A flow system for the on-line quantitative measurement of the retention of dosage forms on biological surfaces using spectroscopy and image analysis

Measuring the retention, or residence time, of dosage forms to biological tissue is commonly a qualitative measurement, where no real values to describe the retention can be recorded. The result of this is an assessment that is dependent upon a user's interpretation of visual observation. This research paper outlines the development of a methodology to quantitatively measure, both by image analysis and by spectrophotometric techniques, the retention of material to biological tissues, using the retention of polymer solutions to ocular tissue as an example. Both methods have been shown to be repeatable, with the spectrophotometric measurement generating data reliably and quickly for further analysis.

Continuous-flow processing of gaseous ammonia using a Teflon AF-2400 tube-in-tube reactor: synthesis of thioureas and in-line titrations

A simple tube-in-tube reactor based on the gas-permeable membrane Teflon AF-2400 was used in the continuous flow reaction of gaseous ammonia with isothiocyanates and one isocyanate. A colourimetric in-line titration technique is also reported as a simple method to quantify the amount of ammonia taken up by the solvent in the system.

Spatial variability of flow statistics within regular building arrays

Turbulence statistics obtained by direct numerical simulations are analysed to investigate spatial heterogeneity within regular arrays of building-like cubical obstacles. Two different array layouts are studied, staggered and square, both at a packing density of λp=0.25 . The flow statistics analysed are mean streamwise velocity ( u− ), shear stress ( u′w′−−−− ), turbulent kinetic energy (k) and dispersive stress fraction ( u˜w˜ ). The spatial flow patterns and spatial distribution of these statistics in the two arrays are found to be very different. Local regions of high spatial variability are identified. The overall spatial variances of the statistics are shown to be generally very significant in comparison with their spatial averages within the arrays. Above the arrays the spatial variances as well as dispersive stresses decay rapidly to zero. The heterogeneity is explored further by separately considering six different flow regimes identified within the arrays, described here as: channelling region, constricted region, intersection region, building wake region, canyon region and front-recirculation region. It is found that the flow in the first three regions is relatively homogeneous, but that spatial variances in the latter three regions are large, especially in the building wake and canyon regions. The implication is that, in general, the flow immediately behind (and, to a lesser extent, in front of) a building is much more heterogeneous than elsewhere, even in the relatively dense arrays considered here. Most of the dispersive stress is concentrated in these regions. Considering the experimental difficulties of obtaining enough point measurements to form a representative spatial average, the error incurred by degrading the sampling resolution is investigated. It is found that a good estimate for both area and line averages can be obtained using a relatively small number of strategically located sampling points.

The effect of flow field & geometry on the dynamic contact angle

A number of recent experiments suggest that, at a given wetting speed, the dynamic contact angle formed by an advancing liquid-gas interface with a solid substrate depends on the flow field and geometry near the moving contact line. In the present work, this effect is investigated in the framework of an earlier developed theory that was based on the fact that dynamic wetting is, by its very name, a process of formation of a new liquid-solid interface (newly “wetted” solid surface) and hence should be considered not as a singular problem but as a particular case from a general class of flows with forming or/and disappearing interfaces. The results demonstrate that, in the flow configuration of curtain coating, where a liquid sheet (“curtain”) impinges onto a moving solid substrate, the actual dynamic contact angle indeed depends not only on the wetting speed and material constants of the contacting media, as in the so-called slip models, but also on the inlet velocity of the curtain, its height, and the angle between the falling curtain and the solid surface. In other words, for the same wetting speed the dynamic contact angle can be varied by manipulating the flow field and geometry near the moving contact line. The obtained results have important experimental implications: given that the dynamic contact angle is determined by the values of the surface tensions at the contact line and hence depends on the distributions of the surface parameters along the interfaces, which can be influenced by the flow field, one can use the overall flow conditions and the contact angle as a macroscopic multiparametric signal-response pair that probes the dynamics of the liquid-solid interface. This approach would allow one to investigate experimentally such properties of the interface as, for example, its equation of state and the rheological properties involved in the interface’s response to an external torque, and would help to measure its parameters, such as the coefficient of sliding friction, the surface-tension relaxation time, and so on.

Catchment-scale modelling of flow and nutrient transport in the Chalk unsaturated zone

The unsaturated zone exerts a major control on the delivery of nutrients to Chalk streams, yet flow and transport processes in this complex, dual-porosity medium have remained controversial. A major challenge arises in characterising these processes, both at the detailed mechanistic level and at an appropriate level for inclusion within catchment-scale models for nutrient management. The lowland catchment research (LOCAR) programme in the UK has provided a unique set of comprehensively instrumented groundwater-dominated catchments. Of these, the Pang and Lambourn, tributaries of the Thames near Reading, have been a particular focus for research into subsurface processes and surface water-groundwater interactions. Data from LOCAR and other sources, along with a new dual permeability numerical model of the Chalk, have been used to explore the relative roles of matrix and fracture flow within the unsaturated zone and resolve conflicting hypotheses of response. From the improved understanding gained through these explorations, a parsimonious conceptualisation of the general response of flow and transport within the Chalk unsaturated zone was formulated. This paper summarises the modelling and data findings of these explorations, and describes the integration of the new simplified unsaturated zone representation with a catchment-scale model of nutrients (INCA), resulting in a new model for catchment-scale flow and transport within Chalk systems: INCA-Chalk. This model is applied to the Lambourn, and results, including hindcast and forecast simulations, are presented. These clearly illustrate the decadal time-scales that need to be considered in the context of nutrient management and the EU Water Framework Directive. (C) 2007 Elsevier B.V. All rights reserved.

The acoustic signature of fluid flow in complex porous media

Effective medium approximations for the frequency-dependent and complex-valued effective stiffness tensors of cracked/ porous rocks with multiple solid constituents are developed on the basis of the T-matrix approach (based on integral equation methods for quasi-static composites), the elastic - viscoelastic correspondence principle, and a unified treatment of the local and global flow mechanisms, which is consistent with the principle of fluid mass conservation. The main advantage of using the T-matrix approach, rather than the first-order approach of Eshelby or the second-order approach of Hudson, is that it produces physically plausible results even when the volume concentrations of inclusions or cavities are no longer small. The new formulae, which operates with an arbitrary homogeneous (anisotropic) reference medium and contains terms of all order in the volume concentrations of solid particles and communicating cavities, take explicitly account of inclusion shape and spatial distribution independently. We show analytically that an expansion of the T-matrix formulae to first order in the volume concentration of cavities (in agreement with the dilute estimate of Eshelby) has the correct dependence on the properties of the saturating fluid, in the sense that it is consistent with the Brown-Korringa relation, when the frequency is sufficiently low. We present numerical results for the (anisotropic) effective viscoelastic properties of a cracked permeable medium with finite storage porosity, indicating that the complete T-matrix formulae (including the higher-order terms) are generally consistent with the Brown-Korringa relation, at least if we assume the spatial distribution of cavities to be the same for all cavity pairs. We have found an efficient way to treat statistical correlations in the shapes and orientations of the communicating cavities, and also obtained a reasonable match between theoretical predictions (based on a dual porosity model for quartz-clay mixtures, involving relatively flat clay-related pores and more rounded quartz-related pores) and laboratory results for the ultrasonic velocity and attenuation spectra of a suite of typical reservoir rocks. (C) 2003 Elsevier B.V. All rights reserved.

Dual-specificity phosphatases in the hypo-osmotic stress response of keratin-defective epithelial cell lines

Although mutations in intermediate filament proteins cause many human disorders, the detailed pathogenic mechanisms and the way these mutations affect cell metabolism are unclear. In this study, selected keratin mutations were analysed for their effect on the epidermal stress response. Expression profiles of two keratin-mutant cell lines from epidermolysis bullosa simplex patients (one severe and one mild) were compared to a control keratinocyte line before and after challenge with hypo-osmotic shock, a common physiological stress that transiently distorts cell shape. Fewer changes in gene expression were found in cells with the severely disruptive mutation (55 genes altered) than with the mild mutation (174 genes) or the wild type cells (261 genes) possibly due to stress response pre-activation in these cells. We identified 16 immediate-early genes contributing to a general cell response to hypo-osmotic shock, and 20 genes with an altered expression pattern in the mutant keratin lines only. A number of dual-specificity phosphatases (MKP-1, MKP-2, MKP-3, MKP-5 and hVH3) are differentially regulated in these cells, and their downstream targets p-ERK and p-p38 are significantly up-regulated in the mutant keratin lines. Our findings strengthen the case for the expression of mutant keratin proteins inducing physiological stress, and this intrinsic stress may affect the cell responses to secondary stresses in patients' skin.

A dual role for integrin-linked kinase in platelets: regulating integrin function and alpha-granule secretion

Integrin-linked kinase (ILK) has been implicated in the regulation of a range of fundamental biological processes such as cell survival, growth, differentiation, and adhesion. In platelets ILK associates with beta 1- and beta 3-containing integrins, which are of paramount importance for the function of platelets. Upon stimulation of platelets this association with the integrins is increased and ILK kinase activity is up-regulated, suggesting that ILK may be important for the coordination of platelet responses. In this study a conditional knockout mouse model was developed to examine the role of ILK in platelets. The ILK-deficient mice showed an increased bleeding time and volume, and despite normal ultrastructure the function of ILK-deficient platelets was decreased significantly. This included reduced aggregation, fibrinogen binding, and thrombus formation under arterial flow conditions. Furthermore, although early collagen stimulated signaling such as PLC gamma 2 phosphorylation and calcium mobilization were unaffected in ILK-deficient platelets, a selective defect in alpha-granule, but not dense-granule, secretion was observed. These results indicate that as well as involvement in the control of integrin affinity, ILK is required for alpha-granule secretion and therefore may play a central role in the regulation of platelet function. (Blood. 2008; 112: 4523-4531)

Comparative study of the performance of the M-cycle counter-flow and cross-flow heat exchangers for indirect evaporative cooling - paving the path towards sustainable cooling of buildings

This paper provides a comparative study of the performance of cross-flow and counter-flow M-cycle heat exchangers for dew point cooling. It is recognised that evaporative cooling systems offer a low energy alternative to conventional air conditioning units. Recently emerged dew point cooling, as the renovated evaporative cooling configuration, is claimed to have much higher cooling output over the conventional evaporative modes owing to use of the M-cycle heat exchangers. Cross-flow and counter-flow heat exchangers, as the available structures for M-cycle dew point cooling processing, were theoretically and experimentally investigated to identify the difference in cooling effectiveness of both under the parallel structural/operational conditions, optimise the geometrical sizes of the exchangers and suggest their favourite operational conditions. Through development of a dedicated computer model and case-by-case experimental testing and validation, a parametric study of the cooling performance of the counter-flow and cross-flow heat exchangers was carried out. The results showed the counter-flow exchanger offered greater (around 20% higher) cooling capacity, as well as greater (15%–23% higher) dew-point and wet-bulb effectiveness when equal in physical size and under the same operating conditions. The cross-flow system, however, had a greater (10% higher) Energy Efficiency (COP). As the increased cooling effectiveness will lead to reduced air volume flow rate, smaller system size and lower cost, whilst the size and cost are the inherent barriers for use of dew point cooling as the alternation of the conventional cooling systems, the counter-flow system is considered to offer practical advantages over the cross-flow system that would aid the uptake of this low energy cooling alternative. In line with increased global demand for energy in cooling of building, largely by economic booming of emerging developing nations and recognised global warming, the research results will be of significant importance in terms of promoting deployment of the low energy dew point cooling system, helping reduction of energy use in cooling of buildings and cut of the associated carbon emission.

Location and characteristics of the reconnection X line deduced from low-altitude satellite and ground-based observations: 2. Defense Meteorological Satellite Program and European Incoherent Scatter data

We present an analysis of a cusp ion step, observed by the Defense Meteorological Satellite Program (DMSP) F10 spacecraft, between two poleward moving events of enhanced ionospheric electron temperature, observed by the European Incoherent Scatter (EISCAT) radar. From the ions detected by the satellite, the variation of the reconnection rate is computed for assumed distances along the open-closed field line separatrix from the satellite to the X line, do. Comparison with the onset times of the associated ionospheric events allows this distance to be estimated, but with an uncertainty due to the determination of the low-energy cutoff of the ion velocity distribution function, ƒ(ν). Nevertheless, the reconnection site is shown to be on the dayside magnetopause, consistent with the reconnection model of the cusp during southward interplanetary magnetic field (IMF). Analysis of the time series of distribution function at constant energies, ƒ(ts), shows that the best estimate of the distance do is 14.5±2 RE. This is consistent with various magnetopause observations of the signatures of reconnection for southward IMF. The ion precipitation is used to reconstruct the field-parallel part of the Cowley D ion distribution function injected into the open low-latitude boundary layer in the vicinity of the X line. From this reconstruction, the field-aligned component of the magnetosheath flow is found to be only −55±65 km s−1 near the X line, which means either that the reconnection X line is near the stagnation region at the nose of the magnetosphere, or that it is closely aligned with the magnetosheath flow streamline which is orthogonal to the magnetosheath field, or both. In addition, the sheath Alfvén speed at the X line is found to be 220±45 km s−1, and the speed with which newly opened field lines are ejected from the X line is 165±30 km s−1. We show that the inferred magnetic field, plasma density, and temperature of the sheath near the X line are consistent with a near-subsolar reconnection site and confirm that the magnetosheath field makes a large angle (>58°) with the X line.

Location and characteristics of the reconnection X line deduced from low-altitude satellite and ground-based observations: 1. Theory

A method for estimating both the Alfvén speed and the field-aligned flow of the magnetosheath at the magnetopause reconnection site is presented. The method employs low-altitude cusp ion observations and requires the identification of a feature in the cusp ion spectra near the low-energy cutoff which will often be present for a low-latitude dayside reconnection site. The appearance of these features in data of limited temporal, energy, and pitch angle resolution is illustrated by using model calculations of cusp ion distribution functions. These are based on the theory of ion acceleration at the dayside magnetopause and allow for the effects on the spectrum of flight times of ions precipitating down newly opened field lines. In addition, the variation of the reconnection rate can be evaluated, and comparison with ground-based observations of the corresponding sequence of transient events allows the field-aligned distance from the ionosphere to the reconnection site to be estimated.

Flow-aligned jets in the magnetospheric cusp: Results from the Geospace Environment Modeling Pilot Program

The extended flight of the Airborne Ionospheric Observatory during the Geospace Environment Modeling (GEM) Pilot program on January 16, 1990, allowed continuous all-sky monitoring of the two-dimensional ionospheric footprint of the northward interplanetary magnetic field (IMF) cusp in several wavelengths. Especially important in determining the locus of magnetosheath electron precipitation was the 630.0-nm red line emission. The most striking morphological change in the images was the transient appearance of zonally elongated regions of enhanced 630.0-nm emission which resembled “rays” emanating from the centroid of the precipitation. The appearance of these rays was strongly correlated with the Y component of the IMF: when the magnitude of By was large compared to Bz, the rays appeared; otherwise, the distribution was relatively unstructured. Late in the flight the field of view of the imager included the field of view of flow measurements from the European incoherent scatter radar (EISCAT). The rays visible in 630.0-nm emission exactly aligned with the position of strong flow jets observed by EISCAT. We attribute this correspondence to the requirement of quasi-neutrality; namely, the soft electrons have their largest precipitating fluxes where the bulk of the ions precipitate. The ions, in regions of strong convective flow, are spread out farther along the flow path than in regions of weaker flow. The occurrence and direction of these flow bursts are controlled by the IMF in a manner consistent with newly opened flux tubes; i.e., when |By| > |Bz|, tension in the reconnected field lines produce east-west flow regions downstream of the ionospheric projection of the x line. We interpret the optical rays (flow bursts), which typically last between 5 and 15 min, as evidence of periods of enhanced dayside (or lobe) reconnection when |By| > |Bz|. The length of the reconnection pulse is difficult to determine, however, since strong zonal flows would be expected to persist until the tension force in the field line has decayed, even if the duration of the enhanced reconnection was relatively short.

Causes of plasma flow bursts and dayside auroral transients: An evaluation of two models Invoking reconnection pulses and changes in the Y component of the magnetosheath field

Longitudinal flow bursts observed by the European Incoherent Scatter (EISCAT) radar, in association with dayside auroral transients observed from Svalbard, have been interpreted as resulting from pulses of enhanced reconnection at the dayside magnetopause. However, an alternative model has recently been proposed for a steady rate of magnetopause reconnection, in which the bursts of longitudinal flow are due to increases in the field line curvature force, associated with the By component of the magnetosheath field. We here evaluate these two models, using observations on January 20, 1990, by EISCAT and a 630-nm all-sky camera at Ny Ålesund. For both models, we predict the behavior of both the dayside flows and the 630-nm emissions on newly opened field lines. It is shown that the signatures of steady reconnection and magnetosheath By changes could possibly resemble the observed 630-nm auroral events, but only for certain locations of the observing site, relative to the ionospheric projection of the reconnection X line: however, in such cases, the flow bursts would be seen between the 630-nm transients and not within them. On the other hand, the model of reconnection rate pulses predicts that the flows will be enhanced within each 630-nm transient auroral event. The observations on January 20, 1990, are shown to be consistent with the model of enhanced reconnection rate pulses over a background level and inconsistent with the effects of periodic enhancements of the magnitude of the magnetosheath By component. We estimate that the reconnection rate within the pulses would have to be at least an order of magnitude larger than the background level between the pulses.

The characteristics of the magnetopause reconnection X-line deduced from low-altitude satellite observations of cusp ions

We present an analysis of a “quasi-steady” cusp ion dispersion signature observed at low altitudes. We reconstruct the field-parallel part of the Cowley-D ion distribution function, injected into the open LLBL in the vicinity of the reconnection X-line. From this we find the field-parallel magnetosheath flow at the X-line was only 20 ± 60 km s−1, placing the reconnection site close to the flow streamline which is perpendicular to the magnetosheath field. Using interplanetary data and assuming the subsolar magnetopause is in pressure balance, we derive a wealth of information about the X-line, including: the density, flow, magnetic field and Alfvén speed of the magnetosheath; the magnetic shear across the X-line; the de-Hoffman Teller speed with which field lines emerge from the X-line; the magnetospheric field; and the ion transmission factor across the magnetopause. The results indicate that some heating takes place near the X-line as the ions cross the magnetopause, and that sheath densities may be reduced in a plasma depletion layer. We also compute the reconnection rate. Despite its quasi-steady appearance on an ion spectrogram, this cusp is found to reveal a large pulse of enhanced reconnection rate.

Auroral and plasma flow transients at magnetic noon

We present observations of a transient event in the dayside auroral ionosphere at magnetic noon. F-region plasma convection measurements were made by the EISCAT radar, operating in the beamswinging “Polar” experiment mode, and simultaneous observations of the dayside auroral emissions were made by optical meridian-scanning photometers and all-sky TV cameras at Ny Ålesund, Spitzbergen. The data were recorded on 9 January 1989, and a sequence of bursts of flow, with associated transient aurora, were observed between 08:45 and 11:00 U.T. In this paper we concentrate on an event around 09:05 U.T. because that is very close to local magnetic noon. The optical data show a transient intensification and widening (in latitude) of the cusp/cleft region, as seen in red line auroral emissions. Over an interval of about 10 min, the band of 630 nm aurora widened from about 1.5° of invariant latitude to over 5° and returned to its original width. Embedded within the widening band of 630 nm emissions were two intense, active 557.7 nm arc fragments with rays which persisted for about 2 min each. The flow data before and after the optical transient show eastward flows, with speeds increasing markedly with latitude across the band of 630 nm aurora. Strong, apparently westward, flows appeared inside the band while it was widening, but these rotated round to eastward, through northward, as the band shrunk to its original width. The observed ion temperatures verify that the flow speeds during the transient were, to a large extent, as derived using the beamswinging technique; but they also show that the flow increase initially occurred in the western azimuth only. This spatial gradient in the flow introduces ambiguity in the direction of these initial flows and they could have been north-eastward rather than westward. However, the westward direction derived by the beamswinging is consistent with the motion of the colocated and coincident active 557.7 nm arc fragment, A more stable transient 557.7 nm aurora was found close to the shear between the inferred westward flows and the persisting eastward flows to the North. Throughout the transient, northward flow was observed across the equatorward boundary of the 630 nm aurora. Interpretation of the data is made difficult by lack of IMF data, problems in distinguishing the cusp and cleft aurora and uncertainty over which field lines are open and which are closed. However, at magnetic noon there is a 50% probability that we were observing the cusp, in which case from its southerly location we infer that the IMF was southward and many features are suggestive of time-varying reconnection at a single X-line on the dayside magnetopause. This IMF orientation is also consistent with the polar rain precipitation observed simultaneously by the DMSP-F9 satellite in the southern polar cap. There is also a 25% chance that we were observing the cleft (or the mantle poleward of the cleft). In this case we infer that the IMF was northward and the transient is well explained by reconnection which is not only transient in time but occurs at various sites located randomly on the dayside magnetopause (i.e. patchy in space). Lastly, there is a 25% chance that we were observing the cusp poleward of the cleft, in which case we infer that IMF Bz was near zero and the transient is explained by a mixture of the previous two interpretations.