The structural permeability of concrete at cryogenic temperatures

The thesis describes a programme of research designed to identify concretes for application at cryogenic temperature, in particular for storage of Liquefield Natural Gas which is maintained at a temperature of -165oC. The programme was undertaken in two stages. Stage 1 involved screening tests on seventeen concrete mixes to investigate the effects of strength grade (and water/cement ratio), air entrainment, aggregate type and cement type. Four mixes were selected on the basis of low temperature strength, residual strength after thermal cycling and permeability at ambient temperature. In Stage 2 the selected mixes were subjected to a comprehensive range of tests to measure those properties which determine the leak tightness of a concrete tank at temperatures down to -165oC. These included gas permeability; tensile strength, strain capacity, thermal expansion coefficient and elastic modulus, which in combination provide a measure of resistance to cracking; and bond to reinforcement, which is one of the determining factors regarding crack size and spacing. The results demonstrated that the properties of concrete were generally enhanced at cryogenic temperature, with reduced permeability, reduced crack proneness and, by virtue of increased bond to reinforcement, better control of cracking should it occur. Of the concretes tested, a lightweight mix containing sintered PFA aggregate exhibited the best performance at ambient and cryogenic temperature, having appreciably lower permeability and higher crack resistance than normal weight concretes of the same strength grade. The lightweight mix was most sensitive to thermal cycling, but there was limited evidence that this behaviour would not be significant if the concrete was prestressed. Relationships between various properties have been identified, the most significant being the reduction in gas permeability with increasing strain capacity. The structural implications of the changing properties of the concrete have also been considered.

Pore structure and diffusional properties of hardened cement pastes

This study has investigated the inclusion of pulverised fuel ash (PFA) and blast furnace slag (BFS) into hardened cement pastes (HCP) in retarding the ingress of chloride ions and oxygen molecules from the external environment. The influence of environmental factors such as drying and carbonation on the pore structure and diffusional properties of OPC, OPC/30%PFA and OPC/65%BFS hardened pastes was investigated. Specimens were desorbed from a saturated surface dry condition to a near constant weight at 65% relative humidity (RH) while others were simultaneously exposed to a 65% RH atmosphere and a carbon dioxide atmosphere of up to 5% by volume until there were fully carbonated. The presence of the interfacial zone at the cement paste-aggregate interface was critically reviewed and identified. The influence of the interfacial zone on porosity and chloride ingress in assumed periodic composites of glass bead mortars was also studied. The investigations have demonstrated the following: (a) The use of fly ash and slag in blended cement pastes has resulted in a marked reduction in capillary porosity and rate of chloride ingress. (b) The ratio of oxygen to chloride diffusion coefficients increased from values close to 1 in permeable pastes, to values of around 15 in low-permeability blended fly ash and slag pastes. This supports the view that the diffusion of chloride ions is retarded by the surface charge of the hydrated cement gel in low-permeability pastes. (c) Compared with plain OPC pastes, the carbonation of blended fly ash and slag pastes resulted in a marked increase in the coarse capillary porosity and a corresponding increase in the oxygen and chloride diffusion rates.

Paracellular permeability is increased by basal lipopolysaccharide in a primary culture of colonic epithelial cells; an effect prevented by an activator of Toll-like receptor-2

Lipopolysaccharide (LPS), which generally activates Toll-like receptor 4 (TLR4), is expressed on commensal colonic bacteria. In a number of tissues, LPS can act directly on epithelial cells to increase paracellular permeability. Such an effect in the colon would have an important impact on the understanding of normal homeostasis and of pathology. Our aim was to use a novel primary culture of colonic epithelial cells grown on Transwells to investigate whether LPS, or Pam(3)CSK( 4), an activator of TLR2, affected paracellular permeability. Consequently, [(14)C]-mannitol transfer and transepithelial electrical resistance (TEER) were measured. The preparation consisted primarily of cytokeratin-18 positive epithelial cells that produced superoxide, stained for mucus with periodic acid-Schiff reagent, exhibited alkaline phosphatase activity and expressed TLR2 and TLR4. Tight junctions and desmosomes were visible by transmission electron microscopy. Basally, but not apically, applied LPS from Escherichia coli increased the permeability to mannitol and to a 10-kDa dextran, and reduced TEER. The LPS from Helicobacter pylori increased paracellular permeability of gastric cells when applied either apically or basally, in contrast to colon cells, where this LPS was active only from the basal aspect. A pan-caspase inhibitor prevented the increase in caspase activity caused by basal E. coli LPS, and reduced the effects of LPS on paracellular permeability. Synthetic Pam(3)CSK(4) in the basal compartment prevented all effects of basal E. coli LPS. In conclusion, LPS applied to the base of the colonic epithelial cells increased paracellular permeability by a mechanism involving caspase activation, suggesting a process by which perturbation of the gut barrier could be exacerbated. Moreover, activation of TLR2 ameliorated such effects.

Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability

Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows.

Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides

BACKGROUND & AIMS: The transferrin receptor (CD71) is up-regulated in duodenal biopsy samples from patients with active celiac disease and promotes retrotransport of secretory immunolglobulin A (SIgA)-gliadin complexes. We studied intestinal epithelial cell lines that overexpress CD71 to determine how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides. METHODS: We analyzed duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. Caco-2 and HT29-19A epithelial cell lines were transfected with fluorescence-labeled small interfering RNAs against CD71. Interactions among IgA, CD71, and transglutaminase 2 (Tgase2) were analyzed by flow cytometry, immunoprecipitation, and confocal microscopy. Transcytosis of SIgACD71 complexes and intestinal permeability to the gliadin 3H-p3149 peptide were analyzed in polarized monolayers of Caco-2 cells. RESULTS: Using fluorescence resonance energy transfer and in situ proximity ligation assays, we observed physical interactions between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells. CD71 and Tgase2 were co-precipitated with SIgA, bound to the surface of Caco-2 cells. SIgACD71 complexes were internalized and localized in early endosomes and recycling compartments but not in lysosomes. In the presence of celiac IgA or SIgA against p3149, transport of intact 3H-p3149 increased significantly across Caco-2 monolayers; this transport was inhibited by soluble CD71 or Tgase2 inhibitors. CONCLUSIONS: Upon binding to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apicalbasal transcytosis of bound peptides. This mechanism is facilitated by Tgase2 and might be involved in the pathogenesis of celiac disease.

Permeability characteristics of temozolomide and its ester and amide products through rat and human skin.

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On the effect of blue staining fungi on the permeability of sitka spruce

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High permeability of the anionic form restricts accumulation of indomethacin by cultured gastric surface epithelial cells exposed to low apical pH

The 'ion-trapping' hypothesis suggests that the intracellular concentration of acidic non-steroidal anti-inflammatory drugs in gastric epithelial cells could be much higher than in the gastric lumen, and that such accumulation could contribute to their gastrotoxicity. Our aim was to examine the effect of the pH of the apical medium on the apical to basal transfer of the acidic drug indomethacin (pK a 4.5) across a gastric mucous epithelial cell monolayer, and to determine whether indomethacin accumulated in cells exposed to a low apical pH. Guinea-pig gastric mucous epithelial cells were grown on porous membrane culture inserts (Transwells®) for 72 h. Transfer and accumulation of [ 14C] indomethacin were assessed by scintillation counting. Transfer of [ 3H]mannitol and measurement of trans-epithelial electrical resistance were used to assess integrity of the monolayer. Distribution of [ 14C] urea was used to estimate the intracellular volume of the monolayer. The monolayer was not disrupted by exposure of the apical face to media of pH ≥ 3, or by indomethacin. Transfer of indomethacin (12 μM) to the basal medium increased with decreasing apical medium pH. The apparent permeability of the undissociated acid was estimated to be five times that of the anion. The intracellular concentration of indomethacin was respectively 5.3, 4.1 and 4.3 times that in the apical medium at pH 5.5, 4.5 and 3.0. In conclusion, this study represents the first direct demonstration that indomethacin accumulates in gastric epithelial cells exposed to low apical pH. However, accumulation of indomethacin was moderate and the predictions of the ion-trapping hypothesis were not met, probably due to the substantial permeability of anionic indomethacin across membranes. © 2006 Elsevier B.V. All rights reserved.

Noncovalent coatings for the separation of synthetic polypeptides by nonaqueous capillary electrophoresis

Recently, we demonstrated the possibility to extend the range of capillary electrophoresis (CE) applications to the separation of non-water-soluble synthetic polymers. This work focuses on the control of the electro-osmotic flow (EOF) and on the limitation of the solute adsorption in nonaqueous electrolytes. For these purposes, different strategies were investigated. For the initial, a viscous additive (ethylene glycol or glycerol) was used in the electrolyte in order to decrease the EOF magnitude and, possibly, to compete with solute adsorption. A second strategy was to modify, before separation, the fused-silica capillary wall by the adsorption of poly(ethylene oxide) (PEO) via hydrogen bonding. The influence of the molecular mass of the adsorbed PEO on the EOF magnitude and direction was studied in electrolytes based on methanol/acetonitrile mixtures containing ammonium ions. For PEO molecular masses above 1000 g/mol, reversed (anodic) EOF were reported in accordance with previous results obtained with PEO covalently bonded capillaries. The influence of the nature and the concentration of the background electrolyte cation on the EOF magnitude and direction were also investigated. A third strategy consisted in modifying the capillary wall by the adsorption of a cationic polyelectrolyte layer. Advantageously, this polyelectrolyte layer suppressed the adsorption of the polymer solutes onto the capillary wall. The results obtained in this work confirm the high potential and the versatility of CE for the characterization of ionizable organic polymers in nonaqueous media.

Nonaqueous capillary zone electrophoresis of synthetic organic polypeptides

Poly(Nε-trifluoroacetyl-l-lysine) was used as a model solute to investigate the potential of nonaqueous capillary electrophoresis (NACE) for the characterization of synthetic organic polymers. The information obtained by NACE was compared to that derived from size exclusion chromatography (SEC) experiments, and the two techniques were found to be complimentary for polymer characterization. On one hand, NACE permitted (i) the separation of oligomers according to their molar mass and (ii) the separation of the polymers according to the nature of the end groups. On the other hand, SEC experiments were used for the characterization of the molar mass distribution for higher molar masses. Due to the tendency of the solutes (polypeptides) to adsorb onto the fused-silica capillary wall, careful attention was paid to the rinsing procedure of the capillary between runs in order to keep the capillary surface clean. For that purpose, the use of electrophoretic desorption under denaturating conditions was very effective. Optimization of the separation was performed by studying (i) the influence of the proportion of methanol in a methanol/acetonitrile mixture and (ii) the influence of acetic acid concentration in the background electrolyte. Highly resolved separation of the oligomers (up to a degree of polymerization n of ∼50) was obtained by adding trifluoroacetic acid to the electrolyte. Important information concerning the polymer conformations could be obtained from the mobility data. Two different plots relating the effective mobility data to the degree of polymerization were proposed for monitoring the changes in polymer conformations as a function of the number of monomers.

Genomic evaluation during permeability of indomethacin and its solid dispersion

Drug resistance was first identified in cancer cells that express proteins known as multidrug resistance proteins that extrude the therapeutic agents out of the cells resulting in alteration of pharmacokinetics, tissue distribution, and pharmacodynamics of drugs. To this end studies were carried out to investigate the role of pharmacological inhibitors and pharmaceutical excipients with a primary focus on P-glycoprotein (P-gp). The aim of this study was to investigate holistic changes in transporter gene expression during permeability upon formulation of indomethacin as solid dispersion. Initial characterization studies of solid dispersion of indomethacin showed that the drug was dispersed within the carrier in amorphous form. Analysis of permeability data across Caco-2 monolayers revealed that drug absorption increased by 4-fold when reformulated as solid dispersion. The last phase of the work involved investigation of gene expression changes of transporter genes during permeability. The results showed that there were significant differences in the expression of both ATP-binding cassette (ABC) transporter genes as well as solute carrier transporter (SLC) genes suggesting that the inclusion of polyethylene glycol as well as changes in molecular form of drug from crystalline to amorphous have a significant bearing on the expression of transporter network genes resulting in differences in drug permeability. © 2011 Informa UK, Ltd.

Rutting-induced permeability loss of open graded friction course mixtures

Functionality of an open graded friction course (OGFC) depends on the high interconnected air voids or pores of the OGFC mixture. The authors' previous study indicated that the pores in the OGFC mixture were easily clogged by rutting deformation. Such a deformation-related clogging can cause a significant rutting-induced permeability loss in the OGFC mixture. The objective of this study was to control and reduce the rutting-induced permeability loss of the OGFC based on mixture design and layer thickness. Eight types of the OGFC mixtures with different air void contents, gradations, and nominal maximum aggregate sizes were fabricated in the laboratory. Wheel-tracking rutting tests were conducted on the OGFC slabs to simulate the deformation-related clogging. Permeability tests after different wheel load applications were performed on the rutted OGFC slabs using a falling head permeameter developed in the authors' previous study. The relationships between permeability loss and rutting depth as well as dynamic stability were developed based on the eight OGFC mixtures' test results. The thickness effects of the single-layer and the two-layer OGFC slabs were also discussed in terms of deformation-related clogging and the rutting-induced permeability loss. Results showed that the permeability coefficient decreases linearly with an increasing rutting depth of the OGFC mixtures. Rutting depth was recommended as a design index to control permeability loss of the OGFC mixture rather than the dynamic stability. Permeability loss due to deformation-related clogging can be effectively reduced by using a thicker single-layer OGFC or two-layer OGFC.

Modified lipids from LDL in the blood during mid-life increase blood brain barrier permeability

Low density lipoprotein levels (LDL) are consistently elevated in cardiovascular disease. It has been suggested that those with high circulating LDL levels in mid-life may be susceptible to develop neurodegenerative diseases in later life. In the circulation, high levels of LDL are associated with increased oxidative modification (oxLDL) and nitration. We have investigated the hypothesis that disruption of blood brain barrier function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention in mid-life can mitigate the neurodegenerative effects of hyperlipidaemia. Blood from statin-naïve, normo- and hyperlipidaemic subjects (n=10/group) was collected at baseline. Hyperlipidaemic subjects received statin-intervention whereas normolipidaemic subjects did not prior to a second blood sampling, taken after 3 months. The intervention will be completed in June 2013. Plasma was separated by centrifugation (200g, 30min) and LDL was isolated by potassium bromide density gradient ultracentrifugation. Total homocysteine, LDL cholesterol, 8-isoprostane F2α levels were measured in plasma using commercial kits. LDL were analysed by agarose gel electrophoresis. LDL-lipids were extracted by partitioning in 1:1 chloroform:methanol (v/v) and conjugated to fatty acid free-BSA in serum-free EGM-2 medium (4hrs, 370C) for co-culture with human microvascular endothelial cells (HMVEC). HMVEC were maintained on polycarbonate inserts for two weeks to create a microvascular barrier. Change in barrier permeability was measured by trans-endothelial electrical resistance (TER), FITC-dextran permeability and immunohistochemistry. HMVEC glutathione (GSH) levels were measured after 2 hours by GSH-glo assay. LDL isolated from statin-naïve hyperlipidaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and plasma 8-isoprostane F2α (43.5±8.42 pg/ml) compared to control subjects (0.46±0.05 and 24.2±5.37 pg/ml; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5μM) from normolipidaemic subjects, LDL-lipids from hyperlipidaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased GSH (18.5 nmol/mg v 12.3 nmol/mg; untreated cells 26.2±3.6 nmol/mg).

On the hydrothermal stability of MCM-41. Evidence of capillary tension-induced effects

MCM-41's limited hydrothermal stability has been often related to the hydrolysis of Si-O-Si bonds due to the low degree of condensation, its thin walls or a combination of them. In this work, evidence for an additional factor is provided; a physical effect that occurs during the drying of the hydrothermally treated calcined material due to the intense capillary stress exerted in water. Depending on both physical (i.e. mechanical) and chemical (i.e. hydrolysis) resistances, the structure undergoes differently. Three MCM-41 samples with different degree of condensation were investigated. The most remarkable results are found with un-aged TEOS based material, which gets fully disordered and shrunk for all applied hydrothermal temperatures in water. Comparison between water and a low-surface-tension-solvent drying revealed that capillarity is responsible for the loss of ordering (and shrinkage) at moderate hydrothermal temperatures. The material's structure is hexagonal and shrinkage-free under the low-surface-tension-solvent route. At a high hydrothermal temperature, hydrolysis is extensive and responsible for the loss of ordering. The other remarkable finding regards the aged MCM-41 mesostructure that maintains the hexagonal features at all applied temperatures in water, and it is more stable against capillarity at high temperature. The Na-metasilicate based material is mechanically very stable and gets disordered at high temperature due to hydrolysis.

Capillary siphons and their application in the fuel delivery system of direct methanol fuel cells

The objective of the work is to develop a fuel delivery system for potable direct methanol fuel cell. Currently, one of the most fundamental limitations of direct methanol fuel cells is that the fuel supplied to the anode of the DMFC must be a very dilute aqueous methanol solution (usually 0.5∼1.5 M). If a DMFC is filled with a dilute aqueous methanol solution, the fuel cell operation time per refuel would be very short, which would considerably diminish the advantage of a DMFC over a conventional battery. To overcome this difficulty, a complex fuel delivery system based on the modern micro system technology was proposed by the author. The proposed fuel delivery system would include micro-pumps, a methanol sensor, and a control unit. The fuel delivery system adds considerable costs to the fuel cell system and consume considerable amount of electricity from the fuel cell, which in turn significantly reduces the net power output of the fuel cell. As a result, the DMFC would have tremendous difficulty to compete with the conventional battery technology in terms of costs and power output. ^ This work presents a novel passive fuel delivery system for direct methanol fuel cells. In this particular system, a methanol fuel and an aqueous methanol solution are stored separately in two containers and a wick is disposed between the two containers in a siphon fashion, with the container of the aqueous methanol solution communicating with the anode of the DMFC. Methanol is siphoned from the methanol container to the aqueous solution container in-situ when the methanol in the aqueous methanol solution is consumed during the operation of the fuel cell. Through a proper selection of the wick and the containers, the methanol concentration near the anode of the DMFC could be maintained within a preferable range. ^