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PubMed2004

Modelling hydroenvironmental and health risk assessment parameters along the South Wales Coast.

This paper highlights the increasing concerns relating to hydroenvironmetal issues and cites recent examples of the challenges now being regularly faced by hydroenvironmetal scientists and engineers. The limitations and restrictions of both physical (or laboratory) and numerical (or computer based) hydraulic models used in the planning and management of aquatic basins are discussed. General details are given of numerical models used for flow and water quality concentration predictions in estuarine waters, with particular application to the challenges occurring along the South Wales coast. A highly accurate and non-diffusive finite difference scheme that solves the transport equation for predicting water quality indicators and suspended sediment concentration distributions is also discussed. In particular, details are outlined of the extension of the water quality indicators of faecal coliforms, as required to comply with the EU Bathing Water Directive, to predict health risk assessment, in the form of predicting the risk of gastroenteritis. Three example research projects along the South Wales coast are described; the projects involve the application of two-dimensional and three-dimensional hydroenvironmetal models to predict flow patterns and water quality indicator organism distributions in the coastal receiving waters. These studies include: (i) a curvilinear finite difference approach to modelling flows in the Bristol Channel, (ii) coastal health risk predictions in Swansea Bay using combined water quality and epidemiological models, and (iii) combined sewer overflow discharges into Cardiff Bay.

Computer Simulation↗
PubMed1999

Effect of blood perfusion on diffusive transport in peritoneal dialysis.

BACKGROUND: Diffusive transport between blood and dialysate during peritoneal dialysis is evaluated in clinical and experimental studies by the diffusive mass transport coefficient, KBD. This global parameter depends on the local diffusive characteristics of the blood capillary wall (permeability) and the tissue, as well as on the density and distribution of capillaries within the tissue. It also depends on the rate of delivery (or washout) of solutes from the tissue with blood flow, that is, on the rate of tissue perfusion. However, the role of blood perfusion in peritoneal transport has not been theoretically evaluated. METHODS: The relationship between the local characteristics of the peritoneal tissue and the global diffusive mass transport coefficient was studied using a new extended version of the distributed model for peritoneal transport, which included the effect of tissue perfusion and capillary surface area on the blood-tissue transport. RESULTS: The solute concentration profiles within the tissue were found to depend on the solute penetration depth, which is equal to the square root of the ratio of the solute diffusivity in tissue to the solute clearance from the capillary bed to tissue. It was shown that KBD might be interpreted as the dialysance of a capillary bed of a characteristic size that would be immersed directly in dialysate. A definition of the effective peritoneal blood flow (EPBF; the blood flow within the tissue layer) was formulated, and it was shown that EPBF depends on the local transport characteristics for the solute. Assuming typical values of the model parameters (known from physiological studies), the values of KBD and EPBF for urea, creatinine, glucose, and CO2 were calculated and compared with the measured values with good qualitative agreement. The transient initial increase of KBD values observed at the beginning of the peritoneal dialysis dwell was interpreted as a transient sixfold increase in tissue perfusion and a twofold increase in the capillary surface area. CONCLUSION: The distributed model can be useful as a theoretical tool for detailed physiological interpretations of changes in peritoneal transport associated with changes in peritoneal microcirculation and structure of the interstitium.

Ascitic Fluid↗
PubMed1984

A transmembrane electrical potential generated by respiration is not equivalent to a diffusion potential of the same magnitude for ATP synthesis by Bacillus firmus RAB.

ATP synthesis by starved whole cells of alkalophilic Bacillus firmus RAB was energized by addition of DL-malate or by imposition of a valinomycin-mediated K+ diffusion potential. At pH 9.0, the transmembrane electrical potentials produced by these two means were similar in magnitude, at close to -170 mV. While N,N'-dicyclohexylcarbodiimide-sensitive ATP synthesis occurred upon the addition of DL-malate, no ATP was synthesized in response to a diffusion potential. In contrast, Na+-dependent accumulation of alpha-aminoisobutyric acid was energized equally well by DL-malate or a diffusion potential at pH 9.0. Even at pH 7.0, DL-malate was more efficacious than a diffusion potential in energizing ATP synthesis as assessed by determining the phosphorylation potentials generated at transmembrane electrical potential values of different magnitudes. Both modes of energization did, however, result in N,N'-dicyclohexylcarbodiimide-sensitive ATP synthesis at pH 7.0. The results of these studies are consistent with a model of energy coupling in which one pathway of protons between the respiratory proton pumps and the H+-translocating ATPase is direct or localized. Whereas an artificially imposed electrochemical gradient of protons can energize ATP synthesis under certain experimental conditions, in the proton-poor milieu that is optimal for growth of alkalophilic bacilli, the direct proton pathway may be crucial.

Adenosine Triphosphate↗
PubMed2005

Quantitative magnetization transfer by trains of radio frequency pulses in human brain: extension of a free evolution model to continuous-wave-like conditions.

A theoretical model of free evolution between repeated magnetic transfer (MT) pulses was extended to continuous-wave (CW)-like conditions showing that only the repetitive "direct" saturation of bulk water changes the transient and stationary behavior. The influence of the pulse repetition period (PR) on progressive saturation was studied in cortical gray matter (GM) and central white matter (WM) under conditions of short periods of free evolution and strong macromolecular saturation. Interpulse delays of 3 ms were achieved in vivo on a 1.5-T MR system with bell-shaped MT pulses of 12-ms duration and nominal flip angles of up to 1440 degrees and single-shot readout by a stimulated echo acquisition mode localization sequence. The frequency offset was chosen between 1 and 3 kHz to avoid excessive direct saturation. The stationary MT ratio (MTR) followed an inverse linear PR dependence, showing a consistent partial saturation of about 90% at zero PR for both WM and GM. Comparison to a relaxation-matched liquid indicated the presence of MT, but not necessarily of direct saturation. The transient behavior indicated considerable direct saturation, but this could also be explained by MT. These inconsistencies showed that the intervals of time evolution in our experiments were too long to be modeled by CW-like conditions. Free evolution takes place during the whole PR rather than during the interpulse delay only. Quantification using the rates of free evolution theory yielded the saturations and rate constants necessary to explain the observed behavior. The theory of rapid CW-like pulsing provides an upper limit for the rate of progressive saturation. This limit is approached at PR below an estimated value of 5 ms. The phenomenological PR dependence of the steady-state MTR may indicate that MT exceeded the direct saturation. Unlike to an idealized CW experiment, the extrapolated value at zero PR is subject to direct effects and not a physically meaningful constant.

Adult↗
PubMed2006

Intralymphatic dendritic cell vaccination induces tumor antigen-specific, skin-homing T lymphocytes.

PURPOSE: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen-specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. EXPERIMENTAL DESIGN: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. RESULTS: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen-specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. CONCLUSIONS: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are "imprinted" in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.

Adult↗
PubMed1989

Experimental models of brain injury.

General categories of experimental brain injury models are reviewed regarding their clinical significance, and two new models are presented that use different methodology to produce injury. This report describes and characterizes the pathophysiologic changes produced by a novel fluid percussion (FP) method and a controlled cortical impact (CI) technique, both developed at the General Motors Research Laboratories (GMRL). The new models are compared to prior experimental brain injury techniques in relation to ongoing physical and analytical modeling used in automotive safety research by GMRL. Experimental results from our laboratory indicate that although the FP technique, currently the most widely used method for producing brain injury, is useful for producing graded injury responses systemically and centrally, it is not well-suited for detailed biomechanical analyses. This conclusion is based on high-speed cineradiographic studies where the physiologic saline in the FP cannula was substituted with a radiopaque contrast medium (Conray 1:1 dilution/saline). High speed x-ray movies (1000 fps) were taken of the fluid percussion pulse (1.5-3.4 atm/20 msec) in sagittal, dorsal, and frontal planes of orientation. When viewed together, the cineradiography revealed a complex, dynamic interaction between the injected fluid and the skull/cranial contents. Rapid lateral and anterior/posterior epidural fluid flow suggest that the pathology and dysfunction following FP brain injury reflects diffuse mechanical loading of the brain. Because fluid is used to transfer mechanical energy to brain tissue, and because fluid flow characteristics (i.e., direction, velocity, and displacement) are dependent on the brain geometry and species used, accurate analytical and biomechanical analyses of the resultant injury would be difficult at best. In contrast, the cortical impact model of experimental brain injury uses a known impact interface and a measurable, controllable impact velocity and cortical compression. These controlled variables enable the amount of deformation and the change in deformation over time to be accurately determined. In addition, the CI model produces graded, reproducible cortical contusion, prolonged functional coma, and extensive axonal injury, unlike the FP technique. The quantifiable nature of the single mechanical input used to produce the injury allows correlations to be made between the amount of deformation and the resultant pathology and functional changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Multi-scale models of local control of calcium induced calcium release.

Calcium-induced-calcium-release in cardiac myocytes is the release of Ca(2+) from the sarcoplasmic reticulum (SR) triggered by Ca(2+) entering the cell through L-type Ca(2+) channels. The Ca(2+) is released through ryanodine receptors which 'sense' local [Ca(2+)] in the small region (the diadic space) positioned between the t-tubules and the SR. The length-scale of a single diad is of the order of 10nm and the diffusion time-scale is of order of 1 micros with each cell containing approximately 10,000 diadic spaces which act independently. However, typically one is interested in Ca(2+) currents at the whole cell level and higher. This is a multi-scale problem and cannot be solved by direct computation. In this paper we develop a general framework for deriving approximate solutions of these models.

Animals↗
PubMed2001

Attenuation of neointima formation following arterial injury in PAI-1 deficient mice.

Atherosclerosis is a chronic inflammatory disease in which the fibrinolytic system has been implicated as playing a major role. In order to directly assess the physiological impact an imbalanced fibrinolytic system has on both early and late stages of this disease, mice deficient for PAI-1 (PAI-1-/-) were used in a model of vascular injury/repair and compared to wildtype mice (WT). Copper-containing cuffs were placed around the carotid arteries of these mice and the injured arteries were removed at either 7 or 21 days for histological analyses. At both times after injury, fibrin was prevalent in WT arteries, whereas only diffuse in PAI-1-/- arteries. At 21 days after injury, a prominent, multilayered neointima was evident in WT arteries, with no evidence of a neointima in PAI-1-/- arteries. Results from this study directly confirm the involvement of the fibrinolytic system in vascular repair processes following injury and indicate that fibrin could potentially play a role in lesion formation by stimulating smooth muscle cell proliferation, collagen synthesis, and intracellular cholesterol accumulation.

Animals↗
PubMed2005

Model for Brownian motion in soft-jammed systems.

Brownian motion in soft-jammed systems (pastes) is directly described by taking into account the specific mechanical characteristics of the material surrounding the moving object. In particular we obtain explicit forms for the fluctuation-dissipation equation and the specific characteristics of diffusion through a soft-jammed system.

Journal Article↗
PubMed2002

Kinetics and equilibrium in the immunoradiometric assay (IRMA) of thyroglobuline.

This paper studies the kinetics of the thyroglobuline reaction with its specific antibody immobilised on the inner wall of the reaction tube, and the subsequent binding of the immunocomplex formed with a second 125I-labelled antibody. These reactions are used in the immunoradiometric determination of thyroglobuline. Independent variables were analyte and labelled antibody, temperature, viscosity, and the medium's ionic strength. For the global process, mono-exponential kinetics were found to be dependent on the concentrations, such dependence fitting with the models discussed in the paper. Viscosity results clearly indicate its negative influence on the direct reaction rate. Ionic strength shows noticeable, but not too relevant, effects, which suggests that the variation caused by the glycerol addition is not due to the influence of the dielectric constant of the solutions used. The effect of temperature shows activation parameters similar to the viscous flow energy of water, which suggests diffusion control for the global process.

Diffusion↗
PubMed2001

Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA.

Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA) are autosomal dominant, neurodegenerative disorders caused by the expansion of polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We have previously generated mouse models of these disorders, using transgenes expressed via the prion protein promoter. Here, we report the first direct comparison of abnormalities in these models. The HD mice show abbreviated lifespans (4-6 months), hypoactivity, and mild impairment of motor skills. The DRPLA mice show severe tremors, are hyperactive, and are profoundly uncoordinated. Neuropathological analyses reveal that the distribution of diffuse nuclear immunolabeling and neuronal intranuclear inclusions (NII's), in the CNS of both models, was remarkably similar. Cytoplasmic aggregates of huntingtin were the major distinguishing neuropathological feature of the HD mice; mutant atrophin-1 accumulated/aggregated only in the nucleus. We suggest that the distinct behavioral and neuropathological phenotypes in these mice reflect differences in the way these mutant proteins perturb neuronal function.

Aggression↗
PubMed1981

Model film studies in enzyme histochemistry with special reference to glucose-6-phosphate dehydrogenase.

This paper deals with the progress made over the last few years in our understanding of enzyme cytochemical staining methods as studied using a fundamental approach with the aid of a model system of thin gel films. Although model films with a matrix of polyacrylamide have been mostly used, the properties and possible applications of other matrices are also reviewed. The chemical aspects of the entrapment of enzyme molecules into a matrix are summarized. Special attention has been paid in model film studies to the principles of the trapping reaction of a diffusable precursor resulting from the enzymatic conversion of a substrate. They are considered here as they concern the cytochemical demonstration of acid phosphatase activity with a lead salt. The effect of fixatives on different enzyme activities, the diffusion rate of substrates and chromogenic compounds to the enzyme site, and enzyme kinetics under cytochemical conditions are also discussed, since they are factors which influence the final results of the staining procedures. The advantage of model film studies in enabling the direct correlation of cytochemical and biochemical results is outlined with special reference to the cytochemical determination of glucose-6-phosphate dehydrogenase with Tetra Nitro BT. A method for determining enzyme activities in the soluble fraction of isolated cells after incorporation in model films is described for the first time. This method has proved to be highly appropriate for microscopical observations of glucose-6-phosphate dehydrogenase activity in single cells, because it results in a good morphology and no formazan precipitates outside the cells. On the other hand, this type of model film forms a bridge between fundamental model film studies using purified enzyme and quantitative enzyme cytochemistry performed in situ.

Acid Phosphatase↗
PubMed1997

[Transmyocardial laser revascularization in stable and unstable angina pectoris].

Endstage coronary artery disease still remains a therapeutic challenge. An increasing number of patients is no longer amenable for direct revascularization by PTCA or coronary bypass surgery and does also no longer respond to maximum medical therapy. This fact has directed the interest again towards surgical techniques of indirect revascularization, which had been introduced by Beck and other surgeons more than 60 years ago. Among these attempts we can also find transmyocardial needle punctures, firstly performed by Sen in Bombay. In the early eighties it was Mirhoseini, who used a laser for creating these transmural channels, primarily in combination with coronary bypass surgery at the arrested heart and later on together with Crew as a sole therapy at the beating heart. The idea behind this transmyocardial laser revascularization (TMLR) was a "reptilization" of the human heart, which meant a direct blood supply from the ventricle into the ischemic myocardium. Whereas this theory has not proven to be true, as the surface area of these channels is not sufficient for the nutrition of the surrounding myocardial tissue by diffusion or convection, different models have been developed by anatomical, experimental and clinical studies, such as the connection between the laser channels and intramyocardial vessels or capillaries, analogous to ventriculo-coronary connections in human anatomy or pathology as for example those connections described in children with pulmonary atresia and intact ventricular septum or the Thebesian veins. Moreover the laser trauma may also simply contribute to the induction of neoangiogenesis. While the function of TMLR is still not clearly defined, clinical studies in the United States and also in other countries have proven the clinical efficacy in a cohort of severely diseased patients undergoing this procedure. Accordingly more than 2/3 of all patients after TMLR showed a significant improvement of more than 2 angina classes (CCS) as well as a decrease in medication and hospitalization. Moreover there was also a reduction of ischemic areas demonstrated by szintigraphy and, in one study from Houston, also by positron emission tomography. While the overall mortality in all those studies is still considerably high, a reduction could be achieved by a stricter selection of patients excluding especially those with a severely impaired left ventricular function. As demonstrated by preliminary data from the last phase III FDA-study, TMLR may even reduce long-term mortality compared to maximum medical therapy in a randomized group of patients. Our own experiences in 134 patients also confirmed a significant reduction of angina after TMLR alone (n = 67) or in combination with bypass surgery (n = 67) with the majority of patients being in angina class 1 and 2 (CCS) 6 months after surgery. All of these patients were in angina class 3 and 4 before surgery. Nuclear scans could demonstrate an improved perfusion in more than 40%. Further studies as well as other clinical and also experimental investigations have still to be awaited, before the definitive role of TMLR within the armamentarium against coronary artery disease can be determined. However, it is already a therapeutic option for those highly symptomatic patients, who cannot be offered a different treatment modality.

Adult↗
PubMed2005

Stochastic analysis to assess the spatial distribution of groundwater nitrate concentrations in the Po catchment (Italy).

A large database including temporal trends of physical, ecological and socio-economic data was developed within the EUROCAT project. The aim was to estimate the nutrient fluxes for different socio-economic scenarios at catchment and coastal zone level of the Po catchment (Northern Italy) with reference to the Water Quality Objectives reported in the Water Framework Directive (WFD 2000/60/CE) and also in Italian legislation. Emission data derived from different sources at national, regional and local levels are referred to point and non-point sources. While non-point (diffuse) sources are simply integrated into the nutrient flux model, point sources are irregularly distributed. Intensive farming activity in the Po valley is one of the main Pressure factors Driving groundwater pollution in the catchment, therefore understanding the spatial variability of groundwater nitrate concentrations is a critical issue to be considered in developing a Water Quality Management Plan. In order to use the scattered point source data as input in our biogeochemical and transport models, it was necessary to predict their values and associated uncertainty at unsampled locations. This study reports the spatial distribution and uncertainty of groundwater nitrate concentration at a test site of the Po watershed using a probabilistic approach. Our approach was based on geostatistical sequential Gaussian simulation used to yield a series of stochastic images characterized by equally probable spatial distributions of the nitrate concentration across the area. Post-processing of many simulations allowed the mapping of contaminated and uncontaminated areas and provided a model for the uncertainty in the spatial distribution of nitrate concentrations.

Agriculture↗
PubMed2006

A kinetic study of the intercalation of lithium salts into Al(OH)3.

The intercalation of five lithium salts into the gibbsite and bayerite polymorphs of Al(OH)3 has been studied using in situ energy-dispersive X-ray diffraction. The kinetics and mechanisms of the reactions have been modeled using the Avrami-Erofe'ev model. The kinetic data suggest that the reaction mechanisms are predominantly nucleation controlled, although the intercalation of LiNO3 into bayerite and of Li2SO4 into gibbsite proceed via two-stage mechanisms, one part of which is diffusion controlled. All the reactions proceed directly from the host to the product, except for the intercalation of Li2SO4 into gibbsite where a more hydrated intermediate form of [LiAl2(OH)6]2SO4 x yH2O is generated prior to the final product.

Journal Article↗
PubMed2000

Quantitative TEM of point defects in Si

We review the use of transmission electron microscopy (TEM) to provide a quantitative measurement of both vacancy and interstitial clusters in ion-implanted silicon. Interstitials agglomerate into rod-like defects on 131I) planes, and the evaporation of these defects can be directly correlated to the diffusion enhancements observed during annealing of ion-damaged silicon. Vacancy clusters are easily detected in TEM once they have been labelled using a Au-diffusion technique. The combination of the two approaches provides a quantitative test for models of implantation and annealing in silicon. Detailed models for point defect behaviour, which include Ostwald-ripening and the surface recombination velocity, reproduce all of the crucial features of the observed defect annealing.

Journal Article↗
PubMed2002

Parameters and equilibrium profiles for large-area surface-wave sustained plasmas.

The equilibrium profiles of the plasma parameters of large-area rf discharges in a finite-length metal-shielded dielectric cylinder are computed using a two-dimensional fluid code. The rf power is coupled to the plasma through edge-localized surface waves traveling in the azimuthal direction along the plasma edge. It is shown that self-consistent accounting for axial plasma diffusion and radial nonuniformity of the electron temperature can explain the frequently reported deviations of experimentally measured radial density profiles from that of the conventional linear diffusion models. The simulation results are in a good agreement with existing experimental data obtained from surface-wave sustained large-diameter plasmas.

Journal Article↗
PubMed2004

Swelling dynamics of constrained thin-plate gels under an external force.

We analyze the swelling kinetics of constrained thin-plate gels using the linearized stress-diffusion coupling model proposed in the previous paper [Phys. Rev. E 69, 041402 (2004)]]. The gel is chemically clamped on the disk-like glass plates at the top and the bottom surfaces and can swell and shrink only along the thickness direction. We analyze how the top plate moves when a force is applied at a certain point on the top plate while the bottom plate is fixed. We predict that (i) the translation and the rotation of the top plate are described by a single exponential relaxation process, that (ii) the rotational relaxation process is three times faster than the translational one, and that (iii) when the force is applied to the edge, the displacement by the rotation is four times larger than that by the translation at the edge point where the force is applied. We also analyze how the gel deforms when it is clamped on the flexible film on which external load is applied.

Journal Article↗