the response to OA throughout this region showed little variation, despite encompassing a range of biological and biogeochemical conditions. We observed consistent and marked increases in DMS concentrations relative to ambient controls, and decreases in DMSP concentrations. Quantification of rates of specific DMSP synthesis by phytoplankton and bacterial DMS gross production/consumption suggest algal processes dominated the CO2 response, likely due to a physiological response manifested as increases in direct cellular exudation of DMS and/or DMSP lyase enzyme activities. The variables and rates we report increase our understanding of the processes behind the response to OA. This could provide the opportunity to improve upon mesocosm-derived empirical modelling relationships, and move towards a mechanistic approach for predicting future DMS concentrations.

Consistent increase in dimethyl sulfide (DMS) in response to high CO2 in five shipboard bioassays from contrasting NW European waters

The ubiquitous marine trace gas dimethyl sulfide (DMS) comprises the greatest natural source of sulfur to the atmosphere and is a key player in atmospheric chemistry and climate. We explore the short-term response of DMS production and cycling and that of its algal precursor dimethyl sulfoniopropionate (DMSP) to elevated carbon dioxide (CO₂) and ocean acidification (OA) in five 96 h shipboard bioassay experiments. Experiments were performed in June and July 2011, using water collected from contrasting sites in NW European waters (Outer Hebrides, Irish Sea, Bay of Biscay, North Sea). Concentrations of DMS and DMSP, alongside rates of DMSP synthesis and DMS production and consumption, were determined during all experiments for ambient CO₂ and three high-CO₂ treatments (550, 750, 1000 μatm). In general, the response to OA throughout this region showed little variation, despite encompassing a range of biological and biogeochemical conditions. We observed consistent and marked increases in DMS concentrations relative to ambient controls (110% (28–223%) at 550 μatm, 153% (56–295%) at 750 μatm and 225% (79–413%) at 1000 μatm), and decreases in DMSP concentrations (28% (18–40%) at 550 μatm, 44% (18–64%) at 750 μatm and 52% (24–72%) at 1000 μatm). Significant decreases in DMSP synthesis rate constants (μDMSP, d⁻¹) and DMSP production rates (nmol d⁻¹) were observed in two experiments (7–90% decrease), whilst the response under high CO₂ from the remaining experiments was generally indistinguishable from ambient controls. Rates of bacterial DMS gross consumption and production gave weak and inconsistent responses to high CO₂. The variables and rates we report increase our understanding of the processes behind the response to OA. This could provide the opportunity to improve upon mesocosm-derived empirical modelling relationships and to move towards a mechanistic approach for predicting future DMS concentrations.

Shark personalities? Repeatability of social network traits in a widely distributed predatory fish. Behavioral Ecology and Sociobiology, 68, 1995-2003.

Interest in animal personalities has generated a burgeoning literature on repeatability in individual traits such as boldness or exploration through time or across different contexts. Yet, repeatability can be influenced by the interactive social strategies of individuals, for example, consistent inter-individual variation in aggression is well documented. Previous work has largely focused on the social aspects of repeatability in animal behaviour by testing individuals in dyadic pairings. Under natural conditions, individuals interact in a heterogeneous polyadic network. However, the extent to which there is repeatability of social traits at this higher order network level remains unknown. Here, we provide the first empirical evidence of consistent and repeatable animal social networks. Using a model species of shark, a taxonomic group in which repeatability in behaviour has yet to be described, we repeatedly quantified the social networks of ten independent shark groups across different habitats, testing repeatability in individual network position under changing environments. To understand better the mechanisms behind repeatable social behaviour, we also explored the coupling between individual preferences for specific group sizes and social network position. We quantify repeatability in sharks by demonstrating that despite changes in aggregation measured at the group level, the social network position of individuals is consistent across treatments. Group size preferences were found to influence the social network position of individuals in small groups but less so for larger groups suggesting network structure, and thus, repeatability was driven by social preference over aggregation tendency.

Plug Force Monitoring for the Control and Optimisation of the Thermoforming Process

Thermoforming processes generally employ sheet temperature monitoring as the primary means of process control. In this paper the development of an alternative system that monitors plug force is described. Tests using a prototype device have shown that the force record over a forming cycle creates a unique map of the process operation. Key process features such as the sheet modulus, sheet sag and the timing of the process stages may be readily observed, and the effects of changes in all of the major processing parameters are easily distinguished. Continuous, cycle-to-cycle tests show that the output is consistent and repeatable over a longer time frame, providing the opportunity for development of an on-line process control system. Further testing of the system is proposed.

Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination

Blood-brain barrier (BBB) hyperpermeability in multiple sclerosis (MS) is associated with lesion pathogenesis and has been linked to pathology in microvascular tight junctions (TJs). This study quantifies the uneven distribution of TJ pathology and its association with BBB leakage. Frozen sections from plaque and normal-appearing white matter (NAWM) in 14 cases were studied together with white matter from six neurological and five normal controls. Using single and double immunofluorescence and confocal microscopy, the TJ-associated protein zonula occludens-1 (ZO-1) was examined across lesion types and tissue categories, and in relation to fibrinogen leakage. Confocal image data sets were analysed for 2198 MS and 1062 control vessels. Significant differences in the incidence of TJ abnormalities were detected between the different lesion types in MS and between MS and control white matter. These were frequent in oil-red O (ORO)+ active plaques, affecting 42% of vessel segments, but less frequent in ORO- inactive plaques (23%), NAWM (13%), and normal (3.7%) and neurological controls (8%). A similar pattern was found irrespective of the vessel size, supporting a causal role for diffusible inflammatory mediators. In both NAWM and inactive lesions, dual labelling showed that vessels with the most TJ abnormality also showed most fibrinogen leakage. This was even more pronounced in active lesions, where 41% of vessels in the highest grade for TJ alteration showed severe leakage. It is concluded that disruption of TJs in MS, affecting both paracellular and transcellular paths, contributes to BBB leakage. TJ abnormality and BBB leakage in inactive lesions suggests either failure of TJ repair or a continuing pathological process. In NAWM, it suggests either pre-lesional change or secondary damage. Clinically inapparent TJ pathology has prognostic implications and should be considered when planning disease-modifying therapy

In vitro phototoxicity of 5-aminolevulinic acid and its methyl ester and the influence of barrier properties on their release from a bioadhesive patch.

opical administration of excess exogenous 5-aminolevulinic acid (ALA) leads to selective accumulation of the potent photosensitiser protoporphyrin IX (PpIX) in neoplastic cells, which can then be destroyed by irradiation with visible light. Due to its hydrophilicity, ALA penetrates deep lesions, such as nodular basal cell carcinomas (BCCs) poorly. As a result, more lipophilic esters of ALA have been employed to improve tissue penetration. In this study, the in vitro release of ALA and M-ALA from proprietary creams and novel patch-based systems across normal stratum corneum and a model membrane designed to mimic the abnormal stratum corneum overlying neoplastic skin lesions were investigated. Receiver compartment drug concentrations were compared with the concentrations of each drug producing high levels of PpIX production and subsequent light-induced kill in a model neoplastic cell line (LOX). LOX cells were found to be quite resistant to ALA- and M-ALA-induced phototoxicity. However, drug concentrations achieved in receiver compartments were comparable to those required to induce high levels of cell death upon irradiation in cell lines reported in the literature. Patches released significantly less drug across normal stratum corneum and significantly more across the model membrane. This is of major significance since the selectivity of PDT for neoplastic lesions will be further enhanced by the delivery system. ALA/M-ALA will only be delivered in significant amounts to the abnormal tissue. PpIX will only then accumulate in the neoplastic cells and the normal surrounding tissue will be unharmed upon irradiation.

Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms.

The murine VEGF gene is alternatively transcribed to yield the VEGF120, VEGF164, and VEGF188 isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF164/164 mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF120/120 mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF188/188 mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF164, was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival

The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and adjacent normal tissue samples from 30 patients with colonic and 22 with rectal adenocarcinoma. Individual features and combined profiles were correlated with clinicopathological parameters and patient survival data to assess their prognostic value. Increased AI was significantly associated with increased bcl-2 expression (p

Disabled Children Negotiating School Life: Agency, Difference and Teaching Practice

This paper explores the school experiences of seven 11–14 year old disabled children, and focuses on their agency as they negotiated a complex, changing, and often challenging social world at school where “difference” was experienced in negative ways. The paper draws on ethnographic data from a wider three-year study that explores the influence of school experiences on both disabled and non-disabled children’s identity as they make the transition from primary to secondary school in regular New Zealand schools (although the focus of the present paper is only on the experiences of disabled children). The wider study considers how Maori (indigenous people of Aotearoa/New Zealand) and Pakeha (New Zealanders of NZ European descent) disabled children and their non- disabled matched peers (matched for age, gender and classroom) understand their personal identity, and how factors relating to transition (from primary to secondary school); culture; impairment (in the case of disabled children); social relationships; and school experience impact on children’s identities. Data on Maori children’s school experiences is currently being collected, and is not yet available for inclusion in this paper. On the basis of our observations in schools we will illustrate how disabled children felt and were made to feel different through an array of structural barriers such as separate provision for disabled students, and peer and teacher attitudes to diversity. However, we agree with Davis, Watson, Shakespeare and Corker’s (2003) interpretation that disabled children’s rights and participation at school are also under attack from a “deeper cultural division” (p. 205) in schools based on discourses of difference and normality. While disabled students in our study were trying to actively construct and shape their social and educational worlds, our data also show that teachers and peers have the capacity to either support or supplant these attempts to be part of the group of “all children”. We suggest that finding solutions that support disabled children’s full inclusion and participation at school requires a multi-faceted and systemic approach focused on a pedagogy for diverse learners, and on a consistent and explicitly inclusive policy framework centred on children’s rights.

Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer's disease and vascular dementia: a case-control study

BACKGROUND: Deposition of beta-amyloid in the brains of patients with Alzheimer's disease is thought to precede a chain of events that leads to an inflammatory response by the brain. We postulated that genetic variation in the regulatory region of the gene for the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) leads to increased risk of Alzheimer's disease and vascular dementia. METHODS: A polymorphism in the regulatory region of the TNF-alpha gene was analysed in a case-control study. The polymorphism (C-850T) was typed in 242 patients with sporadic Alzheimer's disease, 81 patients with vascular dementia, 61 stroke patients without dementia, and 235 normal controls. These groups of individuals were also genotyped for the apolipoprotein E polymorphism, and the vascular dementia and stroke groups were typed at the HLA-DR locus. FINDINGS: The distribution of TNF-alpha genotypes in the vascular dementia group differed significantly from that in the stroke and normal control groups, giving an odds ratio of 2.51 (95% CI 1.49-4.21) for the development of vascular dementia for individuals with a CT or TT genotype. Logistic regression analysis indicated that the possession of the T allele significantly increased the risk of Alzheimer's disease associated with carriage of the apolipoprotein E epsilon4 allele (odds ratio 2.73 [1.68-4.44] for those with apolipoprotein E epsilon4 but no TNF-alpha T, vs 4.62 [2.38-8.96] for those with apolipoprotein E epsilon4 and TNF-alpha T; p=0.03). INTERPRETATION: Possession of the TNF-alpha T allele significantly increases the risk of vascular dementia, and increases the risk of Alzheimer's disease associated with apolipoprotein E. Although further research is needed, these findings suggest a potential role for anti-inflammatory therapy in vascular dementia and Alzheimer's disease, and perhaps especially in patients who have had a stroke.

Soluble P-selectin levels during normal pregnancy: a longitudinal study.

Objective: To investigate soluble P-selectin (sP-selectin) levels and platelet parameters in normal pregnant women compared with non-pregnant control subjects. Design: A longitudinal case-control study. Setting: Obstetric outpatient clinic in the Jubilee Maternity Hospital, Belfast. Population: One hundred and twenty normal pregnant women and 41 non-pregnant age matched control subjects. Main outcome measures Plasma sP-selectin as a measure of platelet activation in normal pregnancy. Methods: The plasma concentration of sP-selectin in pregnant women sampled at 12, 20 and 35 weeks of gestation, and, in a subgroup at 3 days post-partum, and non-pregnant controls sampled in parallel, was determined using a commercial quantitative sandwich immunoassay kit. Platelet parameters on each blood sample were also recorded using a SYSMEX SE 9500 analyser. Main outcome measures: Plasma sP-selectin as a measure of platelet activation in normal pregnancy. Results: Soluble P-selectin was significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation, (p