Flux difference splitting for inviscid, real gases with non-equilibrium chemistry

A flux-difference splitting method is presented for the inviscid terms of the compressible flow equations for chemical non-equilibrium gases

An efficient finite difference scheme for three-dimensional, non-equilibrium flows using operator splitting

An efficient finite difference scheme is presented for the inviscid terms of the three-dimensional, compressible flow equations for chemical non-equilibrium gases. This scheme represents an extension and an improvement of one proposed by the author, and includes operator splitting.

Prediction of supercritical flow in open channels

A finite difference scheme based on flux difference splitting is presented for the solution of the one-dimensional shallow water equations in open channels. A linearised problem, analogous to that of Riemann for gas dynamics, is defined and a scheme, based on numerical characteristic decomposition, is presented for obtaining approximate solutions to the linearised problem. The method of upwind differencing is used for the resulting scalar problems, together with a flux limiter for obtaining a second order scheme which avoids non-physical, spurious oscillations. The scheme is applied to a problem of flow in a river whose geometry induces a region of supercritical flow.

A numerical scheme for two-dimensional, open channel flows with non-rectangular geometries

An algorithm based on flux difference splitting is presented for the solution of two-dimensional, open channel flows. A transformation maps a non-rectangular, physical domain into a rectangular one. The governing equations are then the shallow water equations, including terms of slope and friction, in a generalized coordinate system. A regular mesh on a rectangular computational domain can then be employed. The resulting scheme has good jump capturing properties and the advantage of using boundary/body-fitted meshes. The scheme is applied to a problem of flow in a river whose geometry induces a region of supercritical flow.

A stable one-step-ahead predictive control of non-linear systems

In this paper stability of one-step ahead predictive controllers based on non-linear models is established. It is shown that, under conditions which can be fulfilled by most industrial plants, the closed-loop system is robustly stable in the presence of plant uncertainties and input–output constraints. There is no requirement that the plant should be open-loop stable and the analysis is valid for general forms of non-linear system representation including the case out when the problem is constraint-free. The effectiveness of controllers designed according to the algorithm analyzed in this paper is demonstrated on a recognized benchmark problem and on a simulation of a continuous-stirred tank reactor (CSTR). In both examples a radial basis function neural network is employed as the non-linear system model.

Early identification of stimulant treatment responders, partial responders and non-responders using objective measures in children and adolescents with hyperkinetic disorder

Background: The aim of this study was to evaluate stimulant medication response following a single dose of methylphenidate (MPH) in children and young people with hyperkinetic disorder using infrared motion analysis combined with a continuous performance task (QbTest system) as objective measures. The hypothesis was put forward that a moderate testdose of stimulant medication could determine a robust treatment response, partial response and non-response in relation to activity, attention and impulse control measures. Methods: The study included 44 children and young people between the ages of 7-18 years with a diagnosis of hyperkinetic disorder (F90 & F90.1). A single dose-protocol incorporated the time course effects of both immediate release MPH and extended release MPH (Concerta XL, Equasym XL) to determine comparable peak efficacy periods post intake. Results: A robust treatment response with objective measures reverting to the population mean was found in 37 participants (84%). Three participants (7%) demonstrated a partial response to MPH and four participants (9%) were determined as non-responders due to deteriorating activity measures together with no improvements in attention and impulse control measures. Conclusion: Objective measures provide early into prescribing the opportunity to measure treatment response and monitor adverse reactions to stimulant medication. Most treatment responders demonstrated an effective response to MPH on a moderate testdose facilitating a swift and more optimal titration process.

Non-genomic effects of PPARgamma ligands: inhibition of GPVI-stimulated platelet activation

BACKGROUND: Peroxisome proliferator-activated receptor-(gamma) (PPAR(gamma)) is expressed in human platelets although in the absence of genomic regulation in these cells, its functions are unclear. OBJECTIVE: In the present study, we aimed to demonstrate the ability of PPAR(gamma) ligands to modulate collagen-stimulated platelet function and suppress activation of the glycoprotein VI (GPVI) signaling pathway. METHODS: Washed platelets were stimulated with PPAR(gamma) ligands in the presence and absence of PPAR(gamma) antagonist GW9662 and collagen-induced aggregation was measured using optical aggregometry. Calcium levels were measured by spectrofluorimetry in Fura-2AM-loaded platelets and tyrosine phosphorylation levels of receptor-proximal components of the GPVI signaling pathway were measured using immunoblot analysis. The role of PPAR(gamma) agonists in thrombus formation was assessed using an in vitro model of thrombus formation under arterial flow conditions. RESULTS: PPAR(gamma) ligands inhibited collagen-stimulated platelet aggregation that was accompanied by a reduction in intracellular calcium mobilization and P-selectin exposure. PPAR(gamma) ligands inhibited thrombus formation under arterial flow conditions. The incorporation of GW9662 reversed the inhibitory actions of PPAR(gamma) agonists, implicating PPAR(gamma) in the effects observed. Furthermore, PPAR(gamma) ligands were found to inhibit tyrosine phosphorylation levels of multiple components of the GPVI signaling pathway. PPAR(gamma) was found to associate with Syk and LAT after platelet activation. This association was prevented by PPAR(gamma) agonists, indicating a potential mechanism for PPAR(gamma) function in collagen-stimulated platelet activation. CONCLUSIONS: PPAR(gamma) agonists inhibit the activation of collagen-stimulation of platelet function through modulation of early GPVI signalling.

Amyloid-like fibrillogenesis through supramolecular helix-mediated self-assembly of tetrapeptides containing non-coded alpha-aminoisobutyric acid (Aib) and 3-aminobenzoic acid (m-ABA)

Single-crystal X-ray diffraction studies of two terminally protected tetrapeptides Boc-Ile-Aib-Val-m-ABA-OMe (I) and Boc-Ile-Aib-Phe-m-ABA-OMe (II) (Aib = alpha-aminoisobutyric acid; m-ABA = meta-aminobenzoic acid) reveal that they form continuous H-bonded helices through the association of double-bend (type III and I) building blocks. NMR Studies support the existence of the double-bend (type Ill and I) structures of the peptides in solution also. Field emission scanning electron-microscopic (FE-SEM) and high-resolution transmission electron-microscopic (HR-TEM) images of the peptides exhibit amyloid-like fibrils in the solid state. The Congo red-stained fibrils of peptide I and II, observed between crossed polarizers, show green-gold birefringence, a characteristic of amyloid fibrils.

Optimal control of a class of discrete–continuous non-linear systems — decomposition and hierarchical structure

A technique is derived for solving a non-linear optimal control problem by iterating on a sequence of simplified problems in linear quadratic form. The technique is designed to achieve the correct solution of the original non-linear optimal control problem in spite of these simplifications. A mixed approach with a discrete performance index and continuous state variable system description is used as the basis of the design, and it is shown how the global problem can be decomposed into local sub-system problems and a co-ordinator within a hierarchical framework. An analysis of the optimality and convergence properties of the algorithm is presented and the effectiveness of the technique is demonstrated using a simulation example with a non-separable performance index.

Technologies for biological containment of GM and Non-GM crops

International Perspective The development of GM technology continues to expand into increasing numbers of crops and conferred traits. Inevitably, the focus remains on the major field crops of soybean, maize, cotton, oilseed rape and potato with introduced genes conferring herbicide tolerance and/or pest resistance. Although there are comparatively few GM crops that have been commercialised to date, GM versions of 172 plant species have been grown in field trials in 31 countries. European Crops with Containment Issues Of the 20 main crops in the EU there are four for which GM varieties are commercially available (cotton, maize for animal feed and forage, and oilseed rape). Fourteen have GM varieties in field trials (bread wheat, barley, durum wheat, sunflower, oats, potatoes, sugar beet, grapes, alfalfa, olives, field peas, clover, apples, rice) and two have GM varieties still in development (rye, triticale). Many of these crops have hybridisation potential with wild and weedy relatives in the European flora (bread wheat, barley, oilseed rape, durum wheat, oats, sugar beet and grapes), with escapes (sunflower); and all have potential to cross-pollinate fields non-GM crops. Several fodder crops, forestry trees, grasses and ornamentals have varieties in field trials and these too may hybridise with wild relatives in the European flora (alfalfa, clover, lupin, silver birch, sweet chestnut, Norway spruce, Scots pine, poplar, elm, Agrostis canina, A. stolonifera, Festuca arundinacea, Lolium perenne, L. multiflorum, statice and rose). All these crops will require containment strategies to be in place if it is deemed necessary to prevent transgene movement to wild relatives and non-GM crops. Current Containment Strategies A wide variety of GM containment strategies are currently under development, with a particular focus on crops expressing pharmaceutical products. Physical containment in greenhouses and growth rooms is suitable for some crops (tomatoes, lettuce) and for research purposes. Aquatic bioreactors of some non-crop species (algae, moss, and duckweed) expressing pharmaceutical products have been adopted by some biotechnology companies. There are obvious limitations of the scale of physical containment strategies, addressed in part by the development of large underground facilities in the US and Canada. The additional resources required to grow plants underground incurs high costs that in the long term may negate any advantage of GM for commercial productioNatural genetic containment has been adopted by some companies through the selection of either non-food/feed crops (algae, moss, duckweed) as bio-pharming platforms or organisms with no wild relatives present in the local flora (safflower in the Americas). The expression of pharmaceutical products in leafy crops (tobacco, alfalfa, lettuce, spinach) enables growth and harvesting prior to and in the absence of flowering. Transgenically controlled containment strategies range in their approach and degree of development. Plastid transformation is relatively well developed but is not suited to all traits or crops and does not offer complete containment. Male sterility is well developed across a range of plants but has limitations in its application for fruit/seed bearing crops. It has been adopted in some commercial lines of oilseed rape despite not preventing escape via seed. Conditional lethality can be used to prevent flowering or seed development following the application of a chemical inducer, but requires 100% induction of the trait and sufficient application of the inducer to all plants. Equally, inducible expression of the GM trait requires equally stringent application conditions. Such a method will contain the trait but will allow the escape of a non-functioning transgene. Seed lethality (‘terminator’ technology) is the only strategy at present that prevents transgene movement via seed, but due to public opinion against the concept it has never been trialled in the field and is no longer under commercial development. Methods to control flowering and fruit development such as apomixis and cleistogamy will prevent crop-to-wild and wild-to-crop pollination, but in nature both of these strategies are complex and leaky. None of the genes controlling these traits have as yet been identified or characterised and therefore have not been transgenically introduced into crop species. Neither of these strategies will prevent transgene escape via seed and any feral apomicts that form are arguably more likely to become invasives. Transgene mitigation reduces the fitness of initial hybrids and so prevents stable introgression of transgenes into wild populations. However, it does not prevent initial formation of hybrids or spread to non-GM crops. Such strategies could be detrimental to wild populations and have not yet been demonstrated in the field. Similarly, auxotrophy prevents persistence of escapes and hybrids containing the transgene in an uncontrolled environment, but does not prevent transgene movement from the crop. Recoverable block of function, intein trans-splicing and transgene excision all use recombinases to modify the transgene in planta either to induce expression or to prevent it. All require optimal conditions and 100% accuracy to function and none have been tested under field conditions as yet. All will contain the GM trait but all will allow some non-native DNA to escape to wild populations or to non-GM crops. There are particular issues with GM trees and grasses as both are largely undomesticated, wind pollinated and perennial, thus providing many opportunities for hybridisation. Some species of both trees and grass are also capable of vegetative propagation without sexual reproduction. There are additional concerns regarding the weedy nature of many grass species and the long-term stability of GM traits across the life span of trees. Transgene stability and conferred sterility are difficult to trial in trees as most field trials are only conducted during the juvenile phase of tree growth. Bio-pharming of pharmaceutical and industrial compounds in plants Bio-pharming of pharmaceutical and industrial compounds in plants offers an attractive alternative to mammalian-based pharmaceutical and vaccine production. Several plantbased products are already on the market (Prodigene’s avidin, β-glucuronidase, trypsin generated in GM maize; Ventria’s lactoferrin generated in GM rice). Numerous products are in clinical trials (collagen, antibodies against tooth decay and non-Hodgkin’s lymphoma from tobacco; human gastric lipase, therapeutic enzymes, dietary supplements from maize; Hepatitis B and Norwalk virus vaccines from potato; rabies vaccines from spinach; dietary supplements from Arabidopsis). The initial production platforms for plant-based pharmaceuticals were selected from conventional crops, largely because an established knowledge base already existed. Tobacco and other leafy crops such as alfalfa, lettuce and spinach are widely used as leaves can be harvested and no flowering is required. Many of these crops can be grown in contained greenhouses. Potato is also widely used and can also be grown in contained conditions. The introduction of morphological markers may aid in the recognition and traceability of crops expressing pharmaceutical products. Plant cells or plant parts may be transformed and maintained in culture to produce recombinant products in a contained environment. Plant cells in suspension or in vitro, roots, root cells and guttation fluid from leaves may be engineered to secrete proteins that may be harvested in a continuous, non-destructive manner. Most strategies in this category remain developmental and have not been commercially adopted at present. Transient expression produces GM compounds from non-GM plants via the utilisation of bacterial or viral vectors. These vectors introduce the trait into specific tissues of whole plants or plant parts, but do not insert them into the heritable genome. There are some limitations of scale and the field release of such crops will require the regulation of the vector. However, several companies have several transiently expressed products in clinical and pre-clinical trials from crops raised in physical containment.

Discrete time representation of continuous time ARMA processes

This paper derives exact discrete time representations for data generated by a continuous time autoregressive moving average (ARMA) system with mixed stock and flow data. The representations for systems comprised entirely of stocks or of flows are also given. In each case the discrete time representations are shown to be of ARMA form, the orders depending on those of the continuous time system. Three examples and applications are also provided, two of which concern the stationary ARMA(2, 1) model with stock variables (with applications to sunspot data and a short-term interest rate) and one concerning the nonstationary ARMA(2, 1) model with a flow variable (with an application to U.S. nondurable consumers’ expenditure). In all three examples the presence of an MA(1) component in the continuous time system has a dramatic impact on eradicating unaccounted-for serial correlation that is present in the discrete time version of the ARMA(2, 0) specification, even though the form of the discrete time model is ARMA(2, 1) for both models.

A novel X-ray rheometer for in situ studies of polymer melts and solutions during shear flow

A novel X-ray rheometer based on a parallel plate geometry is described. This system allows time-resolved X-ray scattering intensity data to be obtained from polymeric samples subjected to shear flow. The range of quantitative structural parameters, such as molecular orientation and inter chain correlations, which can be obtained from the data is highlighted. Examples of the utility of X-ray scattering in examining optically opaque samples and the extraction of 〈P2〉 and 〈P4〉 orientation parameters are given using anisotropic hydroxypropylcellulose solutions as the sample.

Evaluating raw ensembles with the continuous ranked probability score

The continuous ranked probability score (CRPS) is a frequently used scoring rule. In contrast with many other scoring rules, the CRPS evaluates cumulative distribution functions. An ensemble of forecasts can easily be converted into a piecewise constant cumulative distribution function with steps at the ensemble members. This renders the CRPS a convenient scoring rule for the evaluation of ‘raw’ ensembles, obviating the need for sophisticated ensemble model output statistics or dressing methods prior to evaluation. In this article, a relation between the CRPS score and the quantile score is established. The evaluation of ‘raw’ ensembles using the CRPS is discussed in this light. It is shown that latent in this evaluation is an interpretation of the ensemble as quantiles but with non-uniform levels. This needs to be taken into account if the ensemble is evaluated further, for example with rank histograms.

Turbulence dynamics near a turbulent/non-turbulent interface

The characteristics of the boundary layer separating a turbulence region from an irrotational (or non-turbulent) flow region are investigated using rapid distortion theory (RDT). The turbulence region is approximated as homogeneous and isotropic far away from the bounding turbulent/non-turbulent (T/NT) interface, which is assumed to remain approximately flat. Inviscid effects resulting from the continuity of the normal velocity and pressure at the interface, in addition to viscous effects resulting from the continuity of the tangential velocity and shear stress, are taken into account by considering a sudden insertion of the T/NT interface, in the absence of mean shear. Profiles of the velocity variances, turbulent kinetic energy (TKE), viscous dissipation rate (epsilon), turbulence length scales, and pressure statistics are derived, showing an excellent agreement with results from direct numerical simulations (DNS). Interestingly, the normalized inviscid flow statistics at the T/NT interface do not depend on the form of the assumed TKE spectrum. Outside the turbulent region, where the flow is irrotational (except inside a thin viscous boundary layer), epsilon decays as z^{-6}, where z is the distance from the T/NT interface. The mean pressure distribution is calculated using RDT, and exhibits a decrease towards the turbulence region due to the associated velocity fluctuations, consistent with the generation of a mean entrainment velocity. The vorticity variance and epsilon display large maxima at the T/NT interface due to the inviscid discontinuities of the tangential velocity variances existing there, and these maxima are quantitatively related to the thickness delta of the viscous boundary layer (VBL). For an equilibrium VBL, the RDT analysis suggests that delta ~ eta (where eta is the Kolmogorov microscale), which is consistent with the scaling law identified in a very recent DNS study for shear-free T/NT interfaces.

Estimation of the friction velocity in stably stratified boundary-layer flows over hills

A method is suggested for the calculation of the friction velocity for stable turbulent boundary-layer flow over hills. The method is tested using a continuous upstream mean velocity profile compatible with the propagation of gravity waves, and is incorporated into the linear model of Hunt, Leibovich and Richards with the modification proposed by Hunt, Richards and Brighton to include the effects of stability, and the reformulated solution of Weng for the near-surface region. Those theoretical results are compared with results from simulations using a non-hydrostatic microscale-mesoscale two-dimensional numerical model, and with field observations for different values of stability. These comparisons show a considerable improvement in the behaviour of the theoretical model when the friction velocity is calculated using the method proposed here, leading to a consistent variation of the boundary-layer structure with stability, and better agreement with observational and numerical data.