Charge effects on the hindered transport of macromolecules across the endothelial surface glycocalyx layer

A fluid mechanical and electrostatic model for the transport of solute molecules across the vascular endothelial surface glycocalyx layer (EGL) was developed to study the charge effect on the diffusive and convective transport of the solutes. The solute was assumed to be a spherical particle with a constant surface charge density, and the EGL was represented as an array of periodically arranged circular cylinders of like charge, with a constant surface charge density. By combining the fluid mechanical analyses for the flow around a solute suspended in an electrolyte solution and the electrostatic analyses for the free energy of the interaction between the solute and cylinders based on a mean field theory, we estimated the transport coefficients of the solute across the EGL. Both of diffusive and convective transports are reduced compared to those for an uncharged system, due to the stronger exclusion of the solute that results from the repulsive electrostatic interaction. The model prediction for the reflection coefficient for serum albumin agreed well with experimental observations if the charge density in the EGL is ranged from approximately -10 to -30 mEq/l.

Human aquaporins:regulators of transcellular water flow

Background - Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistent with their expression in most tissues, AQPs are associated with diverse physiological and pathophysiological processes. Scope of review - AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell volume regulation (CVR) is particularly notable. This review examines the regulatory role of AQPs in transcellular water flow, especially in CVR. We focus on key systems of the human body, encompassing processes as diverse as urine concentration in the kidney to clearance of brain oedema. Major conclusions - AQPs are crucial for the regulation of water homeostasis, providing selective pores for the rapid movement of water across diverse cell membranes and playing regulatory roles in CVR. Gating mechanisms have been proposed for human AQPs, but have only been reported for plant and microbial AQPs. Consequently, it is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane water permeability and a regulator of transcellular water flow. General significance - Elucidating the mechanisms that regulate transcellular water flow will improve our understanding of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins.

Self-assembly of cross-linked β-cyclodextrin nanocapsules

Stirring of perthiolated β-cyclodextrin in water yields cross-linked hollow capsules ca. 50 nm in diameter, which can be used for encapsulation and controlled release of large molecules as shown using Reichardt's dye. © 2009 The Royal Society of Chemistry.

Experiments for CFD-modelling of cooling water and Insulation debris two-phase flow phenomena during loss of coolant accidents

The knowledge of insulation debris generation and transport gains in importance regarding reactor safety research for PWR and BWR. The insulation debris released near the break consists of a mixture of very different fibres and particles concerning size, shape, consistence and other properties. Some fraction of the released insulation debris will be transported into the reactor sump where it may affect emergency core cooling. Experiments are performed to blast original samples of mineral wool insulation material by steam under original thermal-hydraulic break conditions of BWR. The gained fragments are used as initial specimen for further experiments at acrylic glass test facilities. The quasi ID-sinking behaviour of the insulation fragments are investigated in a water column by optical high speed video techniques and methods of image processing. Drag properties are derived from the measured sinking velocities of the fibres and observed geometric parameters for an adequate CFD modelling. In the test rig "Ring line-II" the influence of the insulation material on the head loss is investigated for debris loaded strainers. Correlations from the filter bed theory are adapted with experimental results and are used to model the flow resistance depending on particle load, filter bed porosity and parameters of the coolant flow. This concept also enables the simulation of a particular blocked strainer with CFDcodes. During the ongoing work further results of separate effect and integral experiments and the application and validation of the CFD-models for integral test facilities and original containment sump conditions are expected.

Verification and validation of numerical models of the transport of insulation debris

A combination of the two-fluid and drift flux models have been used to model the transport of fibrous debris. This debris is generated during loss of coolant accidents in the primary circuit of pressurized or boiling water nuclear reactors, as high pressure steam or water jets can damage adjacent insulation materials including mineral wool blankets. Fibre agglomerates released from the mineral wools may reach the containment sump strainers, where they can accumulate and compromise the long-term operation of the emergency core cooling system. Single-effect experiments of sedimentation in a quiescent rectangular column and sedimentation in a horizontal flow are used to verify and validate this particular application of the multiphase numerical models. The utilization of both modeling approaches allows a number of pseudocontinuous dispersed phases of spherical wetted agglomerates to be modeled simultaneously. Key effects on the transport of the fibre agglomerates are particle size, density and turbulent dispersion, as well as the relative viscosity of the fluid-fibre mixture.

Paediatric drug development:reformulation, in vitro, genomic and in vivo evaluation

Angiotensin converting enzyme (ACE) inhibitors lisinopril and ramipril were selected from EMA/480197/2010 and the potassium-sparing diuretic spironolactone was selected from the NHS specials list for November 2011 drug tariff with the view to produce oral liquid formulations providing dosage forms targeting paediatrics. Lisinopril, ramipril and spironolactone were chosen for their interaction with transporter proteins in the small intestine. Formulation limitations such as poor solubility or pH sensitivity needed consideration. Lisinopril was formulated without extensive development as drug and excipients were water soluble. Ramipril and spironolactone are both insoluble in water and strategies combating this were employed. Ramipril was successfully solubilised using low concentrations of acetic acid in a co-solvent system and also via complexation with hydroxypropyl-β-cyclodextrin. A ramipril suspension was produced to take formulation development in a third direction. Spironolactone dosages were too high for solubilisation techniques to be effective so suspensions were developed. A buffer controlled pH for the sensitive drug whilst a precisely balanced surfactant and suspending agent mix provided excellent physical stability. Characterisation, stability profiling and permeability assessment were performed following formulation development. The formulation process highlighted current shortcomings in techniques for taste assessment of pharmaceutical preparations resulting in early stage research into a novel in vitro cell based assay. The formulations developed in the initial phase of the research were used as model formulations investigating microarray application in an in vitro-in vivo correlation for carrier mediated drug absorption. Caco-2 cells were assessed following transport studies for changes in genetic expression of the ATP-binding cassette and solute carrier transporter superfamilies. Findings of which were compared to in vitro and in vivo permeability findings. It was not possible to ascertain a correlation between in vivo drug absorption and the expression of individual genes or even gene families, however there was a correlation (R2 = 0.9934) between the total number of genes with significantly changed expression levels and the predicted human absorption.

Beyond water homeostasis:diverse functional roles of mammalian aquaporins

Background - Aquaporin (AQP) water channels are best known as passive transporters of water that are vital for water homeostasis. Scope of review - AQP knockout studies in whole animals and cultured cells, along with naturally occurring human mutations suggest that the transport of neutral solutes through AQPs has important physiological roles. Emerging biophysical evidence suggests that AQPs may also facilitate gas (CO2) and cation transport. AQPs may be involved in cell signalling for volume regulation and controlling the subcellular localization of other proteins by forming macromolecular complexes. This review examines the evidence for these diverse functions of AQPs as well their physiological relevance. Major conclusions - As well as being crucial for water homeostasis, AQPs are involved in physiologically important transport of molecules other than water, regulation of surface expression of other membrane proteins, cell adhesion, and signalling in cell volume regulation. General significance - Elucidating the full range of functional roles of AQPs beyond the passive conduction of water will improve our understanding of mammalian physiology in health and disease. The functional variety of AQPs makes them an exciting drug target and could provide routes to a range of novel therapies.

Impact of Water Supply and Sanitation on Diarrheal Morbidity among Young Children in the Socioeconomic and Cultural Context of Rwanda (Africa)

This project studied the frequency and of water contamination at the source, during transportation, and at home to determine the causes of contamination and its impact on the health of children aged 0 to 5 years. The methods used were construction of the infrastructure for three sources of potable water, administration of a questionnaire about socioeconomic status and sanitation behavior, anthropometric measurement of children, and analysis of water and feces. The contamination, first thought to be only a function of rainfall, turned out to be a very complex phenomenon. Water in homes was contaminated (43.4%) with more than 1100 total coliforms/100 ml due to the use of unclean utensils to transport and store water. This socio-economic and cultural problem should be ad- dressed with health education about sanitation, The latrines (found in 43.8% of families) presented a double-edged problem. The extremely high population density reduced the surface area of land per family, which resulted in a severe nutritional deficit (15% of the children) affecting mainly young children, rendering them more susceptible to diarrhea (three episodes/child/year).

Development of a mathematical and computer model to assess water quality impacts of hazardous compounds from minor gasoline spills in the inter-tidal zone of the Miami River, Florida

The objective of this study was to develop a model to predict transport and fate of gasoline components of environmental concern in the Miami River by mathematically simulating the movement of dissolved benzene, toluene, xylene (BTX), and methyl-tertiary-butyl ether (MTBE) occurring from minor gasoline spills in the inter-tidal zone of the river. Computer codes were based on mathematical algorithms that acknowledge the role of advective and dispersive physical phenomena along the river and prevailing phase transformations of BTX and MTBE. Phase transformations included volatilization and settling. ^ The model used a finite-difference scheme of steady-state conditions, with a set of numerical equations that was solved by two numerical methods: Gauss-Seidel and Jacobi iterations. A numerical validation process was conducted by comparing the results from both methods with analytical and numerical reference solutions. Since similar trends were achieved after the numerical validation process, it was concluded that the computer codes algorithmically were correct. The Gauss-Seidel iteration yielded at a faster convergence rate than the Jacobi iteration. Hence, the mathematical code was selected to further develop the computer program and software. The model was then analyzed for its sensitivity. It was found that the model was very sensitive to wind speed but not to sediment settling velocity. ^ A computer software was developed with the model code embedded. The software was provided with two major user-friendly visualized forms, one to interface with the database files and the other to execute and present the graphical and tabulated results. For all predicted concentrations of BTX and MTBE, the maximum concentrations were over an order of magnitude lower than current drinking water standards. It should be pointed out, however, that smaller concentrations than the latter reported standards and values, although not harmful to humans, may be very harmful to organisms of the trophic levels of the Miami River ecosystem and associated waters. This computer model can be used for the rapid assessment and management of the effects of minor gasoline spills on inter-tidal riverine water quality. ^

Natural organic matter and colloid-facilitated arsenic transport and transformation in porous soil media

Prediction of arsenic transport and transformation in soil environment requires understanding the transport mechanisms and proper estimation of arsenic partitioning tong all three phases in soil/aquifer systems: mobile colloids, mobile soil solution, and immobile soil solids. The primary purpose of this research is to study natural dissolved organic matter (DOM)/colloid-facilitated transport of arsenic and understand the role of soil derived carriers in the transport and transformation of both inorganic and organoarsenicals in soils. ^ DOM/colloid facilitated arsenic transport and transformation in porous soil media were investigated using a set of experimental approaches including batch experiment, equilibrium membrane dialysis experiment and column experiment. Soil batch experiment was applied to investigate arsenic adsorption on a variety of soils with different characteristics; Equilibrium membrane dialysis was employed to determine the 'free' and 'colloid-bound/complexed' arsenic in water extracts of chosen soils; Column experiments were also set up in the laboratory to simulate arsenic transport and transformation through golf course soils in the presence and absence of soil-derived dissolved substances. ^ The experimental results revealed that organic matter amendments effectively reduced soil arsenic adsorption. The majority of arsenic present in the soil extracts was associated with small substances of molecular weight (MW) between 500 and 3,500 Da, Only a small fraction of arsenic was associated with higher MW substances (MW > 3,500 Da), which was operationally defined as colloidal part in this study. The association of arsenic and DOM in the soil extracts strongly affected arsenic bioavailability, arsenic transport and transformation in soils. The results of column experiments revealed arsenic complicated behavior with various processes occurring in soils studied, including: soil arsenic' adsorption, facilitated arsenic transportation by dissolved substances presented in soil extracts and microorganisms involved arsenic species transformation. ^ Soil organic matter amendments effectively reduce soil arsenic adsorption capability either by scavenging 'soil arsenic adsorption sites or by interactions between arsenic species and dissolved organic chemicals in soil solution. Close attention must be paid for facilitated arsenic transport by dissolved substances presented in soil solution and microorganisms involved arsenic species transformation in arsenic-contaminated soils.^

High-resolution cyclostratigraphy of the Cenomanian-Turonian interval: Paleoceanographic implications, a comparison between deep sea drilling project site 386 and 144

The purpose of this study was to determine the extent to which oceanic anoxic events (OAE's) are recorded in deep-water deposits of the former western Tethyan Sea, by investigating the Cenomanian-Turonian time interval characterized by the worldwide OAE 2 event. The study improved our knowledge of the possible controlling mechanisms that triggered this event at these sites, and furthered our understanding of this global phenomenon. This was examined by high-resolution, multi-proxy analyses of sediments at DSDP Sites 386 and 144, including sedimentology, scanning electron microscopy, stable isotopes, bulk and clay mineralogy, major and trace element geochemistry, biomarkers, and paleontological data. ^ The results provide a better stratigraphic resolution for the Cenomanian-Turonian, which allowed for more precise determination of chronologic boundaries, sedimentation rates at DSDP Site 386, and a more accurate calculation of the frequency of the cycles recorded in the sequence, which fall predominantly within the precession (∼23 kyr) and short eccentricity (∼100 kyr) ranges. The combined proxies allow assessment of the correlation of δ13Corg, and major and trace elements with the predominance of cyanobacteria. These organisms were the main producers of the organic matter during the dysoxic and euxinic conditions of OAE 2 at DSDP Site 386. A huge amount of microcrystalline quartz of eolian origin is also associated with OAE 2. The geochemical proxies further provide evidence that OAE 2 was linked to increased volcanism outside the deep water of the proto-Atlantic Ocean. The clays in the Turonian sediments are terrigenous and derived predominantly from eolian transport. Comparing DSDP Site 386 and 144 with stratotype sections, the δ13C org and TOC data indicate that OAE 2 seems diachronous throughout the proto-Atlantic Ocean. ^ This study concludes that the development of anoxic conditions in the deep water of the Atlantic during the latest Cenomanian-Turonian resulted from a combination of factors related to local oceanic setting and mitigated by global tectonism and climate. The data provide a more comprehensive view of the interacting factors that led to sustained high productivity of the cyanobacteria and photosynthetic protists that produced organic-carbon-rich deposits in the world's oceans. ^

An integrated flow and transport model to study the impact of mercury remediation strategies for East Fork Poplar Creek watershed, Oak Ridge, Tennessee

An integrated flow and transport model using MIKE SHE/MIKE 11 software was developed to predict the flow and transport of mercury, Hg(II), under varying environmental conditions. The model analyzed the impact of remediation scenarios within the East Fork Poplar Creek watershed of the Oak Ridge Reservation with respect to downstream concentration of mercury. The numerical simulations included the entire hydrological cycle: flow in rivers, overland flow, groundwater flow in the saturated and unsaturated zones, and evapotranspiration and precipitation time series. Stochastic parameters and hydrologic conditions over a five year period of historical hydrological data were used to analyze the hydrological cycle and to determine the prevailing mercury transport mechanism within the watershed. Simulations of remediation scenarios revealed that reduction of the highly contaminated point sources, rather than general remediation of the contaminant plume, has a more direct impact on downstream mercury concentrations.

Water resources assessment and geographic information system (GIS)-based stormwater runoff estimates for artificial recharge of freshwater aquifers in New Providence, Bahamas

The Bahamas is a small island nation that is dealing with the problem of freshwater shortage. All of the country’s freshwater is contained in shallow lens aquifers that are recharged solely by rainfall. The country has been struggling to meet the water demands by employing a combination of over-pumping of aquifers, transport of water by barge between islands, and desalination of sea water. In recent decades, new development on New Providence, where the capital city of Nassau is located, has created a large area of impervious surfaces and thereby a substantial amount of runoff with the result that several of the aquifers are not being recharged. A geodatabase was assembled to assess and estimate the quantity of runoff from these impervious surfaces and potential recharge locations were identified using a combination of Geographic Information Systems (GIS) and remote sensing. This study showed that runoff from impervious surfaces in New Providence represents a large freshwater resource that could potentially be used to recharge the lens aquifers on New Providence.

Effects of climate variability on transparency and thermal structure in subtropical, monomictic Lake Annie, Florida

Lake Annie is a small (37 ha), relatively deep (21 m) sinkhole lake on the Lake Wales Ridge (LWR) of central Florida with a long history of study, including monthly limnological monitoring since June, 1983. The record shows high variability in Secchi disc transparency, which ranged from < 1 to 15 m with a trend toward decreasing values over the latter decade of record. We examined available regional meteorological, groundwater and limnological data to determine the drivers and thermal consequences of variability in water transparency. While total nutrient concentrations and chlorophyll-a were highest during years of low transparency, stepwise regression showed that none of these had a signifi cant effect on transparency after water color was taken into account. Repeated years of high precipitation between 1993–2005 caused an increase in water table height, increasing the transport of dissolved substances from the vegetated watershed into the lake. Groundwater stage explained 73 % of the interannual variability in water transparency. Transparency, in turn, explained 85 % of the interannual variability in the heat budget for the lake, which ranged from 1.8 × 108 to 4.1 × 108 Joules m–2 yr–1, encompassing the range reported across Florida lakes. While surface water temperature was not affected by transparency, depths below 5 m warmed faster during the stratifi ed period during years having a lower rate of light extinction. We show that an increase in precipitation of 20 cm per year reduces the depth of the summer euphotic zone and thermocline by 1.9 and 1.6 m, respectively, and causes a 1-month reduction in the duration of winter mixing in this monomictic lake. Because biota have been shown to respond to shifts in light and heat distribution of much smaller magnitude than exhibited here, our work suggests that subtle changes in precipitation linked to climate fl uctuations may have signifi cant physical as well as biotic consequences.

Multidecadal climate oscillations detected in a transparency record from a subtropical Florida lake

Synchronous interannual variability in water transparency observed in neighboring lakes has been linked to regional precipitation and resultant runoff of dissolved organic material, but many climate forcings oscillate over time scales longer than most limnological records can detect. A strong relationship (R2 5 0.86) between transparency and the previous two years’ rainfall and lake stage in a 25-yr record from a Florida lake enabled us to hindcast transparency from a longer 75-yr record of rainfall and lake stage. Predictions revealed a ,30-yr cycle in transparency linked to the Atlantic Multidecadal Oscillation (AMO). Transparency was greatest (4–8 m) in the cool phase of the AMO (,1962–1993) associated with below-average rainfall in south Florida and lowest (0.1– 3.0 m) during two warm phases (,1932–1961, 1994–present) associated with above-average, but more variable, annual rainfall. Models that predict effects of large-scale hydrologic restoration projects on solute export from South Florida’s expansive wetlands need to account for recent entry into a warm AMO phase, where teleconnections between the AMO phases and runoff are opposite of those shown for the U.S. interior.