Metabolism in anoxic permeable sediments is dominated by eukaryotic dark fermentation

PubMed Central

Bourke, Michael F; Marriott, Philip J.; Glud, Ronnie N.; Hasler-Sheetal, Harald; Kamalanathan, Manoj; Beardall, John; Greening, Chris; Cook, Perran L.M.

2016-01-01

Permeable sediments are common across continental shelves and are critical contributors to marine biogeochemical cycling. Organic matter in permeable sediments is dominated by microalgae, which as eukaryotes have different anaerobic metabolic pathways to prokaryotes such as bacteria and archaea. Here we present analyses of flow-through reactor experiments showing that dissolved inorganic carbon is produced predominantly as a result of anaerobic eukaryotic metabolic activity. In our experiments, anaerobic production of dissolved inorganic carbon was consistently accompanied by large dissolved H2 production rates, suggesting the presence of fermentation. The production of both dissolved inorganic carbon and H2 persisted following administration of broad spectrum bactericidal antibiotics, but ceased following treatment with metronidazole. Metronidazole inhibits the ferredoxin/hydrogenase pathway of fermentative eukaryotic H2 production, suggesting that pathway as the source of H2 and dissolved inorganic carbon production. Metabolomic analysis showed large increases in lipid production at the onset of anoxia, consistent with documented pathways of anoxic dark fermentation in microalgae. Cell counts revealed a predominance of microalgae in the sediments. H2 production was observed in dark anoxic cultures of diatoms (Fragilariopsis sp.) and a chlorophyte (Pyramimonas) isolated from the study site, substantiating the hypothesis that microalgae undertake fermentation. We conclude that microalgal dark fermentation could be an important energy-conserving pathway in permeable sediments. PMID:28070216

Formation of magmatic brine lenses via focussed fluid-flow beneath volcanoes

NASA Astrophysics Data System (ADS)

Afanasyev, Andrey; Blundy, Jon; Melnik, Oleg; Sparks, Steve

2018-03-01

Many active or dormant volcanoes show regions of high electrical conductivity at depths of a few kilometres beneath the edifice. We explore the possibility that these regions represent lenses of high-salinity brine separated from a single-phase magmatic fluid containing H2O and NaCl. Since chloride-bearing fluids are highly conductive and have an exceptional capacity to transport metals, these regions can be an indication of an active hydrothermal ore-formation beneath volcanoes. To investigate this possibility we have performed hydrodynamic simulations of magma degassing into permeable rock. In our models the magma source is located at 7 km depth and the fluid salinity approximates that expected for fluids released from typical arc magmas. Our model differs from previous models of a similar process because it is (a) axisymmetric and (b) includes a static high-permeability pathway that links the magma source to the surface. This pathway simulates the presence of a volcanic conduit and/or plexus of feeder dykes that are typical of most volcanic systems. The presence of the conduit leads to a number of important hydrodynamic consequences, not observed in previous models. Importantly, we show that an annular brine lens capped by crystallised halite is likely to form above an actively degassing sub-volcanic magma body and can persist for more than 250 kyr after degassing ceases. Parametric analysis shows that brine lenses are more prevalent when the fluid is released at temperatures above the wet granite solidus, when magmatic fluid salinity is high, and when the high-permeability pathway is narrow. The calculated depth, form and electrical conductivity of our modelled system shares many features with published magnetotelluric images of volcano subsurfaces. The formation and persistence of sub-volcanic brine lenses has implications for geothermal systems and hydrothermal ore formation, although these features are not explored in the presented model.

The regulation of vascular endothelial growth factor-induced microvascular permeability requires Rac and reactive oxygen species.

PubMed

Monaghan-Benson, Elizabeth; Burridge, Keith

2009-09-18

Vascular permeability is a complex process involving the coordinated regulation of multiple signaling pathways in the endothelial cell. It has long been documented that vascular endothelial growth factor (VEGF) greatly enhances microvascular permeability; however, the molecular mechanisms controlling VEGF-induced permeability remain unknown. Treatment of microvascular endothelial cells with VEGF led to an increase in reactive oxygen species (ROS) production. ROS are required for VEGF-induced permeability as treatment with the free radical scavenger, N-acetylcysteine, inhibited this effect. Additionally, treatment with VEGF caused ROS-dependent tyrosine phosphorylation of both vascular-endothelial (VE)-cadherin and beta-catenin. Rac1 was required for the VEGF-induced increase in permeability and adherens junction protein phosphorylation. Knockdown of Rac1 inhibited VEGF-induced ROS production consistent with Rac lying upstream of ROS in this pathway. Collectively, these data suggest that VEGF leads to a Rac-mediated generation of ROS, which, in turn, elevates the tyrosine phosphorylation of VE-cadherin and beta-catenin, ultimately regulating adherens junction integrity.

The impacts of effective stress and CO 2 sorption on the matrix permeability of shale reservoir rocks [The impacts of CO 2 sorption and effective stress on the matrix permeability of shale reservoir rocks

DOE PAGES

Wu, Wei; Zoback, Mark D.; Kohli, Arjun H.

2017-05-02

We assess the impacts of effective stress and CO 2 sorption on the bedding-parallel matrix permeability of the Utica shale through pressure pulse-decay experiments. We first measure permeability using argon at relatively high (14.6 MPa) and low (2.8 MPa) effective stresses to assess both pressure dependence and recoverability. We subsequently measure permeability using supercritical CO 2 and again using argon to assess changes due to CO 2 sorption. We find that injection of both argon and supercritical CO 2 reduces matrix permeability in distinct fashion. Samples with permeability higher than 10 –20 m 2 experience a large permeability reduction aftermore » treatment with argon, but a minor change after treatment with supercritical CO 2. However, samples with permeability lower than this threshold undergo a slight change after treatment with argon, but a dramatic reduction after treatment with supercritical CO 2. These results indicate that effective stress plays an important role in the evolution of relatively permeable facies, while CO 2 sorption dominates the change of ultra-low permeability facies. The permeability reduction due to CO 2 sorption varies inversely with initial permeability, which suggests that increased surface area from hydraulic stimulation with CO 2 may be counteracted by sorption effects in ultra-low permeability facies. As a result, we develop a conceptual model to explain how CO 2 sorption induces porosity reduction and volumetric expansion to constrict fluid flow pathways in shale reservoir rocks.« less

The impacts of effective stress and CO 2 sorption on the matrix permeability of shale reservoir rocks [The impacts of CO 2 sorption and effective stress on the matrix permeability of shale reservoir rocks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Wei; Zoback, Mark D.; Kohli, Arjun H.

We assess the impacts of effective stress and CO 2 sorption on the bedding-parallel matrix permeability of the Utica shale through pressure pulse-decay experiments. We first measure permeability using argon at relatively high (14.6 MPa) and low (2.8 MPa) effective stresses to assess both pressure dependence and recoverability. We subsequently measure permeability using supercritical CO 2 and again using argon to assess changes due to CO 2 sorption. We find that injection of both argon and supercritical CO 2 reduces matrix permeability in distinct fashion. Samples with permeability higher than 10 –20 m 2 experience a large permeability reduction aftermore » treatment with argon, but a minor change after treatment with supercritical CO 2. However, samples with permeability lower than this threshold undergo a slight change after treatment with argon, but a dramatic reduction after treatment with supercritical CO 2. These results indicate that effective stress plays an important role in the evolution of relatively permeable facies, while CO 2 sorption dominates the change of ultra-low permeability facies. The permeability reduction due to CO 2 sorption varies inversely with initial permeability, which suggests that increased surface area from hydraulic stimulation with CO 2 may be counteracted by sorption effects in ultra-low permeability facies. As a result, we develop a conceptual model to explain how CO 2 sorption induces porosity reduction and volumetric expansion to constrict fluid flow pathways in shale reservoir rocks.« less

Aquaglyceroporins Are the Entry Pathway of Boric Acid in Trypanosoma brucei.

PubMed

Marsiccobetre, Sabrina; Rodríguez-Acosta, Alexis; Lang, Florian; Figarella, Katherine; Uzcátegui, Néstor L

2017-05-01

The boron element possesses a range of different effects on living beings. It is essential to beneficial at low concentrations, but toxic at excessive concentrations. Recently, some boron-based compounds have been identified as promising molecules against Trypanosoma brucei, the causative agent of sleeping sickness. However, until now, the boron metabolism and its access route into the parasite remained elusive. The present study addressed the permeability of T. brucei aquaglyceroporins (TbAQPs) for boric acid, the main natural boron species. To this end, the three TbAQPs were expressed in Saccharomyces cerevisiae and Xenopus laevis oocytes. Our findings in both expression systems showed that all three TbAQPs are permeable for boric acid. Especially TbAQP2 is highly permeable for this compound, displaying one of the highest conductances reported for a solute in these channels. Additionally, T. brucei aquaglyceroporin activities were sensitive to pH. Taken together, these results establish that TbAQPs are channels for boric acid and are highly efficient entry pathways for boron into the parasite. Our findings stress the importance of studying the physiological functions of boron and their derivatives in T. brucei, as well as the pharmacological implications of their uptake by trypanosome aquaglyceroporins. Copyright © 2017 Elsevier B.V. All rights reserved.

Transport characteristics of urea transporter-B.

PubMed

Yang, Baoxue

2014-01-01

UT-B represents the major urea transporter in erythrocytes, in addition to being expressed in kidney descending vasa recta, brain, spleen, ureter, bladder, and testis. Expression of urea transporter UT-B confers high urea permeability to mammalian erythrocytes. Erythrocyte membranes are also permeable to various urea analogues, suggesting common transport pathways for urea and structurally similar solutes. UT-B is highly permeable to urea and the chemical analogues formamide, acetamide, methylurea, methylformamide, ammonium carbamate, and acrylamide, each with a Ps > 5.0 × 10(-6) cm/s at 10 °C. The amides formamide, acetamide, acrylamide, and butyramide efficiently diffuse across lipid bilayers. The urea analogues dimethylurea, acryalmide, methylurea, thiourea, and methylformamide inhibit UT-B-mediated urea transport by >60 % by a pore-blocking mechanism. UT-B is also a water channel in erythrocytes and has a single-channel water permeability that is similar to aquaporin-1. Whether UT-B is an NH3 channel still needs further study. Urea permeability (Purea) in erythrocytes differs between different mammals. Carnivores (dog, fox, cat) exhibit high Purea. In contrast, herbivores (cow, donkey, sheep) show much lower Purea. Erythrocyte Purea in human and pig (omnivores) was intermediate. Rodents and lagomorphs (mouse, rat, rabbit) have Purea intermediate between carnivores and omnivores. Birds that do not excrete urea and do not express UT-B in their erythrocytes have very low values. In contrast to Purea, water permeability is relatively similar in all mammals studied. This chapter will provide information about the transporter characteristics of UT-B.

Effect of persistent high intraocular pressure on microstructure and hydraulic permeability of trabecular meshwork

NASA Astrophysics Data System (ADS)

Mei, Xi; Ren, Lin; Xu, Qiang; Zheng, Wei; Liu, Zhi-Cheng

2015-05-01

As the aqueous humor leaves the eye, it first passes through the trabecular meshwork (TM). Increased flow resistance in this region causes elevation of intraocular pressure (IOP), which leads to the occurrence of glaucoma. To quantitatively evaluate the effect of high IOP on the configuration and hydraulic permeability of the TM, second harmonic generation (SHG) microscopy was used to image the microstructures of the TM and adjacent tissues in control (normal) and high IOP conditions. Enucleated rabbit eyes were perfused at a pressure of 60 mmHg to achieve the high IOP. Through the anterior chamber of the eye, in situ images were obtained from different depths beneath the surface of the TM. Porosity and specific surface area of the TM in control and high IOP conditions were then calculated to estimate the effect of the high pressure on the permeability of tissue in different depths. We further photographed the histological sections of the TM and compared the in situ images. The following results were obtained in the control condition, where the region of depth was less than 55 μm with crossed branching beams and large pores in the superficial TM. The deeper meshwork is a silk-like tissue with abundant fluorescence separating the small size of pores. The total thickness of pathway tissues composed of TM and juxtacanalicular (JCT) is more than 100 μm. After putting a high pressure on the inner wall of the eye, the TM region progressively collapses and decreases to be less than 40 μm. Fibers of the TM became dense, and the porosity at 34 μm in the high IOP condition is comparable to that at 105 μm in the control condition. As a consequent result, the permeability of the superficial TM decreases rapidly from 120 μm2 to 49.6 μm2 and that of deeper TM decreases from 1.66 μm2 to 0.57 μm2. Heterogeneity reflected by descent in permeability reduces from 12.4 μm of the control condition to 3.74 μm of the high IOP condition. The persistently high IOP makes the TM region collapse from its normal state, in which the collagen fibers of the TM are arranged in regular to maintain the physiological permeability of the outflow pathway. In the scope of pathologically high IOP, the microstructure of the TM is sensitive to pressure and hydraulic permeability can be significantly affected by IOP. Project supported by the National Natural Science Foundation of China (Grant Nos. 31070840, 10802053, and 81201123), the Natural Science Foundation of Beijing, China (Grant No. 3122010), the Natural Science Foundation of Guangdong Province, China (Grant No. S2012040006576), the Shenzhen Science and Technology Innovation Committee, China (Grant No. KQCX20120816155352228), and the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, China (Grant No. PHR201110506).

Hot air injection for removal of dense, non-aqueous-phase liquid contaminants from low-permeability soils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Payne, F.C.

1996-08-01

The performance of soil vapor extraction systems for the recovery of volatile and semi-volatile organic compounds is potentially enhanced by the injection of heated air to increase soil temperatures. The soil temperature increase is expected to improve soil vapor extraction (SVE) performance by increasing target compound vapor pressures and by increasing soil permeability through drying. The vapor pressure increase due to temperature rise relieves the vapor pressure limit on the feasibility of soil vapor extraction. However, the system still requires an air flow through the soil system to deliver heat and to recover mobilized contaminants. Although the soil permeability canmore » be increased through drying, very low permeability soils and low permeability soils adjacent to high permeability air flow pathways will be treated slowly, if at all. AR thermal enhancement methods face this limitation. Heated air injection offers advantages relative to other thermal techniques, including low capital and operation costs. Heated air injection is at a disadvantage relative to other thermal techniques due to the low heat capacity of air. To be effective, heated air injection requires that higher air flows be established than for steam injection or radio frequency heating. Heated air injection is not economically feasible for the stratified soil system developed as a standard test for this document. This is due to the inability to restrict heated air flow to the clay stratum when a low-resistance air flow pathway is available in the adjoining sand. However, the technology should be especially attractive, both technically and economically, for low-volatile contaminant recovery from relatively homogeneous soil formations. 16 refs., 2 tabs.« less

Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.

PubMed

Stewart, E A; Saker, S; Amoaku, W M

2016-10-01

Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soltanian, Mohamad Reza; Amooie, Mohammad Amin; Cole, David R.

In this study, a field-scale carbon dioxide (CO 2) injection pilot project was conducted as part of the Southeast Regional Sequestration Partnership (SECARB) at Cranfield, Mississippi. We present higher-order finite element simulations of the compositional two-phase CO 2-brine flow and transport during the experiment. High- resolution static models of the formation geology in the Detailed Area Study (DAS) located below the oil- water contact (brine saturated) are used to capture the impact of connected flow paths on breakthrough times in two observation wells. Phase behavior is described by the cubic-plus-association (CPA) equation of state, which takes into account the polarmore » nature of water molecules. Parameter studies are performed to investigate the importance of Fickian diffusion, permeability heterogeneity, relative permeabilities, and capillarity. Simulation results for the pressure response in the injection well and the CO 2 breakthrough times at the observation wells show good agreement with the field data. For the high injection rates and short duration of the experiment, diffusion is relatively unimportant (high P clet numbers), while relative permeabilities have a profound impact on the pressure response. High-permeability pathways, created by fluvial deposits, strongly affect the CO 2 transport and highlight the importance of properly characterizing the formation heterogeneity in future carbon sequestration projects.« less

Diabetes-Induced Superoxide Anion and Breakdown of the Blood-Retinal Barrier: Role of the VEGF/uPAR Pathway

PubMed Central

El-Remessy, Azza B.; Franklin, Telina; Ghaley, Nagla; Yang, Jinling; Brands, Michael W.; Caldwell, Ruth B.; Behzadian, Mohamed Ali

2013-01-01

Diabetes-induced breakdown of the blood-retinal barrier (BRB) has been linked to hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and is likely mediated by an increase in oxidative stress. We have shown that VEGF increases permeability of retinal endothelial cells (REC) by inducing expression of urokinase plasminogen activator receptor (uPAR). The purpose of this study was to define the role of superoxide anion in VEGF/uPAR expression and BRB breakdown in diabetes. Studies were performed in streptozotocin diabetic rats and mice and high glucose (HG) treated REC. The superoxide dismutase (SOD) mimetic tempol blocked diabetes-induced permeability and uPAR expression in rats and the cell permeable SOD inhibited HG-induced expression of uPAR and VEGF in REC. Inhibiting VEGFR blocked HG-induced expression of VEGF and uPAR and GSK-3β phosphorylation in REC. HG caused β-catenin translocation from the plasma membrane into the cytosol and nucleus. Treatment with HG-conditioned media increased REC paracellular permeability that was blocked by anti-uPA or anti-uPAR antibodies. Moreover, deletion of uPAR blocked diabetes-induced BRB breakdown and activation of MMP-9 in mice. Together, these data indicate that diabetes-induced oxidative stress triggers BRB breakdown by a mechanism involving uPAR expression through VEGF-induced activation of the GSK3β/β-catenin signaling pathway. PMID:23951261

The influence of pore textures on the permeability of volcanic rocks

NASA Astrophysics Data System (ADS)

Mueller, S.; Spieler, O.; Scheu, B.; Dingwell, D.

2006-12-01

The permeability of a porous medium is strongly dependent on its porosity, as a higher proportion of pore volume is generally expected to lead to a greater probability of pore interconnectedness and the formation of a fluid-flow providing pathway. However, the relationship between permeability and porosity is not a unique one, as many other textural parameters may play an important role and substantially affect gas flow properties. Among these parameters are (a) the connection geometry (i.e. intergranular pore spaces in clastic sediments vs. bubble interconnections), (b) the pore sizes, (c) pore shape and (d) pore size distribution. The gas permeability of volcanic rocks may influence various eruptive processes. The transition from a quiescent degassing dome to rock failure (fragmentation) may, for example, be controlled by the rock's permeability, in as much as it affects the speed by which a gas overpressure in vesicles is reduced in response to decompression. It is therefore essential to understand and quantify influences of different pore textures on the degassing properties of volcanic rocks, as well as investigate the effects of permeability on eruptive processes. Using a modified shock-tube-based fragmentation apparatus, we have measured unsteady-state permeability at a high initial pressure differential. Following sudden decompression above the rock cylinder, pressurized gas flows through the sample in a steel autoclave. A transient 1D filtration code has been developed to calculate permeability using the experimental pressure decay curve within a defined volume below the sample. An external furnace around the autoclave and the use of compressed salt as sealant allows also measurements at high temperatures up to 800 °C. Over 130 permeability measurements have been performed on samples of different volcanic settings, covering a wide range of porosity. The results show a general positive relationship between porosity and permeability with a high data scatter. Analysis of the samples eruptive origin as well as the pore sizes, shapes and size distribution allow an estimation of the contribution of various textural effects to the overall permeability.

Permeability Variations Associated With Fault Reactivation in a Claystone Formation Investigated by Field Experiments and Numerical Simulations

NASA Astrophysics Data System (ADS)

Jeanne, Pierre; Guglielmi, Yves; Rutqvist, Jonny; Nussbaum, Christophe; Birkholzer, Jens

2018-02-01

We studied the relation between rupture and changes in permeability within a fault zone intersecting the Opalinus Clay formation at 300 m depth in the Mont Terri Underground Research Laboratory (Switzerland). A series of water injection experiments were performed in a borehole straddle interval set within the damage zone of the main fault. A three-component displacement sensor allowed an estimation of the displacement of a minor fault plane reactivated during a succession of step rate pressure tests. The experiment reveals that the fault hydromechanical (HM) behavior is different from one test to the other with varying pressure levels needed to trigger rupture and different slip behavior under similar pressure conditions. Numerical simulations were performed to better understand the reason for such different behavior and to investigate the relation between rupture nucleation, permeability change, pressure diffusion, and rupture propagation. Our main findings are as follows: (i) a rate frictional law and a rate-and-state permeability law can reproduce the first test, but it appears that the rate constitutive parameters must be pressure dependent to reproduce the complex HM behavior observed during the successive injection tests; (ii) almost similar ruptures can create or destroy the fluid diffusion pathways; (iii) a too high or too low diffusivity created by the main rupture prevents secondary rupture events from occurring whereas "intermediate" diffusivity favors the nucleation of a secondary rupture associated with the fluid diffusion. However, because rupture may in certain cases destroy permeability, this succession of ruptures may not necessarily create a continuous hydraulic pathway.

Simulating the Cranfield geological carbon sequestration project with high-resolution static models and an accurate equation of state

DOE PAGES

Soltanian, Mohamad Reza; Amooie, Mohammad Amin; Cole, David R.; ...

2016-10-11

In this study, a field-scale carbon dioxide (CO 2) injection pilot project was conducted as part of the Southeast Regional Sequestration Partnership (SECARB) at Cranfield, Mississippi. We present higher-order finite element simulations of the compositional two-phase CO 2-brine flow and transport during the experiment. High- resolution static models of the formation geology in the Detailed Area Study (DAS) located below the oil- water contact (brine saturated) are used to capture the impact of connected flow paths on breakthrough times in two observation wells. Phase behavior is described by the cubic-plus-association (CPA) equation of state, which takes into account the polarmore » nature of water molecules. Parameter studies are performed to investigate the importance of Fickian diffusion, permeability heterogeneity, relative permeabilities, and capillarity. Simulation results for the pressure response in the injection well and the CO 2 breakthrough times at the observation wells show good agreement with the field data. For the high injection rates and short duration of the experiment, diffusion is relatively unimportant (high P clet numbers), while relative permeabilities have a profound impact on the pressure response. High-permeability pathways, created by fluvial deposits, strongly affect the CO 2 transport and highlight the importance of properly characterizing the formation heterogeneity in future carbon sequestration projects.« less

Numerical simulation of the environmental impact of hydraulic fracturing of tight/shale gas reservoirs on near-surface groundwater: Background, base cases, shallow reservoirs, short-term gas, and water transport

PubMed Central

Reagan, Matthew T; Moridis, George J; Keen, Noel D; Johnson, Jeffrey N

2015-01-01

Hydrocarbon production from unconventional resources and the use of reservoir stimulation techniques, such as hydraulic fracturing, has grown explosively over the last decade. However, concerns have arisen that reservoir stimulation creates significant environmental threats through the creation of permeable pathways connecting the stimulated reservoir with shallower freshwater aquifers, thus resulting in the contamination of potable groundwater by escaping hydrocarbons or other reservoir fluids. This study investigates, by numerical simulation, gas and water transport between a shallow tight-gas reservoir and a shallower overlying freshwater aquifer following hydraulic fracturing operations, if such a connecting pathway has been created. We focus on two general failure scenarios: (1) communication between the reservoir and aquifer via a connecting fracture or fault and (2) communication via a deteriorated, preexisting nearby well. We conclude that the key factors driving short-term transport of gas include high permeability for the connecting pathway and the overall volume of the connecting feature. Production from the reservoir is likely to mitigate release through reduction of available free gas and lowering of reservoir pressure, and not producing may increase the potential for release. We also find that hydrostatic tight-gas reservoirs are unlikely to act as a continuing source of migrating gas, as gas contained within the newly formed hydraulic fracture is the primary source for potential contamination. Such incidents of gas escape are likely to be limited in duration and scope for hydrostatic reservoirs. Reliable field and laboratory data must be acquired to constrain the factors and determine the likelihood of these outcomes. Key Points: Short-term leakage fractured reservoirs requires high-permeability pathways Production strategy affects the likelihood and magnitude of gas release Gas release is likely short-term, without additional driving forces PMID:26726274

Discrete Fracture Network Characterization of Fractured Shale Reservoirs with Implications to Hydraulic Fracturing Optimization

NASA Astrophysics Data System (ADS)

Jin, G.

2016-12-01

Shales are important petroleum source rocks and reservoir seals. Recent developments in hydraulic fracturing technology have facilitated high gas production rates from shale and have had a strong impact on the U.S. gas supply and markets. Modeling of effective permeability for fractured shale reservoirs has been challenging because the presence of a fracture network significantly alters the reservoir hydrologic properties. Due to the frequent occurrence of fracture networks, it is of vital importance to characterize fracture networks and to investigate how these networks can be used to optimize the hydraulic fracturing. We have conducted basic research on 3-D fracture permeability characterization and compartmentization analyses for fractured shale formations, which takes the advantages of the discrete fracture networks (DFN). The DFN modeling is a stochastic modeling approach using the probabilistic density functions of fractures. Three common scenarios of DFN models have been studied for fracture permeability mapping using our previously proposed techniques. In DFN models with moderately to highly concentrated fractures, there exists a representative element volume (REV) for fracture permeability characterization, which indicates that the fractured reservoirs can be treated as anisotropic homogeneous media. Hydraulic fracturing will be most effective if the orientation of the hydraulic fracture is perpendicular to the mean direction of the fractures. A DFN model with randomized fracture orientations, on the other hand, lacks an REV for fracture characterization. Therefore, a fracture permeability tensor has to be computed from each element. Modeling of fracture interconnectivity indicates that there exists no preferred direction for hydraulic fracturing to be most effective oweing to the interconnected pathways of the fracture network. 3-D fracture permeability mapping has been applied to the Devonian Chattanooga Shale in Alabama and the results suggest that an REV exist for fluid flow and transport modeling at element sizes larger than 200 m. Fracture pathway analysis indicates that hydraulic fracturing can be equally effective for hydrocarbon fluid/gas exploration as long as its orientation is not aligned with that of the regional system fractures.

The Effect of Initial Irrigation Conditions on Heap Leaching Efficiency

NASA Astrophysics Data System (ADS)

Briseño Arellano, A. D.; Milczarek, M.; Yao, M.; Brusseau, M. L. L.

2017-12-01

Heap leaching is an unsaturated flow metal recovery process, in which mined ore is irrigated with a lixiviant to dissolve metal contained in the ore. The metal is then extracted from solution. Large scale operations involve stacking ore to depths of 6 to 18 meters on pads that may be hundreds of hectares in area. Heterogeneities within the stacked ore can lead to uneven wetting and the formation of preferential flow pathways, which reduces solution contact and lowers metal recovery. Furthermore, mineral dissolution can cause alteration of the porous media structure and loss of ore permeability. Many mine operators believe that slow initial irrigation rates help minimize permeability loss and increase metal recovery rates. However, this phenomenon has not been studied in detail. Experiments were conducted to investigate the effect of varying initial irrigation rates on leach ore stability. These were conducted with large columns (1.5 m high, 0.5 m in diameter) packed with crushed ore samples that are known to have permeability constraints. The columns were highly instrumented to assess potential changes in material properties both spatially and temporally. Water content was measured with three different methods: capacitance soil moisture sensors placed at 20-cm intervals; a neutron probe to periodically log every 30 cm from four different directions; and electrical resistivity sensors to create a 2-dimensional tomography profile of water content over time. Tensiometers were paired with the soil moisture sensors to measure matric suction and characterize moisture retention characteristics. A non-reactive tracer was used to characterize advective-dispersive transport under unsaturated conditions. A dye solution was introduced at the end of each experiment to map preferential pathways. Continuous monitoring of settling at the surface assisted in measuring consolidation and loss in permeability.

Gradual changes in permeability of inner mitochondrial membrane precede the mitochondrial permeability transition.

PubMed

Balakirev, M Y; Zimmer, G

1998-08-01

Some compounds are known to induce solute-nonselective permeability of the inner mitochondrial membrane (IMM) in Ca2+-loaded mitochondria. Existing data suggest that this process, following the opening of a mitochondrial permeability transition pore, is preceded by different solute-selective permeable states of IMM. At pH 7, for instance, the K0.5 for Ca2+-induced pore opening is 16 microM, a value 80-fold above a therapeutically relevant shift of intracellular Ca2+ during ischemia in vivo. The present work shows that in the absence of Ca2+, phenylarsine oxide and tetraalkyl thiuram disulfides (TDs) are able to induce a complex sequence of IMM permeability changes. At first, these agents activated an electrogenic K+ influx into the mitochondria. This K+-specific pathway had K0.5 = 35 mM for K+ and was inhibited by bromsulfalein with Ki = 2.5 microM. The inhibitors of mitochondrial KATP channel, ATP and glibenclamide, did not inhibit K+ transport via this pathway. Moreover, 50 microM glibenclamide induced by itself K+ influx into the mitochondria. After the increase in K+ permeability of IMM, mitochondria become increasingly permeable to protons. Mechanisms of H+ leak and nonselective permeability increase could also be different depending on the type of mitochondrial permeability transition (MPT) inducer. Thus, permeabilization of mitochondria induced by phenylarsine oxide was fully prevented by ADP and/or cyclosporin A, whereas TD-induced membrane alterations were insensitive toward these inhibitors. It is suggested that MPT in vivo leading to irreversible apoptosis is irrelevant in reversible ischemia/reperfusion injury. Copyright 1998 Academic Press.

Metabolic pathways and pharmacokinetics of natural medicines with low permeability.

PubMed

Zeng, Mei; Yang, Lan; He, Dan; Li, Yao; Shi, Mingxin; Zhang, Jingqing

2017-11-01

Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine. This review was performed using a systematic search of all available literature. It provides an overview and discussion of metabolic pathways and the pharmacokinetics of natural medicines with low permeability. The related enzymes and factors affecting them are analyzed. The series of metabolic reactions, including phase I reactions(oxidation hydrolysis, and reduction reactions) and phase II reactions (binding reactions), catalyzed by intracellular metabolic enzymes (such as CYP450, esterase, SULT, and UGT enzymes) in tissues (such as liver and gastro-intestinal tract) or in the body fluid environment were examined. The administration route, drug dose, and delivery system had a large influence on absorption, metabolism, and pharmacokinetics. Natural medicines with low permeability had distinctive metabolisms and pharmacokinetics. The metabolic and in vivo kinetic properties were favorably modified by choosing suitable drug delivery systems, administration routes and drug doses, among other variables. This study provides valuable information for clinicians and pharmacists to guide patients safe, effective, and rational drug use. The research of metabolism and pharmacokinetics is significant in guiding personalized clinical medicine.

Endophilin-1 regulates blood-brain barrier permeability via EGFR-JNK signaling pathway.

PubMed

Chen, Lin; Liu, Wenjing; Wang, Ping; Xue, Yixue; Su, Qingjie; Zeng, Chaosheng; Shang, Xiuli

2015-05-05

Endophilin-1 (Endo1), a multifunctional protein, is essential for synaptic vesicle endocytosis. However, the role and mechanism of endophilin-1 in blood-brain barrier (BBB) function are still unclear. This study was performed to determine whether endophilin-1 regulated BBB permeability via the EGFR-JNK signaling pathway. In the present study, we found that endophilin-1 over-expression in human cerebral microvascular endothelial cell (hCMEC/D3) increased BBB permeability and meanwhile reduced the expression levels of epidermal growth factor receptor (EGFR), phosphorylated c-Jun N-terminal kinase (p-JNK). While endophilin-1 knockdown led to the contrary results. After JNK inhibitor SP600125 was administered to the endophilin-1 silenced hCMEC/D3 cells, the transendothelial electrical resistance (TEER) value was decreased and the permeability coefficient values to 4kDa and 40kDa FITC-dextran were increased. Results observed by Transmission electron microscopy (TEM) showed that tight junctions (TJs) were opened. Moreover, immunofluorescence and Western blot assays revealed the discontinuous distribution of TJ-associated proteins ZO-1, occludin on cell-cell boundaries and a significant decrease in protein expressing levels. Therefore, these results indicated that endophilin-1 positively regulated BBB permeability via the EGFR-JNK signaling pathway in hCMEC/D3 cells, which would provide an experimental basis for further research on endophilin-1 mediated the opening of BBB. Copyright © 2015 Elsevier B.V. All rights reserved.

Electromagnetic-pulse-induced activation of p38 MAPK pathway and disruption of blood-retinal barrier.

PubMed

Li, Hai-Juan; Guo, Liang-Mei; Yang, Long-Long; Zhou, Yong-Chun; Zhang, Yan-Jun; Guo, Juan; Xie, Xue-Jun; Guo, Guo-Zhen

2013-06-20

The blood-retinal barrier (BRB) is critical for maintaining retina homeostasis and low permeability. In this study, we evaluated the effects of electromagnetic pulse (EMP) exposure on the permeability of BRB, alterations of tight junction (TJ) proteins of BRB and if any, involvement of mitogen-activated protein kinase (MAPK) pathway. Male Sprague-Dawley (SD) rats and RF/6A cells which were pretreated with or without MAPKs inhibitors were sham exposed or exposed to EMP at 200kV/m for 200 pulses. The alteration of BRB permeability was examined through fluorescence microscope and quantitatively assessed using Evans blue (EB) and endogenous albumin as tracers. The expressions of TJ proteins and some signaling molecules of MAPK pathway were measured by Western blots. The observations were that EMP exposure resulted in increased BRB permeability concurrent with the decreased expressions of occludin and claudin-5, which were correlated with the increased expressions of phospho-p38, phospho-JNK and phospho-ERK and could be blocked when pretreated with p38 MAPK inhibitor. Thus, the results suggested that the alterations of occludin and claudin-5 may play an important role in the disruption of TJs, which may lead to the transient breakdown of BRB after EMP exposure with the involvement of p38 MAPK pathway through phosphorylation of signaling molecules. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Assessing temporal variations in connectivity through suspended sediment hysteresis analysis

NASA Astrophysics Data System (ADS)

Sherriff, Sophie; Rowan, John; Fenton, Owen; Jordan, Phil; Melland, Alice; Mellander, Per-Erik; hUallacháin, Daire Ó.

2016-04-01

Connectivity provides a valuable concept for understanding catchment-scale sediment dynamics. In intensive agricultural catchments, land management through tillage, high livestock densities and extensive land drainage practices significantly change hydromorphological behaviour and alter sediment supply and downstream delivery. Analysis of suspended sediment-discharge hysteresis has offered insights into sediment dynamics but typically on a limited selection of events. Greater availability of continuous high-resolution discharge and turbidity data and qualitative hysteresis metrics enables assessment of sediment dynamics during more events and over time. This paper assesses the utility of this approach to explore seasonal variations in connectivity. Data were collected from three small (c. 10 km2) intensive agricultural catchments in Ireland with contrasting morphologies, soil types, land use patterns and management practices, and are broadly defined as low-permeability supporting grassland, moderate-permeability supporting arable and high-permeability supporting arable. Suspended sediment concentration (using calibrated turbidity measurements) and discharge data were collected at 10-min resolution from each catchment outlet and precipitation data were collected from a weather station within each catchment. Event databases (67-90 events per catchment) collated information on sediment export metrics, hysteresis category (e.g., clockwise, anti-clockwise, no hysteresis), numeric hysteresis index, and potential hydro-meteorological controls on sediment transport including precipitation amount, duration, intensity, stream flow and antecedent soil moisture and rainfall. Statistical analysis of potential controls on sediment export was undertaken using Pearson's correlation coefficient on separate hysteresis categories in each catchment. Sediment hysteresis fluctuations through time were subsequently assessed using the hysteresis index. Results showed the numeric hysteresis index varied over time in all three catchments. The exact response was catchment specific reflecting changing sediment availability and connectivity through time as indicated by dominant controls. In the low-permeability grassland catchment, proximal sources dominated which was consistent with observations of active channel bank erosion. Seasonal increases in rainfall increased the erosion potential but continuous grassland cover mitigated against hillslope sediment contributions despite high hydrological connectivity and surface pathways. The moderate-permeability arable catchment was dominated by events with a distal source component but those with both proximal and distal sediment sources yielded the highest sediment quantities. These events were driven by rainfall parameters suggesting sediment were surface derived and the hillslope was hydrologically connected during most events. Through time, a sustained period of rainfall increased the magnitude of negative hysteresis, likely demonstrating increasing surface hydrological connectivity due to increased groundwater saturation. Where increased hydrological connectivity coincided with low groundcover, the largest sediment exports were recorded. Events in the high permeability catchment indicated predominantly proximal sediments despite abundant distal sources from tilled fields. The infiltration dominated high permeability soils hydrologically disconnected these field sources and limited sediment supply. However, the greatest sediment export occurred in this catchment suggesting thresholds existed, which when exceeded during higher magnitude events, resulted in efficient conveyance of sediments. Hysteresis analysis offers wider utility as a tool to understand sediment pathways and connectivity issues with applications to catchment management strategies.

Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway.

PubMed

Gu, Yan-ting; Xue, Yi-xue; Wang, Yan-feng; Wang, Jin-hui; Chen, Xia; ShangGuan, Qian-ru; Lian, Yan; Zhong, Lei; Meng, Ying-nan

2013-12-01

Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator, minoxidil sulfate (MS), can selectively increase the permeability of the blood-tumor barrier (BTB); however, the mechanism by which this occurs is still under investigation. Using a rat brain glioma (C6) model, we first examined the expression levels of occludin and claudin-5 at different time points after intracarotid infusion of MS (30 μg/kg/min) by western blotting. Compared to MS treatment for 0 min group, the protein expression levels of occludin and claudin-5 in brain tumor tissue of rats showed no changes within 1 h and began to decrease significantly after 2 h of MS infusion. Based on these findings, we then used an in vitro BTB model and selective inhibitors of diverse signaling pathways to investigate whether reactive oxygen species (ROS)/RhoA/PI3K/PKB pathway play a key role in the process of the increase of BTB permeability induced by MS. The inhibitor of ROS or RhoA or PI3K or PKB significantly attenuated the expression of tight junction (TJ) protein and the increase of the BTB permeability after 2 h of MS treatment. In addition, the significant increases in RhoA activity and PKB phosphorylation after MS administration were observed, which were partly inhibited by N-2-mercaptopropionyl glycine (MPG) or C3 exoenzyme or LY294002 pretreatment. The present study indicates that the activation of signaling cascades involving ROS/RhoA/PI3K/PKB in BTB was required for the increase of BTB permeability induced by MS. Taken together, all of these results suggested that MS might increase BTB permeability in a time-dependent manner by down-regulating TJ protein expression and this effect could be related to ROS/RhoA/PI3K/PKB signal pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tea polyphenols alleviate high fat and high glucose-induced endothelial hyperpermeability by attenuating ROS production via NADPH oxidase pathway.

PubMed

Zuo, Xuezhi; Tian, Chong; Zhao, Nana; Ren, Weiye; Meng, Yi; Jin, Xin; Zhang, Ying; Ding, Shibin; Ying, Chenjiang; Ye, Xiaolei

2014-03-02

Hyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The objective of this study is to investigate the effects of green tea polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide adenine dinucleotide phosphate (NADPH) pathway. Male Wistar rats fed on a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 μg/mL) for 24 hours in vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were measured by Evans blue injection method and efflux of fluorescein isothiocyanate (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2', 7'-dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein levels of NADPH oxidase subunits were determined by Western-blot. HF diet-fed increased the endothelial permeability and ROS levels in rat aorta while HG treatments increased the endothelial permeability and ROS levels in cultured BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro. In in vitro studies, GTPs treatments protected against the HG-induced over-expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG. GTPs could alleviate endothelial hyperpermeabilities in HF diet-fed rat aorta and in HG treated BAECs. The decrease of ROS production resulting from down-regulation of NADPH oxidase contributed to the alleviation of endothelial hyperpermeability.

Identification of the dominant runoff pathways from data-based mechanistic modelling of nested catchments in temperate UK

NASA Astrophysics Data System (ADS)

Ockenden, M. C.; Chappell, N. A.

2011-05-01

SummaryUnderstanding hydrological flow pathways is important for modelling stream response, in order to address a range of environmental problems such as flood prediction, prediction of chemical loads and identification of contaminant pathways for subsequent remediation. This paper describes the use of parametrically efficient, low order models to identify the dominant modes of stream response for catchments within the Upper Eden, UK. A first order linear model adequately identified the dominant mode in all but one of the sub-catchments. A consistent pattern of time constants and pure time delays between catchments was observed over different periods of data. In the nested catchments, time constants increased as the catchment size increased from 1.1 km 2 at Gais Gill (2-7 h) to 69.4 km 2 at Kirkby Stephen (5-10 h) to 223.4 km 2 at Great Musgrave (7-16 h) to 616.4 km 2 at Temple Sowerby (11-22 h), but Blind Beck (a small catchment 8.8 km 2, time constants 11-21 h) had time constants most similar to Temple Sowerby. This was attributed to a combination of the storage role of permeable rock strata, where present, and the effect of scale on sub-surface and channel routing. A first order model could not be identified for the 1.0 km 2 Low Hall catchment, which comprises permeable sandstone overlain by Quaternary sediments. A second-order model of Low Hall stream showed a higher proportion of water taking a slower pathway (76% via a slow pathway; time constant 252 h) than a model with the same structure for the 8.8 km 2 Blind Beck (46% via slow pathway; time constant 60 h), where only 38% of the basin was underlain by the same permeable sandstone. This highlights the need to quantify the role of deep pathways through permeable rock, where present, in addition to the effect of catchment size on response times.

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

PubMed

Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

2016-05-23

DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Permeability Evolution With Shearing of Simulated Faults in Unconventional Shale Reservoirs

NASA Astrophysics Data System (ADS)

Wu, W.; Gensterblum, Y.; Reece, J. S.; Zoback, M. D.

2016-12-01

Horizontal drilling and multi-stage hydraulic fracturing can lead to fault reactivation, a process thought to influence production from extremely low-permeability unconventional reservoir. A fundamental understanding of permeability changes with shear could be helpful for optimizing reservoir stimulation strategies. We examined the effects of confining pressure and frictional sliding on fault permeability in Eagle Ford shale samples. We performed shear-flow experiments in a triaxial apparatus on four shale samples: (1) clay-rich sample with sawcut fault, (2) calcite-rich sample with sawcut fault, (3) clay-rich sample with natural fault, and (4) calcite-rich sample with natural fault. We used pressure pulse-decay and steady-state flow techniques to measure fault permeability. Initial pore and confining pressures are set to 2.5 MPa and 5.0 MPa, respectively. To investigate the influence of confining pressure on fault permeability, we incrementally raised and lowered the confining pressure and measure permeability at different effective stresses. To examine the effect of frictional sliding on fault permeability, we slide the samples four times at a constant shear displacement rate of 0.043 mm/min for 10 minutes each and measure fault permeability before and after frictional sliding. We used a 3D Laser Scanner to image fault surface topography before and after the experiment. Our results show that frictional sliding can enhance fault permeability at low confining pressures (e.g., ≥5.0 MPa) and reduce fault permeability at high confining pressures (e.g., ≥7.5 MPa). The permeability of sawcut faults almost fully recovers when confining pressure returns to the initial value, and increases with sliding due to asperity damage and subsequent dilation at low confining pressures. In contrast, the permeability of natural faults does not fully recover. It initially increases with sliding, but then decreases with further sliding most likely due to fault gouge blocking fluid pathways.

Variation of brine compositions resulting from flow from matrix or fracture permeability, investigated by high pressure laboratory experiments

NASA Astrophysics Data System (ADS)

Poszwa, A. C.; Coleman, M. L.; Pouya, A.; Ader, M.; Bounenni, A.

2003-04-01

Planning oil production from a chalk reservoir oilfield is difficult because the matrix usually has low permeability despite its high porosity. Most oil is thought to come from fracture porosity but the matrix contribution should increase as compaction occurs during production. To better understand the respective contributions from matrix and fracture, we studied the geochemical characteristics of fluids using high-pressure brine flow experiments on chalk cores. During the experiment axial load was changed relative to confining pressure to induce fractures and to close them again. We used chlorine stable isotope variations to study fluid pathway, because chlorine is a chemically conservative element in sedimentary systems and its isotopes fractionate only with physical processes like diffusion or adsorption that could occur mainly in the chalk matrix. A first experiment was performed on a very porous chalk from Henley (on-shore UK) and using a low-salinity brine. Large variations of brine Cl isotope composition were observed (from -0.56 to +0.08 per mil). The variations were correlated positively with the brine flux through the chalk and the permeability of the rock, both parameters controlled by the rock fracturing. A second experiment used brine with salinity similar to that of seawater. In this case, chemical and isotopic variations were not significant. From the beginning, the chalk structure seems to have been destroyed very quickly (induced fracture porosity collapsed) possibly because of the fluid nature, so that whatever pressure was applied, the permeability did not change significantly. Using Valhall reservoir chalk (offshore Norwegian North Sea) and fluid half the salinity of seawater in a third experiment, we obtained a large range of permeabilities. Brine isotopic trends were very similar on average to those of the first experiment even though variations were smaller (Cl isotopes from -0.09 to +0.29 per mil) and not significantly correlated simply to permeability values. The highest isotopic values were in brine flowed through chalk when the permeability was high and fractures opened; the lowest values were in brine flowed through the chalk when its permeability was reduced by closing fractures and increasing the relative contribution from matrix flow where diffusion processes fractionated chlorine isotopes. From this work it seems that the relative contributions from fracture and matrix permeability in reservoirs can be estimated from the geochemical compositions of brines that flowed from them.

Activation of the TXNIP/NLRP3 inflammasome pathway contributes to inflammation in diabetic retinopathy: a novel inhibitory effect of minocycline.

PubMed

Chen, Wei; Zhao, Minjie; Zhao, Shuzhi; Lu, Qianyi; Ni, Lisha; Zou, Chen; Lu, Li; Xu, Xun; Guan, Huaijin; Zheng, Zhi; Qiu, Qinghua

2017-02-01

Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR. Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference. In high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1β and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS-TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis. Together, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.

Time-dependent permeability evolution in compacting volcanic fracture systems and implications for gas overpressure

NASA Astrophysics Data System (ADS)

Farquharson, Jamie I.; Wadsworth, Fabian B.; Heap, Michael J.; Baud, Patrick

2017-06-01

Volcanic eruptions are driven by the ascent of volatile-laden magma. The capacity of a volcano system to outgas these volatiles-its permeability-controls the explosive potential, and fractures at volcanic conduit margins play a crucial role in tempering eruption explosivity by acting as outgassing pathways. However, these fractures are often filled with hot volcanic debris that welds and compacts over time, meaning that these permeable pathways have a finite lifetime. While numerous studies emphasize that permeability evolution is important for regulating pressure in shallow volcanic systems, how and when this occurs remains an outstanding question in volcanology. In this contribution, we show that different pressure evolution regimes can be expected across a range of silicic systems as a function of the width and distribution of fractures in the system, the timescales over which they can outgas (a function of depth and temperature), and the permeability of the host material. We define outgassing, diffusive relaxation, and pressure increase regimes, which are distinguished by comparing the characteristic timescales over which they operate. Moreover, we define a critical permeability threshold, which determines (in concert with characteristic timescales of diffusive mass exchange between the pore and melt phases) whether systems fracture and outgas efficiently, or if a volcano will be prone to pressure increases, incomplete healing, and explosive failure.

The effect of pore-scale geometry and wettability on two-phase relative permeabilities within elementary cells

NASA Astrophysics Data System (ADS)

Bianchi Janetti, Emanuela; Riva, Monica; Guadagnini, Alberto

2017-04-01

We study the relative role of the complex pore space geometry and wettability of the solid matrix on the quantification of relative permeabilities characterizing steady state immiscible two-phase flow in porous media. We do so by considering elementary cells, which are typically employed in upscaling frameworks based on, e.g., homogenization or volume averaging. In this context one typically relies on the solution of pore-scale physics at a scale which is much smaller than that of an investigated porous system. Pressure-driven two-phase flow following simultaneous co-current injection of water and oil is numerically solved for a suite of regular and stochastically generated two-dimensional explicit elementary cells with fixed porosity and sharing main topological/morphological features. We show that relative permeabilities of the randomly generated elementary cells are significantly influenced by the formation of preferential percolation paths (principal pathways), giving rise to a strongly nonuniform distribution of fluid fluxes. These pathways are a result of the spatially variable resistance that the random pore structures exert on the fluid. The overall effect on relative permeabilities of the diverse organization of principal pathways, as driven by a given random realization at the scale of the unit cell, is significantly larger than that of the wettability of the host rock. In contrast to what can be observed for the random cells analyzed, relative permeabilities of regular cells display a clear trend with contact angle at the investigated scale. Our findings suggest the need to perform systematic upscaling studies in a stochastic context, to propagate the effects of uncertain pore space geometries to a probabilistic description of relative permeability curves at the continuum scale.

Lipopolysaccharide regulation of intestinal tight junction permeability is mediated by TLR-4 signal transduction pathway activation of FAK and MyD88

PubMed Central

Guo, Shuhong; Nighot, Meghali; Al-Sadi, Rana; Alhmoud, Tarik; Nighot, Prashant; Ma, Thomas Y.

2015-01-01

Gut-derived bacterial lipopolysaccharides (LPS) play an essential role in inducing intestinal and systemic inflammatory responses and have been implicated as a pathogenic factor of necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). The defective intestinal tight junction (TJ) barrier has been shown to be an important factor contributing to the development of intestinal inflammation. LPS, at physiological concentrations, cause an increase in intestinal tight junction permeability (TJP) via a TLR-4 dependent process; however the intracellular mechanisms that mediate LPS regulation of intestinal TJP remain unclear. The aim of this study was to investigate the adaptor proteins and the signaling interactions that mediate LPS modulation of intestinal TJ barrier using an in-vitro and in-vivo model system. LPS caused a TLR-4 dependent activation of membrane-associated adaptor protein FAK in Caco-2 monolayers. LPS caused an activation of both MyD88-dependent and –independent pathways. SiRNA silencing of MyD88 prevented LPS-induced increase in TJP. LPS caused a MyD88-dependent activation of IRAK4. TLR-4, FAK and MyD88 were co-localized. SiRNA silencing of TLR-4 inhibited TLR-4 associated FAK activation; and FAK knockdown prevented MyD88 activation. In-vivo studies also confirmed that LPS-induced increase in mouse intestinal permeability was associated with FAK and MyD88 activation; knockdown of intestinal epithelial FAK prevented LPS-induced increase in intestinal permeability. Additionally, high dose LPS-induced intestinal inflammation was also dependent on TLR-4/FAK/MyD88 signal-transduction axis. Our data show for the first time that LPS-induced increase in intestinal TJP and intestinal inflammation was regulated by TLR-4 dependent activation of FAK-MyD88-IRAK4 signaling pathway. PMID:26466961

Field Test of Enhanced Remedial Amendment Delivery Using a Shear-Thinning Fluid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Truex, Michael J.; Vermeul, Vincent R.; Adamson, David

2015-03-01

Heterogeneity of hydraulic properties in aquifers may lead to contaminants residing in lower-permeability zones where it is difficult to deliver remediation amendments using conventional injection processes. The focus of this effort is to examine use of a shear-thinning fluid (STF) to improve the uniformity of remedial amendment distribution within a heterogeneous aquifer. Previous studies have demonstrated the significant potential of STFs for improving remedial amendment delivery in heterogeneous aquifers, but quantitative evaluation of these improvements from field applications are lacking. A field-scale test was conducted that compares data from successive injection of a tracer in water followed by injection ofmore » a tracer in a STF to evaluate the impact of the STF on tracer distribution uniformity in the presence of permeability contrasts within the targeted injection zone. Data from tracer breakthrough at multiple depth-discrete monitoring intervals and electrical resistivity tomography showed that inclusion of STF in the injection solution slowed movement in high-permeability pathways, improved delivery of amendment to low-permeability materials, and resulted in better uniformity in injected fluid distribution within the targeted treatment zone.« less

Biophysical Model of Ion Transport across Human Respiratory Epithelia Allows Quantification of Ion Permeabilities

PubMed Central

Garcia, Guilherme J.M.; Boucher, Richard C.; Elston, Timothy C.

2013-01-01

Lung health and normal mucus clearance depend on adequate hydration of airway surfaces. Because transepithelial osmotic gradients drive water flows, sufficient hydration of the airway surface liquid depends on a balance between ion secretion and absorption by respiratory epithelia. In vitro experiments using cultures of primary human nasal epithelia and human bronchial epithelia have established many of the biophysical processes involved in airway surface liquid homeostasis. Most experimental studies, however, have focused on the apical membrane, despite the fact that ion transport across respiratory epithelia involves both cellular and paracellular pathways. In fact, the ion permeabilities of the basolateral membrane and paracellular pathway remain largely unknown. Here we use a biophysical model for water and ion transport to quantify ion permeabilities of all pathways (apical, basolateral, paracellular) in human nasal epithelia cultures using experimental (Ussing Chamber and microelectrode) data reported in the literature. We derive analytical formulas for the steady-state short-circuit current and membrane potential, which are for polarized epithelia the equivalent of the Goldman-Hodgkin-Katz equation for single isolated cells. These relations allow parameter estimation to be performed efficiently. By providing a method to quantify all the ion permeabilities of respiratory epithelia, the model may aid us in understanding the physiology that regulates normal airway surface hydration. PMID:23442922

Sub-Seafloor Carbon Dioxide Storage Potential on the Juan de Fuca Plate, Western North America

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jerry Fairley; Robert Podgorney

2012-11-01

The Juan de Fuca plate, off the western coast of North America, has been suggested as a site for geological sequestration of waste carbon dioxide because of its many attractive characteristics (high permeability, large storage capacity, reactive rock types). Here we model CO2 injection into fractured basalts comprising the upper several hundred meters of the sub-seafloor basalt reservoir, overlain with low-permeability sediments and a large saline water column, to examine the feasibility of this reservoir for CO2 storage. Our simulations indicate that the sub-seafloor basalts of the Juan de Fuca plate may be an excellent CO2 storage candidate, as multiplemore » trapping mechanisms (hydrodynamic, density inversions, and mineralization) act to keep the CO2 isolated from terrestrial environments. Questions remain about the lateral extent and connectivity of the high permeability basalts; however, the lack of wells or boreholes and thick sediment cover maximize storage potential while minimizing potential leakage pathways. Although promising, more study is needed to determine the economic viability of this option.« less

Novel channel-mediated choline transport in cholinergic neurons of the mouse retina.

PubMed

Ishii, Toshiyuki; Homma, Kohei; Mano, Asuka; Akagi, Takumi; Shigematsu, Yasuhide; Shimoda, Yukio; Inoue, Hiroyoshi; Kakinuma, Yoshihiko; Kaneda, Makoto

2017-10-01

Choline uptake into the presynaptic terminal of cholinergic neurons is mediated by the high-affinity choline transporter and is essential for acetylcholine synthesis. In a previous study, we reported that P2X 2 purinoceptors are selectively expressed in OFF-cholinergic amacrine cells of the mouse retina. Under specific conditions, P2X 2 purinoceptors acquire permeability to large cations, such as N -methyl-d-glucamine, and therefore potentially could act as a noncanonical pathway for choline entry into neurons. We tested this hypothesis in OFF-cholinergic amacrine cells of the mouse retina. ATP-induced choline currents were observed in OFF-cholinergic amacrine cells, but not in ON-cholinergic amacrine cells, in mouse retinal slice preparations. High-affinity choline transporters are expressed at higher levels in ON-cholinergic amacrine cells than in OFF-cholinergic amacrine cells. In dissociated preparations of cholinergic amacrine cells, ATP-activated cation currents arose from permeation of extracellular choline. We also examined the pharmacological properties of choline currents. Pharmacologically, α,β-methylene ATP did not produce a cation current, whereas ATPγS and benzoyl-benzoyl-ATP (BzATP) activated choline currents. However, the amplitude of the choline current activated by BzATP was very small. The choline current activated by ATP was strongly inhibited by pyridoxalphosphate-6-azophenyl-2',4'-sulfonic acid. Accordingly, P2X 2 purinoceptors expressed in HEK-293T cells were permeable to choline and similarly functioned as a choline uptake pathway. Our physiological and pharmacological findings support the hypothesis that P2 purinoceptors, including P2X 2 purinoceptors, function as a novel choline transport pathway and may provide a new regulatory mechanism for cholinergic signaling transmission at synapses in OFF-cholinergic amacrine cells of the mouse retina. NEW & NOTEWORTHY Choline transport across the membrane is exerted by both the high-affinity and low-affinity choline transporters. We found that choline can permeate P2 purinergic receptors, including P2X 2 purinoceptors, in cholinergic neurons of the retina. Our findings show the presence of a novel choline transport pathway in cholinergic neurons. Our findings also indicate that the permeability of P2X 2 purinergic receptors to choline observed in the heterologous expression system may have a physiological relevance in vivo. Copyright © 2017 the American Physiological Society.

The generation and evolution of anisotropic gas-permeability during viscous deformation in conduit-filling ignimbrites

NASA Astrophysics Data System (ADS)

Kolzenburg, Stephan; Russell, Kelly

2015-04-01

Gas-permeability plays a governing role in the pre-explosive pressurization of volcanic edifices. Pressurization may only occur once the total volume flux of gases emitted by an underlying magmatic or hydrothermal source exceeds the flow capacity of the permeable pathways present in the edifice. We have measured the physical properties (strain, porosity, permeability and ultrasonic wave velocities) of breadcrust bombs recovered from the deposits of the 2350 B.P. eruption of Mt Meager, BC, Canada. These rocks represent a conduit-infilling pyroclastic breccia that underwent various degrees of welding and deformation and present a remarkable opportunity to constrain the nature and timescale of mechanical processes operating within explosive volcanic conduits during repose periods between eruptive cycles. Here we present data from permeability measurements along the directions of maximum and minimum shortening which help quantifying the effect of vesicle microstructure on permeability. Permeability is measured by applying a range of confining pressures (between 3.4 and 17.2 MPa) to each sample and imposing a constant head (of 0.2 to 3.5 MPa) across the sample. The permeability is then determined using a modified version of Darcy's law applicable to compressible fluids. These rocks display a profound directionality in the measured physical properties resulting from the deformation-induced fabric. For all samples the permeability across the elongation fabric is highly correlated to the sample porosity whereas along the elongation fabric there is little effect of porosity on permeability. At porosity values of about 20% the permeability seems to reach a minimum at 10-16 m2 and does not change significantly with further reduction of porosity. Further, the effect of confining pressure on the permeability of these samples appears to be more pronounced across the elongation fabric than along the elongation fabric. The deformation fabric has a significant effect on the gas-permeability of the deposit. Porosity, on the other hand, appears to play a secondary role. This, fabric dependent, anisotropic permeability evolution of fragmental deposits during welding directly affects the gas escape from, and transport through the deposit and, therewith, plays a key role in the gas-pressure distribution and evolution within the volcano.

Paranodal permeability in `myelin mutants'

PubMed Central

Shroff, S.; Mierzwa, A.; Scherer, S.S.; Peles, E.; Arevalo, J.C.; Chao, M.V.; Rosenbluth, J.

2011-01-01

Fluorescent dextran tracers of varying sizes have been used to assess paranodal permeability in myelinated sciatic nerve fibers from control and three `myelin mutant' mice, Caspr-null, cst-null and shaking. We demonstrate that in all of these the paranode is permeable to small tracers (3kDa, 10kDa), which penetrate most fibers, and to larger tracers (40kDa, 70kDa), which penetrate far fewer fibers and move shorter distances over longer periods of time. Despite gross diminution in transverse bands in the Caspr-null and cst-null mice, the permeability of their paranodal junctions is equivalent to that in controls. Thus, deficiency of transverse bands in these mutants does not increase the permeability of their paranodal junctions to the dextrans we used, moving from the perinodal space through the paranode to the internodal periaxonal space. In addition, we show that the shaking mice, which have thinner myelin and shorter paranodes, show increased permeability to the same tracers despite the presence of transverse bands. We conclude that the extent of penetration of these tracers does not depend on the presence or absence of transverse bands but does depend on the length of the paranode and, in turn, on the length of `pathway 3', the helical extracellular pathway that passes through the paranode parallel to the lateral edge of the myelin sheath. PMID:21618613

The effect of CO2-fluid-rock interactions on the porosity and permeability of calcite-bearing sandstone

NASA Astrophysics Data System (ADS)

Lamy-Chappuis, B.; Yardley, B.; Grattoni, C.

2013-12-01

Brine acidification following CO2 dissolution will initiate fluid-rock interactions that could significantly modify porosity, permeability and therefore the capacity and injectivity of a reservoir. We have investigated experimentally the dissolution of calcite in sandstone cores injected with CO2-saturated brine, and the effect this has on permeability. A series of CT (Computerized Tomography) - monitored experiments were conducted on a Jurassic sandstone (porosity = 30%, permeability = 10mD, calcite content = 5% in the form of dispersed shell fragments). Brine saturated with CO2 at pressures up to 1 MPa was injected into 5cm long, 3.75cm diameter cores at a flow rate of 1 ml/min and room temperature. The data showed quasi-instantaneous dissolution of the calcite even at low CO2 concentrations (0.15 Molar) and high fluid interstitial velocities (1mm/s), with the migration of a calcite dissolution front through the core recorded by successive CT scans. The resulting permeability increase was 60 - 80% whereas the predicted permeability change for the observed increase in porosity is only 10 - 20% using the Kozeny-Carman relationship. This result is particularly significant because the effect of porosity increase on permeability is usually modelled with this relationship, irrespective of the mechanism of porosity increase. Micro-CT scans (pixel resolution: 2.5 microns) of unreacted cores were used to generate 3D porosity models with calcite either treated as solid (pre-reaction model) or converted to pores (post-reaction model). FLUENT simulations performed using these models predicted the observed large relative changes in permeability with calcite dissolution but overestimated absolute permeability by an order of magnitude. This was probably due to the scan resolution being too coarse to correctly model pore throats. The observed large change in permeability for a small change in porosity may have resulted from increase in connectivity, focused dissolution at the pore throats or reduction in tortuosity. SEM (Scanning Electron Microscope) imaging demonstrates dissolution of relatively large isolated shell fragments but this had little effect on the overall connectivity. No calcite cement was observed at the pore throats in the unreacted specimens. The micro-CT scans indicate a modest tortuosity decrease from 2.00 to 1.85 when calcite is dissolved, but this change in tortuosity results from the opening of new flow paths as the dissolution of discrete grains opened new flow paths and created shortcuts, not from changes to the sinuosity of existing pathways. We suggest that the marked discrepancy in the effect of calcite dissolution on permeability between our experimental data and standard models arises because of the very different way in which the porosity is increased (new pathways rather than inflation). While our results cast doubt on the general applicability of standard models for porosity-permeability relationships for situations in which porosity changes by grain-specific reactions, it is encouraging that pore scale modelling is able to reproduce the experimental relationships.

Permeability Evolution of Slowly Slipping Faults in Shale Reservoirs

NASA Astrophysics Data System (ADS)

Wu, Wei; Reece, Julia S.; Gensterblum, Yves; Zoback, Mark D.

2017-11-01

Slow slip on preexisting faults during hydraulic fracturing is a process that significantly influences shale gas production in extremely low permeability "shale" (unconventional) reservoirs. We experimentally examined the impacts of mineralogy, surface roughness, and effective stress on permeability evolution of slowly slipping faults in Eagle Ford shale samples. Our results show that fault permeability decreases with slip at higher effective stress but increases with slip at lower effective stress. The permeabilities of saw cut faults fully recover after cycling effective stress from 2.5 to 17.5 to 2.5 MPa and increase with slip at constant effective stress due to asperity damage and dilation associated with slip. However, the permeabilities of natural faults only partially recover after cycling effective stress returns to 2.5 MPa and decrease with slip due to produced gouge blocking fluid flow pathways. Our results suggest that slowly slipping faults have the potential to enhance reservoir stimulation in extremely low permeability reservoirs.

Convection in horizontal decompaction channels at the base of the lithosphere

NASA Astrophysics Data System (ADS)

Schools, J.; Montesi, L.

2017-12-01

As mantle melt ascends and cools through the porous matrix of a lithosphere, it crystallizes. At some depth, the crystallization rate of the ascending melt usually reaches a point where melt pathways are clogged, and permeability is reduced to zero. This is the depth of the permeability barrier. As melt collects beneath the barrier, pressure increases, forcing open an area of high porosity beneath the permeability barrier known as the decompaction channel. Previous analyses of permeability barriers and decompaction channels were conducted for mid-ocean ridges on Earth, where the permeability barrier is sloped following the age of the lithosphere, allows melt to ascent to the ridge axis. On other planetary bodies, such as Mars and Io, a lack of plate tectonics favors sub-horizontal barriers, without an obvious direction for melt ascent. We show here that the solid-melt aggregate in the decompaction may start convecting, affecting heat transport into the overlying lithosphere and generating relief on the permeability barrier that may focus melt. Using the finite element code ASPECT, we model the formation and evolution of permeability barriers and underlying decompaction channels in two dimensions under conditions representative of a single plate planetary lithosphere. In these models permeability barriers form in less than a few thousand years and the decompaction channel forms concurrently. Once the barrier/channel is in place, downwellings appear within the channels. They seem to be linked to crystallization of the melt at the top of the channel, which increases aggregate density and results in an unstable stratification. In these models, the viscosity of the channel is low because of the porosity-dependence of viscosity, which makes convection possible. As a result of convection, melt focusing at areas of high permeability at the top of the channel. Increases heat flux in these regions slightly elevates the barrier, allowing more melt to focus at these locations. These events occur within the first 3 million years of the model run. Future models will attempt to better understand the conditions necessary for this convection to take place and what its geological consequences may be.

The role of mitosis in LDL transport through cultured endothelial cell monolayers

PubMed Central

Cancel, Limary M.

2011-01-01

We (7) have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for LDL transport under convective conditions, accounting for >90% of the transport. We (8) have also recently shown that the permeability of bovine aortic endothelial cell monolayers is highly correlated with their rate of apoptosis and that inhibiting apoptosis lowers the permeability of the monolayers to LDL. To explore the role of mitosis in the leaky junction pathway, the microtubule-stabilizing agent paclitaxel was used to alter the rate of mitosis, and LDL flux and water flux (Jv) were measured. Control monolayers had an average mitosis rate of 0.029%. Treatment with paclitaxel (2.5 μM) for 1.5, 3, 4.5, or 6 h yielded increasing rates of mitosis ranging from 0.099% to 1.03%. The convective permeability of LDL (Pe) increased up to fivefold, whereas Jv increased up to threefold, over this range of mitosis rates. We found strong correlations between the mitosis rate and both Pe and Jv. However, compared with our previous apoptosis study (8), we found that mitosis was only half as effective as apoptosis in increasing Pe. The results led us to conclude that while mitotsis-related leaky junctions might play a role in the initial infiltration of LDL into the artery wall, the progression of atherosclerosis might be more closely correlated with apoptosis-related leaky junctions. PMID:21169397

IkappaB is a sensitive target for oxidation by cell-permeable chloramines: inhibition of NF-kappaB activity by glycine chloramine through methionine oxidation.

PubMed

Midwinter, Robyn G; Cheah, Fook-Choe; Moskovitz, Jackob; Vissers, Margret C; Winterbourn, Christine C

2006-05-15

Hypochlorous acid (HOCl) is produced by the neutrophil enzyme, myeloperoxidase, and reacts with amines to generate chloramines. These oxidants react readily with thiols and methionine and can affect cell-regulatory pathways. In the present study, we have investigated the ability of HOCl, glycine chloramine (Gly-Cl) and taurine chloramine (Tau-Cl) to oxidize IkappaBalpha, the inhibitor of NF-kappaB (nuclear factor kappaB), and to prevent activation of the NF-kappaB pathway in Jurkat cells. Glycine chloramine (Gly-Cl) and HOCl were permeable to the cells as determined by oxidation of intracellular GSH and inactivation of glyceraldehyde-3-phosphate dehydrogenase, whereas Tau-Cl showed no detectable cell permeability. Both Gly-Cl (20-200 muM) and HOCl (50 microM) caused oxidation of IkappaBalpha methionine, measured by a shift in electrophoretic mobility, when added to the cells in Hanks buffer. In contrast, a high concentration of Tau-Cl (1 mM) in Hanks buffer had no effect. However, Tau-Cl in full medium did modify IkappaBalpha. This we attribute to chlorine exchange with other amines in the medium to form more permeable chloramines. Oxidation by Gly-Cl prevented IkappaBalpha degradation in cells treated with TNFalpha (tumour necrosis factor alpha) and inhibited nuclear translocation of NF-kappaB. IkappaBalpha modification was reversed by methionine sulphoxide reductase, with both A and B forms required for complete reduction. Oxidized IkappaBalpha persisted intracellularly for up to 6 h. Reversion occurred in the presence of cycloheximide, but was prevented if thioredoxin reductase was inhibited, suggesting that it was due to endogenous methionine sulphoxide reductase activity. These results show that cell-permeable chloramines, either directly or when formed in medium, could regulate NF-kappaB activation via reversible IkappaBalpha oxidation.

Biophysical model of ion transport across human respiratory epithelia allows quantification of ion permeabilities.

PubMed

Garcia, Guilherme J M; Boucher, Richard C; Elston, Timothy C

2013-02-05

Lung health and normal mucus clearance depend on adequate hydration of airway surfaces. Because transepithelial osmotic gradients drive water flows, sufficient hydration of the airway surface liquid depends on a balance between ion secretion and absorption by respiratory epithelia. In vitro experiments using cultures of primary human nasal epithelia and human bronchial epithelia have established many of the biophysical processes involved in airway surface liquid homeostasis. Most experimental studies, however, have focused on the apical membrane, despite the fact that ion transport across respiratory epithelia involves both cellular and paracellular pathways. In fact, the ion permeabilities of the basolateral membrane and paracellular pathway remain largely unknown. Here we use a biophysical model for water and ion transport to quantify ion permeabilities of all pathways (apical, basolateral, paracellular) in human nasal epithelia cultures using experimental (Ussing Chamber and microelectrode) data reported in the literature. We derive analytical formulas for the steady-state short-circuit current and membrane potential, which are for polarized epithelia the equivalent of the Goldman-Hodgkin-Katz equation for single isolated cells. These relations allow parameter estimation to be performed efficiently. By providing a method to quantify all the ion permeabilities of respiratory epithelia, the model may aid us in understanding the physiology that regulates normal airway surface hydration. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

In vitro porcine blood-brain barrier model for permeability studies: pCEL-X software pKa(FLUX) method for aqueous boundary layer correction and detailed data analysis.

PubMed

Yusof, Siti R; Avdeef, Alex; Abbott, N Joan

2014-12-18

In vitro blood-brain barrier (BBB) models from primary brain endothelial cells can closely resemble the in vivo BBB, offering valuable models to assay BBB functions and to screen potential central nervous system drugs. We have recently developed an in vitro BBB model using primary porcine brain endothelial cells. The model shows expression of tight junction proteins and high transendothelial electrical resistance, evidence for a restrictive paracellular pathway. Validation studies using small drug-like compounds demonstrated functional uptake and efflux transporters, showing the suitability of the model to assay drug permeability. However, one limitation of in vitro model permeability measurement is the presence of the aqueous boundary layer (ABL) resulting from inefficient stirring during the permeability assay. The ABL can be a rate-limiting step in permeation, particularly for lipophilic compounds, causing underestimation of the permeability. If the ABL effect is ignored, the permeability measured in vitro will not reflect the permeability in vivo. To address the issue, we explored the combination of in vitro permeability measurement using our porcine model with the pKa(FLUX) method in pCEL-X software to correct for the ABL effect and allow a detailed analysis of in vitro (transendothelial) permeability data, Papp. Published Papp using porcine models generated by our group and other groups are also analyzed. From the Papp, intrinsic transcellular permeability (P0) is derived by simultaneous refinement using a weighted nonlinear regression, taking into account permeability through the ABL, paracellular permeability and filter restrictions on permeation. The in vitro P0 derived for 22 compounds (35 measurements) showed good correlation with P0 derived from in situ brain perfusion data (r(2)=0.61). The analysis also gave evidence for carrier-mediated uptake of naloxone, propranolol and vinblastine. The combination of the in vitro porcine model and the software analysis provides a useful tool to better predict BBB permeability in vivo and gain better mechanistic information about BBB permeation. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Quantifying the impact of early calcite cementation on the reservoir quality of carbonate rocks: A 3D process-based model

NASA Astrophysics Data System (ADS)

Hosa, Aleksandra; Wood, Rachel

2017-06-01

The reservoir properties of carbonate rocks are controlled by both deposition and diagenesis. The latter includes the early precipitation of calcite cements, which can exert a strong control on the evolution of subsequent diagenetic pathways. We quantify the impact of early marine cement growth in grainstones on evolving pore space by examining trends in the relationship between cementation and permeability using a 3D process-based model (Calcite3D). The model assumes varying proportions of polycrystalline and monocrystalline grain types, upon which we grow isopachous and syntaxial calcite cement types, respectively. We model two syntaxial cement shapes, compact and elongated, that approximate the geometries of typical rhombohedral calcite forms. Results demonstrate the effect of cement competition: an increasing proportion of monocrystalline grains creates stronger competition and a reduction in the impact of individual grains on final calcite cement volume and porosity. Isopachous cement is effective in closing pore throats and limiting permeability. We also show that the impact of syntaxial cement on porosity occlusion and therefore flow is highly dependent on monocrystalline grain location and the orientation of crystal axes. This demonstrates the importance of diagenetic overprint in controlling the evolution of rock properties, but also that this process can be essentially random. We also show that diagenesis alone can create notable heterogeneity in the permeability of carbonates. While Calcite3D is successful in modelling realistic changes in cement volumes and pore space morphology, modelled permeabilities (0.01 -30D) are above the range reported in reservoir grainstones due to the very high permeability of the initial synthetic sediment deposit (58.9D). Poroperm data generated by Calcite3D, however, exhibits a linear relationship between the logarithms of porosity and permeability with a high coefficient of determination, as observed in natural media.

Metabolic Complementation in Bacterial Communities: Necessary Conditions and Optimality

PubMed Central

Mori, Matteo; Ponce-de-León, Miguel; Peretó, Juli; Montero, Francisco

2016-01-01

Bacterial communities may display metabolic complementation, in which different members of the association partially contribute to the same biosynthetic pathway. In this way, the end product of the pathway is synthesized by the community as a whole. However, the emergence and the benefits of such complementation are poorly understood. Herein, we present a simple model to analyze the metabolic interactions among bacteria, including the host in the case of endosymbiotic bacteria. The model considers two cell populations, with both cell types encoding for the same linear biosynthetic pathway. We have found that, for metabolic complementation to emerge as an optimal strategy, both product inhibition and large permeabilities are needed. In the light of these results, we then consider the patterns found in the case of tryptophan biosynthesis in the endosymbiont consortium hosted by the aphid Cinara cedri. Using in-silico computed physicochemical properties of metabolites of this and other biosynthetic pathways, we verified that the splitting point of the pathway corresponds to the most permeable intermediate. PMID:27774085

The Andes Virus Nucleocapsid Protein Directs Basal Endothelial Cell Permeability by Activating RhoA

PubMed Central

Gorbunova, Elena E.; Simons, Matthew J.; Gavrilovskaya, Irina N.

2016-01-01

ABSTRACT Andes virus (ANDV) predominantly infects microvascular endothelial cells (MECs) and nonlytically causes an acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). In HPS patients, virtually every pulmonary MEC is infected, MECs are enlarged, and infection results in vascular leakage and highly lethal pulmonary edema. We observed that MECs infected with the ANDV hantavirus or expressing the ANDV nucleocapsid (N) protein showed increased size and permeability by activating the Rheb and RhoA GTPases. Expression of ANDV N in MECs increased cell size by preventing tuberous sclerosis complex (TSC) repression of Rheb-mTOR-pS6K. N selectively bound the TSC2 N terminus (1 to 1403) within a complex containing TSC2/TSC1/TBC1D7, and endogenous TSC2 reciprocally coprecipitated N protein from ANDV-infected MECs. TSCs normally restrict RhoA-induced MEC permeability, and we found that ANDV infection or N protein expression constitutively activated RhoA. This suggests that the ANDV N protein alone is sufficient to activate signaling pathways that control MEC size and permeability. Further, RhoA small interfering RNA, dominant-negative RhoA(N19), and the RhoA/Rho kinase inhibitors fasudil and Y27632 dramatically reduced the permeability of ANDV-infected MECs by 80 to 90%. Fasudil also reduced the bradykinin-directed permeability of ANDV and Hantaan virus-infected MECs to control levels. These findings demonstrate that ANDV activation of RhoA causes MEC permeability and reveal a potential edemagenic mechanism for ANDV to constitutively inhibit the basal barrier integrity of infected MECs. The central importance of RhoA activation in MEC permeability further suggests therapeutically targeting RhoA, TSCs, and Rac1 as potential means of resolving capillary leakage during hantavirus infections. PMID:27795403

An extended model based on the modified Nernst-Planck equation for describing transdermal iontophoresis of weak electrolytes.

PubMed

Imanidis, Georgios; Luetolf, Peter

2006-07-01

An extended model for iontophoretic enhancement of transdermal drug permeation under constant voltage is described based on the previously modified Nernst-Planck equation, which included the effect of convective solvent flow. This model resulted in an analytical expression for the enhancement factor as a function of applied voltage, convective flow velocity due to electroosmosis, ratio of lipid to aqueous pathway passive permeability, and weighted average net ionic valence of the permeant in the aqueous epidermis domain. The shift of pH in the epidermis compared to bulk caused by the electrical double layer at the lipid-aqueous domain interface was evaluated using the Poisson-Boltzmann equation. This was solved numerically for representative surface charge densities and yielded pH differences between bulk and epidermal aqueous domain between 0.05 and 0.4 pH units. The developed model was used to analyze the experimental enhancement of an amphoteric weak electrolyte measured in vitro using human cadaver epidermis and a voltage of 250 mV at different pH values. Parameter values characterizing the involved factors were determined that yielded the experimental enhancement factors and passive permeability coefficients at all pH values. The model provided a very good agreement between experimental and calculated enhancement and passive permeability. The deduced parameters showed (i) that the pH shift in the aqueous permeation pathway had a notable effect on the ionic valence and the partitioning of the drug in this domain for a high surface charge density and depending on the pK(a) and pI of the drug in relation to the bulk pH; (ii) the magnitude and the direction of convective transport due to electroosmosis typically reflected the density and sign, respectively, of surface charge of the tissue and its effect on enhancement was substantial for bulk pH values differing from the pI of epidermal tissue; (iii) the aqueous pathway predominantly determined passive permeability of the studied compound despite its measurable lipophilicity and therefore the lipid pathway did not notably affect enhancement. Hence, the proposed model can provide a good quantitative insight into the interplay between different phenomena and permeant properties influencing iontophoresis and can potentially be used as a predictive tool of the process.

Characterization of a fluvial aquifer at a range of depths and scales: the Triassic St Bees Sandstone Formation, Cumbria, UK

NASA Astrophysics Data System (ADS)

Medici, Giacomo; West, L. J.; Mountney, N. P.

2018-03-01

Fluvial sedimentary successions represent porous media that host groundwater and geothermal resources. Additionally, they overlie crystalline rocks hosting nuclear waste repositories in rift settings. The permeability characteristics of an arenaceous fluvial succession, the Triassic St Bees Sandstone Formation in England (UK), are described, from core-plug to well-test scale up to 1 km depth. Within such lithified successions, dissolution associated with the circulation of meteoric water results in increased permeability ( K 10-1-100 m/day) to depths of at least 150 m below ground level (BGL) in aquifer systems that are subject to rapid groundwater circulation. Thus, contaminant transport is likely to occur at relatively high rates. In a deeper investigation (> 150 m depth), where the aquifer has not been subjected to rapid groundwater circulation, well-test-scale hydraulic conductivity is lower, decreasing from K 10-2 m/day at 150-400 m BGL to 10-3 m/day down-dip at 1 km BGL, where the pore fluid is hypersaline. Here, pore-scale permeability becomes progressively dominant with increasing lithostatic load. Notably, this work investigates a sandstone aquifer of fluvial origin at investigation depths consistent with highly enthalpy geothermal reservoirs ( 0.7-1.1 km). At such depths, intergranular flow dominates in unfaulted areas with only minor contribution by bedding plane fractures. However, extensional faults represent preferential flow pathways, due to presence of high connective open fractures. Therefore, such faults may (1) drive nuclear waste contaminants towards the highly permeable shallow (< 150 m BGL) zone of the aquifer, and (2) influence fluid recovery in geothermal fields.

Universal scaling of permeability through the granular-to-continuum transition

NASA Astrophysics Data System (ADS)

Wadsworth, F. B.; Scheu, B.; Heap, M. J.; Kendrick, J. E.; Vasseur, J.; Lavallée, Y.; Dingwell, D. B.

2015-12-01

Magmas fragment forming a transiently granular material, which can weld back to a fluid-continuum. This process results in dramatic changes in the gas-volume fraction of the material, which impacts the gas permeability. We collate published data for the gas-volume fraction and permeability of volcanic and synthetic materials which have undergone this process to different amounts and note that in all cases there exists a discontinuity in the relationship between these two properties. By discriminating data for which good microstructural information are provided, we use simple scaling arguments to collapse the data in both the still-granular, high gas-volume fraction regime and the fluid-continuum low gas-volume fraction regime such that a universal description can be achieved. We use this to argue for the microstructural meaning of the well-described discontinuity between gas-permeability and gas-volume fraction and to infer the controls on the position of this transition between dominantly granular and dominantly fluid-continuum material descriptions. As a specific application, we consider the transiently granular magma transported through and deposited in fractures in more-coherent magmas, thought to be a primary degassing pathway in high viscosity systems. We propose that our scaling coupled with constitutive laws for densification can provide insights into the longevity of such degassing channels, informing sub-surface pressure modelling at such volcanoes.

Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery

PubMed Central

Kumar, Niyanta N.; Gautam, Mohan; Lochhead, Jeffrey J.; Wolak, Daniel J.; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G.

2016-01-01

Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID:27558973

Visceral adipose tissue and leptin increase colonic epithelial tight junction permeability via a RhoA-ROCK-dependent pathway.

PubMed

Le Dréan, Gwenola; Haure-Mirande, Vianney; Ferrier, Laurent; Bonnet, Christian; Hulin, Philippe; de Coppet, Pierre; Segain, Jean-Pierre

2014-03-01

Proinflammatory cytokines produced by immune cells play a central role in the increased intestinal epithelial permeability during inflammation. Expansion of visceral adipose tissue (VAT) is currently considered a consequence of intestinal inflammation. Whether VAT per se plays a role in early modifications of intestinal barrier remains unknown. The aim of this study was to demonstrate the direct role of adipocytes in regulating paracellular permeability of colonic epithelial cells (CECs). We show in adult rats born with intrauterine growth retardation, a model of VAT hypertrophy, and in rats with VAT graft on the colon, that colonic permeability was increased without any inflammation. This effect was associated with altered expression of tight junction (TJ) proteins occludin and ZO-1. In coculture experiments, adipocytes decreased transepithelial resistance (TER) of Caco-2 CECs and induced a disorganization of ZO-1 on TJs. Intraperitoneal administration of leptin to lean rats increased colonic epithelial permeability and altered ZO-1 expression and organization. Treatment of HT29-19A CECs with leptin, but not adiponectin, dose-dependently decreased TER and altered TJ and F-actin cytoskeleton organization through a RhoA-ROCK-dependent pathway. Our data show that adipocytes and leptin directly alter TJ function in CECs and suggest that VAT could impair colonic epithelial barrier.

A Framework for Fracture Network Formation in Overpressurised Impermeable Shale: Deformability Versus Diagenesis

NASA Astrophysics Data System (ADS)

Alevizos, Sotiris; Poulet, Thomas; Sari, Mustafa; Lesueur, Martin; Regenauer-Lieb, Klaus; Veveakis, Manolis

2017-03-01

Understanding the formation, geometry and fluid connectivity of nominally impermeable unconventional shale gas and oil reservoirs is crucial for safe unlocking of these vast energy resources. We present a recent discovery of volumetric instabilities of ductile materials that may explain why impermeable formations become permeable. Here, we present the fundamental mechanisms, the critical parameters and the applicability of the novel theory to unconventional reservoirs. We show that for a reservoir under compaction, there exist certain ambient and permeability conditions at which diagenetic (fluid-release) reactions may provoke channelling localisation instabilities. These channels are periodically interspersed in the matrix and represent areas where the excess fluid from the reaction is segregated at high velocity. We find that channelling instabilities are favoured from pore collapse features for extremely low-permeability formations and fluid-release diagenetic reactions, therefore providing a natural, periodic network of efficient fluid pathways in an otherwise impermeable matrix (i.e. fractures). Such an outcome is of extreme importance the for exploration and extraction phases of unconventional reservoirs.

Perfluorohexadecanoic acid increases paracellular permeability in endothelial cells through the activation of plasma kallikrein-kinin system.

PubMed

Liu, Qian S; Hao, Fang; Sun, Zhendong; Long, Yanmin; Zhou, Qunfang; Jiang, Guibin

2018-01-01

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous and high persistent in human blood, thus potentially inducing a myriad of deleterious consequences. Plasma kallikrein-kinin system (KKS), which physiologically regulates vascular permeability, is vulnerable to exogenous stimulators, like PFASs with long-chain alkyl backbone substituted by electronegative fluorine. The study on the interactions of PFASs with the KKS and the subsequent effects on vascular permeability would be helpful to illustrate how the chemicals penetrate the biological vascular barriers to reach different tissues. In present study, three representative PFASs, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexadecanoic acid (PFHxDA), were investigated for their effects on the activation of the KKS, paracellular permeability in human retina endothelial cells (HRECs) and integrity of the adherens junctions. In contrast to either PFOS or PFOA, PFHxDA efficiently triggered KKS activation in a concentration-dependent manner based on protease activity assays. The plasma activated by PFHxDA significantly increased paracellular permeability of HRECs through the degradation of adherens junctions. As evidenced by the antagonistic effect of aprotinin, PFHxDA-involved effects on vascular permeability were mediated by KKS activation. The results herein firstly revealed the mechanistic pathway for PFHxDA induced effects on vascular endothelial cells. Regarding the possible structure-related activities of the chemicals, this finding would be of great help in the risk assessment of PFASs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Puerarin transport across a Calu-3 cell monolayer - an in vitro model of nasal mucosa permeability and the influence of paeoniflorin and menthol.

PubMed

Zhang, Lin; Du, Shou-Ying; Lu, Yang; Liu, Chang; Tian, Zhi-Hao; Yang, Chang; Wu, Hui-Chao; Wang, Zhen

2016-01-01

Nasal administration is a high-potential delivery system, particularly because it can provide a pathway from the nose to the brain. The objective of this research is to characterize puerarin transport across a Calu-3 cell monolayer used as a model of the nasal mucosa and to evaluate the influence of puerarin in combination with paeoniflorin and menthol to explore the enhanced mechanism of the permeability at the cell level. The apparent permeability coefficients (P app) of puerarin bidirectional transport were both <1.5×10(-6) cm/s, and the efflux ratio was <1.5, indicating that puerarin alone exhibited poor absorption and that its transport primarily occurred by passive diffusion through the cell monolayer. When puerarin was coad ministered with paeoniflorin, the P app was not changed (P>0.05). However, the addition of menthol significantly (P<0.05) improved the P app of puerarin in both directions. Moreover, based on immunofluorescence experiments and transepithelial electrical resistance measurements, the data indicated that the drug compatibility opened tight junctions and weakened the barrier capabilities of epithelial cells, thereby promoting the permeability of puerarin.

Cardiotoxicity of acetogenins from Persea americana occurs through the mitochondrial permeability transition pore and caspase-dependent apoptosis pathways.

PubMed

Silva-Platas, Christian; García, Noemí; Fernández-Sada, Evaristo; Dávila, Daniel; Hernández-Brenes, Carmen; Rodríguez, Dariana; García-Rivas, Gerardo

2012-08-01

Acetogenins are cell-membrane permeable, naturally occurring secondary metabolites of plants such as Annonaceae, Lauraceae and other related phylogenic families. They belong to the chemical derivatives of polyketides, which are synthesized from fatty acid precursors. Although acetogenins have displayed diverse biological activities, the anti-proliferative effect on human cancer cells has been widely reported. Acetogenins are inhibitors of complex I in the electron transport chain therefore they interrupt ATP synthesis in mitochondria. We tested a new acetogenins-enriched extract from the seed of Persea americana in order to investigate if any toxicity was induced on cardiac tissue and determine the involved mechanism. In isolated perfused heart we found that contractility was completely inhibited at an accumulative dose of 77 μg/ml. In isolated cardiomyocytes, the acetogenins-enriched extract induced apoptosis through the activation of the intrinsic pathway at 43 μg/ml. In isolated mitochondria, it inhibited complex I activity on NADH-linked respiration, as would be expected, but also induced permeability transition on succinate-linked respiration. Cyclosporine A, a known blocker of permeability transition, significantly prevented the permeability transition triggered by the acetogenins-enriched extract. In addition, our acetogenins-enriched extract inhibited ADP/ATP exchange, suggesting that an important element in phosphate or adenylate transport was affected. In this manner we suggest that acetogenins-enriched extract from Persea americana could directly modulate permeability transition, an entity not yet associated with the acetogenins' direct effects, resulting in cardiotoxicity.

Estimation and upscaling of dual-permeability model parameters for the transport of E.coli D21g in soils with preferential flow

USDA-ARS?s Scientific Manuscript database

Dual-permeability models are increasingly used to quantify the transport of solutes and microorganisms in soils with preferential flow. An ability to accurately determine the model parameters and their variation with preferential pathway characteristics is crucial for predicting the transport of mi...

Innovative computational tools for reducing exploration risk through integration of water-rock interactions and magnetotelluric surveys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Joseph

2017-04-20

Mapping permeability distributions in geothermal reservoirs is essential for reducing the cost of geothermal development. To avoid the cost and sampling bias of measuring permeability directly through drilling, we require remote methods of imaging permeability such as geophysics. Electrical resistivity (or its inverse, conductivity) is one of the most sensitive geophysical properties known to reflect long range fluid interconnection and thus the likelihood of permeability. Perhaps the most widely applied geophysical methods for imaging subsurface resistivity is magnetotellurics (MT) due to its relatively great penetration depths. A primary goal of this project is to confirm through ground truthing at existingmore » geothermal systems that MT resistivity structure interpreted integratively is capable of revealing permeable fluid pathways into geothermal systems.« less

Prominence of ichnologically influenced macroporosity in the karst Biscayne aquifer: Stratiform "super-K" zones

USGS Publications Warehouse

Cunningham, K.J.; Sukop, M.C.; Huang, H.; Alvarez, P.F.; Curran, H.A.; Renken, R.A.; Dixon, J.F.

2009-01-01

A combination of cyclostratigraphic, ichnologic, and borehole geophysical analyses of continuous core holes; tracer-test analyses; and lattice Boltzmann flow simulations was used to quantify biogenic macroporosity and permeability of the Biscayne aquifer, southeastern Florida. Biogenic macroporosity largely manifests as: (1) ichnogenic macroporosity primarily related to postdepositional burrowing activity by callianassid shrimp and fossilization of components of their complex burrow systems (Ophiomorpha); and (2) biomoldic macroporosity originating from dissolution of fossil hard parts, principally mollusk shells. Ophiomorpha-dominated ichno-fabric provides the greatest contribution to hydrologic characteristics in the Biscayne aquifer in a 345 km2 study area. Stratiform tabular-shaped units of thalassinidean-associated macroporosity are commonly confined to the lower part of upward-shallowing high-frequency cycles, throughout aggradational cycles, and, in one case, they stack vertically within the lower part of a high-frequency cycle set. Broad continuity of many of the macroporous units concentrates groundwater flow in extremely permeable passage-ways, thus making the aquifer vulnerable to long-distance transport of contaminants. Ichnogenic macroporosity represents an alternative pathway for concentrated groundwater flow that differs considerably from standard karst flow-system paradigms, which describe groundwater movement through fractures and cavernous dissolution features. Permeabilities were calculated using lattice Boltzmann methods (LBMs) applied to computer renderings assembled from X-ray computed tomography scans of various biogenic macroporous limestone samples. The highest simulated LBM permeabilities were about five orders of magnitude greater than standard laboratory measurements using air-permeability methods, which are limited in their application to extremely permeable macroporous rock samples. Based on their close conformance to analytical solutions for pipe flow, LBMs offer a new means of obtaining accurate permeability values for such materials. We suggest that the stratiform ichnogenic groundwater flow zones have permeabilities even more extreme (???2-5 orders of magnitude higher) than the Jurassic "super-K" zones of the giant Ghawar oil field. The flow zones of the Pleistocene Biscayne aquifer provide examples of ichnogenic macroporosity for comparative analysis of origin and evolution in other carbonate aquifers, as well as petroleum reservoirs. ?? 2008 Geological Society of America.

Outer Membrane Permeability of Cyanobacterium Synechocystis sp. Strain PCC 6803: Studies of Passive Diffusion of Small Organic Nutrients Reveal the Absence of Classical Porins and Intrinsically Low Permeability

PubMed Central

Kowata, Hikaru; Tochigi, Saeko; Takahashi, Hideyuki

2017-01-01

ABSTRACT The outer membrane of heterotrophic Gram-negative bacteria plays the role of a selective permeability barrier that prevents the influx of toxic compounds while allowing the nonspecific passage of small hydrophilic nutrients through porin channels. Compared with heterotrophic Gram-negative bacteria, the outer membrane properties of cyanobacteria, which are Gram-negative photoautotrophs, are not clearly understood. In this study, using small carbohydrates, amino acids, and inorganic ions as permeation probes, we determined the outer membrane permeability of Synechocystis sp. strain PCC 6803 in intact cells and in proteoliposomes reconstituted with outer membrane proteins. The permeability of this cyanobacterium was >20-fold lower than that of Escherichia coli. The predominant outer membrane proteins Slr1841, Slr1908, and Slr0042 were not permeable to organic nutrients and allowed only the passage of inorganic ions. Only the less abundant outer membrane protein Slr1270, a homolog of the E. coli export channel TolC, was permeable to organic solutes. The activity of Slr1270 as a channel was verified in a recombinant Slr1270-producing E. coli outer membrane. The lack of putative porins and the low outer membrane permeability appear to suit the cyanobacterial autotrophic lifestyle; the highly impermeable outer membrane would be advantageous to cellular survival by protecting the cell from toxic compounds, especially when the cellular physiology is not dependent on the uptake of organic nutrients. IMPORTANCE Because the outer membrane of Gram-negative bacteria affects the flux rates for various substances into and out of the cell, its permeability is closely associated with cellular physiology. The outer membrane properties of cyanobacteria, which are photoautotrophic Gram-negative bacteria, are not clearly understood. Here, we examined the outer membrane of Synechocystis sp. strain PCC 6803. We revealed that it is relatively permeable to inorganic ions but is markedly less permeable to organic nutrients, with >20-fold lower permeability than the outer membrane of Escherichia coli. Such permeability appears to fit the cyanobacterial lifestyle, in which the diffusion pathway for inorganic solutes may suffice to sustain the autotrophic physiology, illustrating a link between outer membrane permeability and the cellular lifestyle. PMID:28696278

Hydraulic fracturing fluid migration in the subsurface: A review and expanded modeling results

NASA Astrophysics Data System (ADS)

Birdsell, Daniel T.; Rajaram, Harihar; Dempsey, David; Viswanathan, Hari S.

2015-09-01

Understanding the transport of hydraulic fracturing (HF) fluid that is injected into the deep subsurface for shale gas extraction is important to ensure that shallow drinking water aquifers are not contaminated. Topographically driven flow, overpressured shale reservoirs, permeable pathways such as faults or leaky wellbores, the increased formation pressure due to HF fluid injection, and the density contrast of the HF fluid to the surrounding brine can encourage upward HF fluid migration. In contrast, the very low shale permeability and capillary imbibition of water into partially saturated shale may sequester much of the HF fluid, and well production will remove HF fluid from the subsurface. We review the literature on important aspects of HF fluid migration. Single-phase flow and transport simulations are performed to quantify how much HF fluid is removed via the wellbore with flowback and produced water, how much reaches overlying aquifers, and how much is permanently sequestered by capillary imbibition, which is treated as a sink term based on a semianalytical, one-dimensional solution for two-phase flow. These simulations include all of the important aspects of HF fluid migration identified in the literature review and are performed in five stages to faithfully represent the typical operation of a hydraulically fractured well. No fracturing fluid reaches the aquifer without a permeable pathway. In the presence of a permeable pathway, 10 times more fracturing fluid reaches the aquifer if well production and capillary imbibition are not included in the model.

Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats.

PubMed

Li, Hui-Qin; Li, Yan; Chen, Zi-Xian; Zhang, Xiao-Guang; Zheng, Xia-Wei; Yang, Wen-Ting; Chen, Shuang; Zheng, Guo-Qing

2016-01-01

Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20) exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa's scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH ( P < 0.05). In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

GLUTAMATE METABOLISM IN BRUCELLA ABORTUS STRAINS OF LOW AND HIGH VIRULENCE

PubMed Central

Dasinger, B. L.; Wilson, J. B.

1962-01-01

Dasinger, B. L. (University of Wisconsin, Madison) and J. B. Wilson. Glutamate metabolism in Brucella abortus strains of low and high virulence. J. Bacteriol. 84:911–915. 1962.—Brucella abortus strains of low virulence oxidize glutamate at a high rate, whereas strains of high virulence oxidize glutamate at a relatively low rate. Results indicated that this observation was not related to differences in pathway of glutamate oxidation or to differences in total enzyme activity. Permeability studies showed that the maximal rates of glutamate accumulation were 2.8 μmoles per 2 min per g (wet wt) for a strain of high virulence and 6.2 μmoles per 2 min per g for a strain of low virulence, but equal intracellular steady-state concentrations were attained by both types of strains. Evidence is presented which suggests that the site of glutamate oxidation is separate from the pool of glutamate being measured. Unequal rates of permeability at these sites could be the reason for the differences in rate of glutamate oxidation. PMID:14028057

Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways

DOE PAGES

DeLoache, William C.; Russ, Zachary N.; Dueber, John E.

2016-03-30

Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a sensitive high-throughput assay for peroxisomal cargo import. We identify an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non-native cargo proteins. Additionally, we perform the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay. Finally, we apply these new insights to compartmentalize a two-enzymemore » pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titre. Lastly, this work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeLoache, William C.; Russ, Zachary N.; Dueber, John E.

Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a sensitive high-throughput assay for peroxisomal cargo import. We identify an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non-native cargo proteins. Additionally, we perform the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay. Finally, we apply these new insights to compartmentalize a two-enzymemore » pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titre. Lastly, this work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

The role of mitosis in LDL transport through cultured endothelial cell monolayers.

PubMed

Cancel, Limary M; Tarbell, John M

2011-03-01

We (7) have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for LDL transport under convective conditions, accounting for >90% of the transport. We (8) have also recently shown that the permeability of bovine aortic endothelial cell monolayers is highly correlated with their rate of apoptosis and that inhibiting apoptosis lowers the permeability of the monolayers to LDL. To explore the role of mitosis in the leaky junction pathway, the microtubule-stabilizing agent paclitaxel was used to alter the rate of mitosis, and LDL flux and water flux (J(v)) were measured. Control monolayers had an average mitosis rate of 0.029%. Treatment with paclitaxel (2.5 μM) for 1.5, 3, 4.5, or 6 h yielded increasing rates of mitosis ranging from 0.099% to 1.03%. The convective permeability of LDL (P(e)) increased up to fivefold, whereas J(v) increased up to threefold, over this range of mitosis rates. We found strong correlations between the mitosis rate and both P(e) and J(v). However, compared with our previous apoptosis study (8), we found that mitosis was only half as effective as apoptosis in increasing P(e). The results led us to conclude that while mitosis-related leaky junctions might play a role in the initial infiltration of LDL into the artery wall, the progression of atherosclerosis might be more closely correlated with apoptosis-related leaky junctions.

Zea mays Annexins Modulate Cytosolic Free Ca2+ and Generate a Ca2+-Permeable Conductance[W

PubMed Central

Laohavisit, Anuphon; Mortimer, Jennifer C.; Demidchik, Vadim; Coxon, Katy M.; Stancombe, Matthew A.; Macpherson, Neil; Brownlee, Colin; Hofmann, Andreas; Webb, Alex A.R.; Miedema, Henk; Battey, Nicholas H.; Davies, Julia M.

2009-01-01

Regulation of reactive oxygen species and cytosolic free calcium ([Ca2+]cyt) is central to plant function. Annexins are small proteins capable of Ca2+-dependent membrane binding or membrane insertion. They possess structural motifs that could support both peroxidase activity and calcium transport. Here, a Zea mays annexin preparation caused increases in [Ca2+]cyt when added to protoplasts of Arabidopsis thaliana roots expressing aequorin. The pharmacological profile was consistent with annexin activation (at the extracellular plasma membrane face) of Arabidopsis Ca2+-permeable nonselective cation channels. Secreted annexins could therefore modulate Ca2+ influx. As maize annexins occur in the cytosol and plasma membrane, they were incorporated at the intracellular face of lipid bilayers designed to mimic the plasma membrane. Here, they generated an instantaneously activating Ca2+-permeable conductance at mildly acidic pH that was sensitive to verapamil and Gd3+ and had a Ca2+-to-K+ permeability ratio of 0.36. These results suggest that cytosolic annexins create a Ca2+ influx pathway directly, particularly during stress responses involving acidosis. A maize annexin preparation also demonstrated in vitro peroxidase activity that appeared independent of heme association. In conclusion, this study has demonstrated that plant annexins create Ca2+-permeable transport pathways, regulate [Ca2+]cyt, and may function as peroxidases in vitro. PMID:19234085

Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage

PubMed Central

Johnson, Anthea; Singhal, Naresh

2015-01-01

The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA)), transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency. PMID:26512647

Non-nucleoside reverse transcriptase inhibitor efavirenz increases monolayer permeability of human coronary artery endothelial cells

PubMed Central

Jamaluddin, Md Saha; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

2009-01-01

Highly active antiretroviral therapy (HAART) is often associated with endothelial dysfunction and cardiovascular complications. In this study, we determined whether HIV non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) could increase endothelial permeability. Human coronary artery endothelial cells (HCAECs) were treated with EFV (1, 5 and 10 µg/ml) and endothelial permeability was determined by a transwell system with a fluorescence-labeled dextran tracer. HCAECs treated with EFV showed a significant increase of endothelial permeability in a concentration-dependent manner. With real time PCR analysis, EFV significantly reduced the mRNA levels of tight junction proteins claudin-1, occludin, zonula occluden-1 and junctional adhesion molecule-1 compared with controls (P < 0.05). Protein levels of these tight junction molecules were also reduced substantially in the EFV-treated cells by western blot and flow cytometry analyses. In addition, EFV also increased superoxide anion production with dihydroethidium and cellular glutathione assays, while it decreased mitochondrial membrane potential with JC-staining. Antioxidants (ginkgolide B and MnTBAP) effectively blocked EFV-induced endothelial permeability and mitochondrial dysfunction. Furthermore, EFV increased the phosphorylation of MAPK JNK and IκBα, thereby increasing NFκB translocation to the nucleus. Chemical JNK inhibitor and dominant negative mutant JNK and IkBa adenoviruses effectively blocked the effects of EFV on HCAECs. Thus, EFV increases endothelial permeability which may be due to the decrease of tight junction proteins and the increase of superoxide anion. JNK and NFκB activation may be directly involved in the signal transduction pathway of EFV action in HCAECs. PMID:19674747

Geometric Analysis of Vein Fracture Networks From the Awibengkok Core, Indonesia

NASA Astrophysics Data System (ADS)

Khatwa, A.; Bruhn, R. L.; Brown, S. R.

2003-12-01

Fracture network systems within rocks are important features for the transportation and remediation of hazardous waste, oil and gas production, geothermal energy extraction and the formation of vein fillings and ore deposits. A variety of methods, including computational and laboratory modeling have been employed to further understand the dynamic nature of fractures and fracture systems (e.g. Ebel and Brown, this session). To substantiate these studies, it is also necessary to analyze the characteristics and morphology of naturally occurring vein systems. The Awibengkok core from a geothermal system in West Java, Indonesia provided an excellent opportunity to study geometric and petrologic characteristics of vein systems in volcanic rock. Vein minerals included chlorite, calcite, quartz, zeolites and sulphides. To obtain geometric data on the veins, we employed a neural net image processing technique to analyze high-resolution digital photography of the veins. We trained a neural net processor to map the extent of the vein using RGB pixel training classes. The resulting classification image was then converted to a binary image file and processed through a MatLab program that we designed to calculate vein geometric statistics, including aperture and roughness. We also performed detailed petrographic and microscopic geometric analysis on the veins to determine the history of mineralization and fracturing. We found that multi-phase mineralization due to chemical dissolution and re-precipitation as well as mechanical fracturing was a common feature in many of the veins and that it had a significant role for interpreting vein tortuosity and history of permeability. We used our micro- and macro-scale observations to construct four hypothetical permeability models that compliment the numerical and laboratory modeled data reported by Ebel and Brown. In each model, permeability changes, and in most cases fluctuates, differently over time as the tortuosity and aperture of veins are affected by the precipitation, dissolution, and re-precipitation of minerals, and also by mechanical fracturing. In all of our cases we interpret a first-phase mineral dissolution stage where permeability gradually declines as the vein is blocked by inward growing minerals. Hereafter, permeability may briefly increase with the onset of internal fracturing within the vein or by a phase of mineral dissolution opening up new pathways for fluid flow. Eventually we infer that permeability will decline again as second stage minerals are deposited in the fluid flow pathways.

Alternating current (AC) iontophoretic transport across human epidermal membrane: effects of AC frequency and amplitude.

PubMed

Yan, Guang; Xu, Qingfang; Anissimov, Yuri G; Hao, Jinsong; Higuchi, William I; Li, S Kevin

2008-03-01

As a continuing effort to understand the mechanisms of alternating current (AC) transdermal iontophoresis and the iontophoretic transport pathways in the stratum corneum (SC), the objectives of the present study were to determine the interplay of AC frequency, AC voltage, and iontophoretic transport of ionic and neutral permeants across human epidermal membrane (HEM) and use AC as a means to characterize the transport pathways. Constant AC voltage iontophoresis experiments were conducted with HEM in 0.10 M tetraethyl ammonium pivalate (TEAP). AC frequencies ranging from 0.0001 to 25 Hz and AC applied voltages of 0.5 and 2.5 V were investigated. Tetraethyl ammonium (TEA) and arabinose (ARA) were the ionic and neutral model permeants, respectively. In data analysis, the logarithm of the permeability coefficients of HEM for the model permeants was plotted against the logarithm of the HEM electrical resistance for each AC condition. As expected, linear correlations between the logarithms of permeability coefficients and the logarithms of resistances of HEM were observed, and the permeability data were first normalized and then compared at the same HEM electrical resistance using these correlations. Transport enhancement of the ionic permeant was significantly larger than that of the neutral permeant during AC iontophoresis. The fluxes of the ionic permeant during AC iontophoresis of 2.5 V in the frequency range from 5 to 1,000 Hz were relatively constant and were approximately 4 times over those of passive transport. When the AC frequency decreased from 5 to 0.001 Hz at 2.5 V, flux enhancement increased to around 50 times over passive transport. While the AC frequency for achieving the full effect of iontophoretic enhancement at low AC frequency was lower than anticipated, the frequency for approaching passive diffusion transport at high frequency was higher than expected from the HEM morphology. These observations are consistent with a transport model of multiple barriers in series and the previous hypothesis that the iontophoresis pathways across HEM under AC behave like a series of reservoirs interconnected by short pore pathways.

Concentration dependence of the cell membrane permeability to cryoprotectant and water and implications for design of methods for post-thaw washing of human erythrocytes.

PubMed

Lahmann, John M; Benson, James D; Higgins, Adam Z

2018-02-01

For more than fifty years the human red blood cell (RBC) has been a widely studied model for transmembrane mass transport. Existing literature spans myriad experimental designs with varying results and physiologic interpretations. In this review, we examine the kinetics and mechanisms of membrane transport in the context of RBC cryopreservation. We include a discussion of the pathways for water and glycerol permeation through the cell membrane and the implications for mathematical modeling of the membrane transport process. In particular, we examine the concentration dependence of water and glycerol transport and provide equations for estimating permeability parameters as a function of concentration based on a synthesis of literature data. This concentration-dependent transport model may allow for design of improved methods for post-thaw removal of glycerol from cryopreserved blood. More broadly, the consideration of the concentration dependence of membrane permeability parameters may be important for other cell types as well, especially for design of methods for equilibration with the highly concentrated solutions used for vitrification. Copyright © 2017 Elsevier Inc. All rights reserved.

Getting the gas out - developing gas networks in magmatic systems

NASA Astrophysics Data System (ADS)

Cashman, Katharine; Rust, Alison; Oppenheimer, Julie; Belien, Isolde

2015-04-01

Volcanic eruption style, and explosive potential, are strongly controlled by the pre-eruptive history of the magmatic volatiles: specifically, the more efficient the gas loss prior to eruption, the lower the likelihood of primary (magmatic) explosive activity. Commonly considered gas loss mechanisms include separated flow, where individual bubbles (or bubble clouds) travel at a rate that is faster than the host magma, and permeable flow, where gas escapes through permeable (connected) pathways developed within a (relatively) static matrix. Importantly, gas loss via separated flow is episodic, while gas loss via permeable flow is likely to be continuous. Analogue experiments and numerical models on three phase (solid-liquid-gas) systems also suggest a third mechanism of gas loss that involves the opening and closing of 'pseudo fractures'. Pseudo fractures form at a critical crystallinity that is close to the maximum particle packing. Fractures form by local rearrangement of solid particles and liquid to form a through-going gas fracture; gas escape is episodic, and modulated by the available gas volume and the rate of return flow of interstitial liquid back into the fracture. In all of the gas escape scenarios described above, a fundamental control on gas behaviour is the melt viscosity, which affects the rate of individual bubble rise, the rate of bubble expansion, the rate of film thinning (required for bubble coalescence), and the rate of melt flow into gas-generated fractures. From the perspective of magma degassing, rates of gas expansion and film thinning are key to the formation of an interconnected (permeable) gas pathway. Experiments with both analogue and natural materials show that bubble coalescence is relatively slow, and, in particle-poor melts, does not necessarily create permeable gas networks. As a result, degassing efficiency is modulated by the time scales required either (1) to produce large individual bubbles or bubble clouds (in low viscosity melts) or (2) to develop sufficient porosity for full connectivity of a bubble network (in high viscosity melts). In contrast, our experiments suggest that the presence of solid particles may greatly enhance gas escape. On the one hand, the addition of solid particles increases the bulk viscosity of the mixture, which reduces the migration rate of large single bubbles. On the other hand, the strength of networks created by touching crystals inhibits bulk magma deformation and forces smaller bubbles to deform to occupy the spaces between particles, thereby increasing both the bubble shape anisotropy and, correspondingly, the probability of bubble coalescence. Gas pathways created in this way take advantage of inhomogeneities in the spatial distribution of crystals and allow large-scale gas release at relatively low vesicularities. This mechanism of gas escape is likely to be important not only in mafic arc volcanoes, where shallow conduits are likely to be highly crystalline, but also for degassing of crystal-mush-dominated magmatic systems.

Effect of Permeation Enhancers on the Buccal Permeability of Nicotine: Ex vivo Transport Studies Complemented by MALDI MS Imaging.

PubMed

Marxen, Eva; Jin, Liang; Jacobsen, Jette; Janfelt, Christian; Hyrup, Birgitte; Nicolazzo, Joseph A

2018-02-21

The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [ 3 H]-nicotine and [ 14 C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The distribution of nicotine, mannitol and permeation enhancers was imaged using using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). Despite STDC significantly increasing permeability of [ 14 C]-mannitol, no enhancing effect was seen on [ 3 H]-nicotine permeability with any of the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability, likely due to nicotine being retained in the donor compartment. The permeability results were complemented by the spatial distribution of nicotine and mannitol determined with MALDI MSI. The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.

Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

PubMed

Avaritt, Brittany R; Swaan, Peter W

2014-09-01

Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

Permeability Evolution of Fractured Anhydrite Caused by Chemical and Mechanical Alteration

NASA Astrophysics Data System (ADS)

Detwiler, R. L.; Elkhoury, J. E.; Ameli, P.

2011-12-01

Geologic carbon sequestration requires competent structural seals (caprock) to prevent leakage over decadal time scales. Injection of large volumes of CO2 perturbs the target formation from chemical and mechanical equilibrium leading to the possible creation or enhancement of leakage pathways. We investigate the potential for leakage pathways (fractures) to grow over time under reservoir conditions in a series of anhydrite (Ca2SO4) cores. To simulate a potential leakage event in the laboratory, we fractured and jacketed the cores, and placed them in a flow-through reactor vessel. A high-pressure syringe pump applied confining stresses ranging from 7 to 17 MPa and another syringe pump pushed water through the sample at a constant flow rate with pressure control at the outlet. Effluent was sampled periodically and analyzed for Ca2+ and SO42- using an ion chromatograph. Before and after each experiment, we characterized the surfaces of the fractures using a high-resolution optical profilometer and a scanning electron microscope. Careful alignment of the surfaces during optical profiling allowed reproduction of the fracture aperture before and after each experiment. We present results from several experiments each carried out under different conditions in similar fractured anhydrite cores. One involved a well-mated pre-existing fracture and results showed that the permeability of the fractured core was similar to the intact rock matrix (O(10-18 m2); chemical alteration of the core was largely limited to the inflow face of the core and the fracture surfaces remained largely unaltered. To enhance permeability during subsequent experiments, we imposed a small (380 μm) shear displacement between the fracture surfaces resulting in a four-order-of-magnitude increase in initial permeability. The first of these was run at a constant flow rate of 0.6 ml/min for a period of 7 days. The measured pressure gradient within the core increased slowly for a period of 4 days followed by a rapid increase in differential pressure corresponding to a two-order-of-magnitude decrease in permeability. During the experiment, the diameter of the core decreased by ~300 μm at the inlet and a skin of gypsum (Ca2SO42H2O) was created along the length of the fracture. Dissolution of anhydrite and transition to gypsum of additional anhydrite weakened the fracture surfaces leading to closure of the fracture with a corresponding reduction in aperture and permeability. Additional experiments explore the influence of flow at a lower flow rate, which, in the absence of a large confining stress, has been shown to lead to the development of dissolution channels or wormholes.

Combining High Resolution InSAR and infrared photogrammetry for studying dome degassing and densification mechanisms at Volcán de Colima, Mexico

NASA Astrophysics Data System (ADS)

Salzer, Jacqueline T.; Milillo, Pietro; Varley, Nick; Perissin, Daniele; Pantaleo, Michele; Walter, Thomas R.

2017-04-01

Active volcanoes often display cyclic behaviour with alternating quiescent and eruptive periods. Continuously monitoring volcanic processes such as deformation, seismicity and degassing, irrespective of their current status, is crucial for understanding the parameters governing the fluid transport within the edifice and the transitions between different regimes. However, mapping the deformation and details of fluid escape at the summit of steep sloped volcanoes and integrating these with other types of data is challenging. Here we present for the first time the near-3D surface deformation field derived from high resolution radar interferometry (InSAR) acquired by the satellite TerraSAR-X at a degassing volcano dome and interpret the results in combination with overflight infrared and topographic data. We find that the results strongly differ depending on the chosen InSAR time series method, which potentially overprints the true physical complexities of small scale, shallow deformation processes. We present a new method for accurate mapping of heterogeneities in the dome deformation, and comparison to the topography and precisely located surface temperature anomalies. The identified deformation is dominated by strong but highly localized subsidence of the summit dome. Our results highlight the competing effects of the topography, permeability and shallow volcanic structures controlling the degassing pathways. On small spatial scales compaction sufficiently reduced the dome permeability to redirect the fluid flow. High resolution InSAR monitoring of volcanic domes thus provides valuable data for constraining models of their internal structure, degassing pathways and densification processes.

Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure.

PubMed

Wang, Li-Feng; Li, Xiang; Gao, Ya-Bing; Wang, Shui-Ming; Zhao, Li; Dong, Ji; Yao, Bin-Wei; Xu, Xin-Ping; Chang, Gong-Min; Zhou, Hong-Mei; Hu, Xiang-Jun; Peng, Rui-Yun

2015-08-01

Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

A prospective analysis of co-processed non-ionic surfactants in enhancing permeability of a model hydrophilic drug.

PubMed

Alvi, Mohammed M; Chatterjee, Parnali

2014-04-01

Paracellular route is a natural pathway for the transport of many hydrophilic drugs and macromolecules. The purpose of this study was to prospectively evaluate the ability of novel co-processed non-ionic surfactants to enhance the paracellular permeability of a model hydrophilic drug metformin using Caco-2 (human colonic adenocarcinoma) cell model. A three-tier screen was undertaken to evaluate the co-processed blends based on cytotoxicity, cellular integrity, and permeability coefficient. The relative contribution of the paracellular and the transcellular route in overall transport of metformin by co-processed blends was determined. Immunocytochemistry was conducted to determine the distribution of tight-junction protein claudin-1 after incubation with the co-processed blends. It was found that novel blends of Labrasol and Transcutol-P enhanced metformin permeability by approximately twofold with transient reduction in the transepithelia electrical resistance (TEER) and minimal cytotoxicity compared with the control, with the paracellular pathway as the major route of metformin transport. Maximum permeability of metformin (∼10-fold) was mediated by Tween-20 blends along with >75% reduction in the TEER which was irreversible over 24-h period. A shift in metformin transport from the paracellular to the transcellular route was observed with some Tween-20 blends. Immunocytochemical analysis revealed rearrangement of the cellular borders and fragmentation on treatment with Tween-20 blends. In conclusion, cytotoxicity, cellular integrity, and permeability of the hydrophilic drugs can be greatly influenced by the polyoxyethylene residues and medium chain fatty acids in the non-ionic surfactants at clinically relevant concentrations and therefore should be thoroughly investigated prior to their inclusion in formulations.

Roles of URLs in Probing Controls on Induced Seismicity and Permeability Evolution

NASA Astrophysics Data System (ADS)

Elsworth, D.

2014-12-01

The generation and extension of new fractures and the development of controlled slip and opening are an implicit component in both forming and in enhancing flow pathways to unlock hydrocarbons and geothermal energy in otherwise very low permeability formations. The opposite is true for containment structures and caprocks. The complex stress state coupled with pre-existing fracture networks means that new flow pathways may develop in complex ways including varied modes of dilatation and slip, deformation that may be seismic or aseismic and permeability that may net increase of decrease. Where this deformation relies on either the reactivation, extension or development of fractures, this evolution is intrinsically scale dependent requiring that an improved understanding of this dynamic response must interrogate its evolution at representative scales - scales of decimeters to a few meters. We explore the controls on instability through frictional slip and instability including changes related to environmental conditions and physical properties. The former relate to changes in effective stress driven by fluid pressures, thermal and chemical stresses and the latter to changes in strength and stability conditioned on initial or evolving mineralogy. We identify important contemporary questions that are intrinsically scale dependent and may be effectively probed by field experimentation linking deformation and permeability.

The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism

PubMed Central

Inserte, Javier; Garcia-Dorado, David

2015-01-01

Cardiomyocyte cell death occurring during myocardial reperfusion (reperfusion injury) contributes to final infarct size after transient coronary occlusion. Different interrelated mechanisms of reperfusion injury have been identified, including alterations in cytosolic Ca2+ handling, sarcoplasmic reticulum-mediated Ca2+ oscillations and hypercontracture, proteolysis secondary to calpain activation and mitochondrial permeability transition. All these mechanisms occur during the initial minutes of reperfusion and are inhibited by intracellular acidosis. The cGMP/PKG pathway modulates the rate of recovery of intracellular pH, but has also direct effect on Ca2+ oscillations and mitochondrial permeability transition. The cGMP/PKG pathway is depressed in cardiomyocytes by ischaemia/reperfusion and preserved by ischaemic postconditioning, which importantly contributes to postconditioning protection. The present article reviews the mechanisms and consequences of the effect of ischaemic postconditioning on the cGMP/PKG pathway, the different pharmacological strategies aimed to stimulate it during myocardial reperfusion and the evidence, limitations and promise of translation of these strategies to the clinical practice. Overall, the preclinical and clinical evidence suggests that modulation of the cGMP/PKG pathway may be a therapeutic target in the context of myocardial infarction. PMID:25297462

Numerical modeling of fracking fluid migration through fault zones and fractures in the North German Basin

NASA Astrophysics Data System (ADS)

Pfunt, Helena; Houben, Georg; Himmelsbach, Thomas

2016-09-01

Gas production from shale formations by hydraulic fracturing has raised concerns about the effects on the quality of fresh groundwater. The migration of injected fracking fluids towards the surface was investigated in the North German Basin, based on the known standard lithology. This included cases with natural preferential pathways such as permeable fault zones and fracture networks. Conservative assumptions were applied in the simulation of flow and mass transport triggered by a high pressure boundary of up to 50 MPa excess pressure. The results show no significant fluid migration for a case with undisturbed cap rocks and a maximum of 41 m vertical transport within a permeable fault zone during the pressurization. Open fractures, if present, strongly control the flow field and migration; here vertical transport of fracking fluids reaches up to 200 m during hydraulic fracturing simulation. Long-term transport of the injected water was simulated for 300 years. The fracking fluid rises vertically within the fault zone up to 485 m due to buoyancy. Progressively, it is transported horizontally into sandstone layers, following the natural groundwater flow direction. In the long-term, the injected fluids are diluted to minor concentrations. Despite the presence of permeable pathways, the injected fracking fluids in the reported model did not reach near-surface aquifers, either during the hydraulic fracturing or in the long term. Therefore, the probability of impacts on shallow groundwater by the rise of fracking fluids from a deep shale-gas formation through the geological underground to the surface is small.

Permeability evolution governed by shear: An example during spine extrusion at Unzen volcano, Japan

NASA Astrophysics Data System (ADS)

Ashworth, James; Lavallée, Yan; Wallace, Paul; Kendrick, Jackie; Coats, Rebecca; Miwa, Takahiro; Hess, Kai-Uwe

2017-04-01

A volcano's eruptive style is strongly controlled by the permeability of the magma and the surrounding edifice rock - explosive activity is more likely if exsolved gases cannot escape the system. In this study, we investigate how shear strain causes variations in permeability within a volcanic conduit, and discuss how spatio-temporal variation in shear regimes may develop. The eruption of Unzen volcano, Japan, which occurred between 1990 - 1995, culminated in the extrusion of a 60 metre-high dacitic spine. The spine, left exposed at the lava dome surface, displays the petrographic architecture of the magma in the shallow conduit. Observations and measurements made in the field are combined with laboratory experiments to understand the distribution of permeability in the shallow conduit. Examination of the lava dome led to the selection of two sites for detailed investigation. First, we examined a section of extruded spine 6 metres in width, which displays a transition from apparently unsheared rock in the conduit core to rocks exhibiting increasing shear towards the conduit margin, bounded by a fault gouge zone. Laboratory characterisation (mineralogy, porosity, permeability, X-ray tomography) was undertaken on these samples. In contrast, a second section of spine (extruded later during the eruption) exhibited a large tensile fracture, and this area was investigated using non-destructive in-situ permeability measurements. Our lab measurements show that in the first outcrop, permeability decreases across the shear zone from core to gouge by approximately one order of magnitude perpendicular to shear; a similar decrease is observed parallel to shear, but is less severe. The lowest permeability is observed in the most highly sheared block; here, permeability is 2.5 x10-14 m2 in the plane of shear and 9 x10-15 m2 perpendicular to shear. Our measurements clearly demonstrate the influence of shear on conduit permeability, with significant anisotropy in the shear zone. The sheared rocks are strongly micro-fractured, resulting in a porosity decrease of up to 4% and permeability decrease of over one order of magnitude with increasing effective pressure (effective pressure = confining pressure - pore pressure) between 5 - 100 MPa, representative of increasing lithostatic pressure from 200 m to 4 km depth in the crust. In contrast, our field study of the second spine section, which features a 2 cm wide by 3 metre-long tensile fracture flanked by a 40-cm wide shear damage zone, reveals that dilational shear can result in an increase in permeability of approximately three orders of magnitude. The contrasting shear zone characteristics can be attributed to different shear regimes, which likely occur at different depths in the conduit. At greater depth in the system, where lithostatic pressures largely exceed pore pressure, compactional shear appears to dominate, reducing the permeable porous network as magma strains along the conduit margin, whereas at shallower levels, where the effective pressure is low, dilational shear becomes dominant, resulting in the creation of permeable pathways. We conclude that contrasting shearing regimes may simultaneously affect magma ascent dynamics in volcanic conduits, causing a range of dynamic permeability variations (positive and negative), which dictate eruptive behaviour.

An experimental study of permeability development as a function of crystal-free melt viscosity

NASA Astrophysics Data System (ADS)

Lindoo, A.; Larsen, J. F.; Cashman, K. V.; Dunn, A. L.; Neill, O. K.

2016-02-01

Permeability development in magmas controls gas escape and, as a consequence, modulates eruptive activity. To date, there are few experimental controls on bubble growth and permeability development, particularly in low viscosity melts. To address this knowledge gap, we have run controlled decompression experiments on crystal-free rhyolite (76 wt.% SiO2), rhyodacite (70 wt.% SiO2), K-phonolite (55 wt.% SiO2) and basaltic andesite (54 wt.% SiO2) melts. This suite of experiments allows us to examine controls on the critical porosity at which vesiculating melts become permeable. As starting materials we used both fine powders and solid slabs of pumice, obsidian and annealed starting materials with viscosities of ∼102 to ∼106 Pas. We saturated the experiments with water at 900° (rhyolite, rhyodacite, and phonolite) and 1025 °C (basaltic andesite) at 150 MPa for 2-72 hrs and decompressed samples isothermally to final pressures of 125 to 10 MPa at rates of 0.25-4.11 MPa/s. Sample porosity was calculated from reflected light images of polished charges and permeability was measured using a bench-top gas permeameter and application of the Forchheimer equation to estimate both viscous (k1) and inertial (k2) permeabilities. Degassing conditions were assessed by measuring dissolved water contents using micro-Fourier-Transform Infrared (μ-FTIR) techniques. All experiment charges are impermeable below a critical porosity (ϕc) that varies among melt compositions. For experiments decompressed at 0.25 MPa/s, we find the percolation threshold for rhyolite is 68.3 ± 2.2 vol.%; for rhyodacite is 77.3 ± 3.8 vol.%; and for K-phonolite is 75.6 ± 1.9 vol.%. Rhyolite decompressed at 3-4 MPa/s has a percolation threshold of 74 ± 1.8 vol.%. These results are similar to previous experiments on silicic melts and to high permeability thresholds inferred for silicic pumice. All basaltic andesite melts decompressed at 0.25 MPa/s, in contrast, have permeabilities below the detection limit (∼10-15 m2), and a maximum porosity of 63 vol.%. Additionally, although the measured porosities of basaltic andesite experiments are ∼10-35 vol.% lower than calculated equilibrium porosities, μ-FTIR analyses confirm the basaltic andesite melts remained in equilibrium during degassing. We show that the low porosities and permeabilities are a consequence of short melt relaxation timescales during syn- and post-decompression degassing. Our results suggest that basaltic andesite melts reached ϕc > 63 vol.% and subsequently degassed; loss of internal bubble pressure caused the bubbles to shrink and their connecting apertures to seal before quench, closing the connected pathways between bubbles. Our results challenge the hypothesis that low viscosity melts have a permeability threshold of ∼30 vol.%, and instead support the high permeability thresholds observed in analogue experiments on low viscosity materials. Importantly, however, these low viscosity melts are unable to maintain high porosities once the percolation threshold is exceeded because of rapid outgassing and collapse of the permeable network. We conclude, therefore, that melt viscosity has little effect on percolation threshold development, but does influence outgassing.

Metabolomic profiles delineate the potential role of glycine in gold nanorod-induced disruption of mitochondria and blood-testis barrier factors in TM-4 cells

NASA Astrophysics Data System (ADS)

Xu, Bo; Chen, Minjian; Ji, Xiaoli; Mao, Zhilei; Zhang, Xuemei; Wang, Xinru; Xia, Yankai

2014-06-01

Gold nanorods (GNRs) are commonly used nanomaterials with potential harmful effects on male reproduction. However, the mechanism by which GNRs affect male reproduction remains largely undetermined. In this study, the metabolic changes in spermatocyte-derived cells GC-2 and Sertoli cell line TM-4 were analyzed after GNR treatment for 24 h. Metabolomic analysis revealed that glycine was highly decreased in TM-4 cells after GNR-10 nM treatment while there was no significant change in GC-2 cells. RT-PCR showed that the mRNA levels of glycine synthases in the mitochondrial pathway decreased after GNR treatment, while there was no significant difference in mRNA levels of glycine synthases in the cytoplasmic pathway. High content screening (HCS) showed that GNRs decreased membrane permeability and mitochondrial membrane potential of TM-4 cells, which was also confirmed by JC-1 staining. In addition, RT-PCR and Western blot indicated that the mRNA and protein levels of blood-testis barrier (BTB) factors (ZO-1, occludin, claudin-5, and connexin-43) in TM-4 cells were also disrupted by GNRs. After glycine was added into the medium, the GNR-induced harmful effects on mitochondria and BTB factors were recovered in TM-4 cells. Our results showed that even low doses of GNRs could induce significant toxic effects on mitochondria and BTB factors in TM-4 cells. Furthermore, we revealed that glycine was a potentially important metabolic intermediary for the changes of membrane permeability, mitochondrial membrane potential and BTB factors after GNR treatment in TM-4 cells.Gold nanorods (GNRs) are commonly used nanomaterials with potential harmful effects on male reproduction. However, the mechanism by which GNRs affect male reproduction remains largely undetermined. In this study, the metabolic changes in spermatocyte-derived cells GC-2 and Sertoli cell line TM-4 were analyzed after GNR treatment for 24 h. Metabolomic analysis revealed that glycine was highly decreased in TM-4 cells after GNR-10 nM treatment while there was no significant change in GC-2 cells. RT-PCR showed that the mRNA levels of glycine synthases in the mitochondrial pathway decreased after GNR treatment, while there was no significant difference in mRNA levels of glycine synthases in the cytoplasmic pathway. High content screening (HCS) showed that GNRs decreased membrane permeability and mitochondrial membrane potential of TM-4 cells, which was also confirmed by JC-1 staining. In addition, RT-PCR and Western blot indicated that the mRNA and protein levels of blood-testis barrier (BTB) factors (ZO-1, occludin, claudin-5, and connexin-43) in TM-4 cells were also disrupted by GNRs. After glycine was added into the medium, the GNR-induced harmful effects on mitochondria and BTB factors were recovered in TM-4 cells. Our results showed that even low doses of GNRs could induce significant toxic effects on mitochondria and BTB factors in TM-4 cells. Furthermore, we revealed that glycine was a potentially important metabolic intermediary for the changes of membrane permeability, mitochondrial membrane potential and BTB factors after GNR treatment in TM-4 cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01035c

The twisted ion-permeation pathway of a resting voltage-sensing domain.

PubMed

Tombola, Francesco; Pathak, Medha M; Gorostiza, Pau; Isacoff, Ehud Y

2007-02-01

Proteins containing voltage-sensing domains (VSDs) translate changes in membrane potential into changes in ion permeability or enzymatic activity. In channels, voltage change triggers a switch in conformation of the VSD, which drives gating in a separate pore domain, or, in channels lacking a pore domain, directly gates an ion pathway within the VSD. Neither mechanism is well understood. In the Shaker potassium channel, mutation of the first arginine residue of the S4 helix to a smaller uncharged residue makes the VSD permeable to ions ('omega current') in the resting conformation ('S4 down'). Here we perform a structure-guided perturbation analysis of the omega conductance to map its VSD permeation pathway. We find that there are four omega pores per channel, which is consistent with one conduction path per VSD. Permeating ions from the extracellular medium enter the VSD at its peripheral junction with the pore domain, and then plunge into the core of the VSD in a curved conduction pathway. Our results provide a model of the resting conformation of the VSD.

Physiological and biochemical characteristics of adrenergic receptors and pathways in brown adipocytes

NASA Technical Reports Server (NTRS)

Horwitz, B. A.

1975-01-01

Mechanisms involved in the thermogenic response of brown adipose tissue (BAT) to sympathetic nervous stimulation (e.g., by cold exposure) and to norepinephrine (NE) release are investigated. Three effects appear to play a role in the increased oxygen consumption (and heat production) of the adipocytes: increased membrane permeability, activation of the beta-adrenergic pathway, and enhancement of Na(+)/K(+) membrane pump activity. Increased passive influx of Na(+) and efflux of K(+) due to greater permeability raise the energy demands of the Na/K pump; the pump is also stimulated by increased cyclic AMP synthesis resulting from activation by NE of membrane-bound adenyl cyclase. Studies with inhibitors such as propanolol, phentolamine, and ouabain support this hypothesis.

The permeability evolution of tuffisites and outgassing from dense rhyolitic magma

NASA Astrophysics Data System (ADS)

Heap, M. J.; Tuffen, H.; Wadsworth, F. B.; Reuschlé, T.; Castro, J. M.; Schipper, C. I.

2017-12-01

Recent observations of rhyolitic lava effusion from eruptions in Chile indicate that simultaneous pyroclastic venting facilitates outgassing. Venting from conduit-plugging lava domes is pulsatory and occurs through shallow fracture networks that deliver pyroclastic debris and exsolved gases to the surface. However, these fractures become blocked as the particulate fracture infill sinters viscously, thus drastically reducing permeability. Tuffisites, fossilized debris-filled fractures of this venting process, are abundant in pyroclastic material ejected during hybrid explosive-effusive activity. Dense tuffisite-hosting obsidian bombs ejected from Volcán Chaitén (Chile) in 2008 afford an opportunity to better understand the permeability evolution of tuffisites within low-permeability conduit plugs, wherein gas mobility is reliant upon fracture pathways. We use laboratory measurements of the permeability and porosity of tuffisites that preserve different degrees of sintering, combined with a grainsize-based sintering model and constraints on pressure-time paths from H2O diffusion, to place first-order constraints on tuffisite permeability evolution. Inferred timescales of sintering-driven tuffisite compaction and permeability loss, spanning minutes to hours, coincide with observed vent pulsations during hybrid rhyolitic activity and, more broadly, timescales of pressurization accompanying silicic lava dome extrusion. We therefore conclude that sintering exerts a first-order control on fracture-assisted outgassing from low-permeability, conduit-plugging silicic magma.

Porosity, petrophysics and permeability of the Whitby Mudstone (UK)

NASA Astrophysics Data System (ADS)

Houben, M.; Barnhoorn, A.; Hardebol, N.; Ifada, M.; Boersma, Q.; Douma, L.; Peach, C. J.; Bertotti, G.; Drury, M. R.

2016-12-01

Typically pore diameters in shales range from the µm down to the nm scale and the effective permeability of shale reservoirs is a function of the interconnectivity between the pore space and the natural fracture network present. The length and spacing of mechanical induced and natural fractures is one of the factors controlling gas produtivity from unconventional reservoirs. Permeability of the Whitby Mudstone measured on 1 inch cores was linked to microstructure and combined with natural fracture spacing present in outcrops along the Yorkshire coast (UK) to get insight into possible fluid pathways from reservoir to well. We used a combination of different techniques to characterize the porosity (gas adsorption, Scanning Electron Microscopy), mineralogy (X-Ray Fluorescence, X-Ray Diffraction, Scanning Electron Microscopy) and permeability (pressure step decay) of the Whitby Mudstone. In addition, we mapped the natural fracture network as present in outcrops along the Yorkshire coast (UK) at the 10-2-101m scale. Mineralogically we are dealing with a rock that is high in clay content and has an average organic matter content of about 10%. Results show a low porosity (max. 7%) as well as low permeability for the Whitby Mudstone. The permeability, measured parallel to bedding, depends on the confining pressure and is 86 nanodarcy at 10 MPa effective confining pressure and decreases to 16 nanodarcy at 40 MPa effective confining pressure. At the scale of observation the average distance to nearest natural fracture is in the order of 0.13 meter and 90 percent of all matrix elements are spaced within 0.4 meter to the nearest fracture. By assuming darcy flow, a permeability of 100 nanodarcy and 10% of overpressure we calculated that for the Whitby mudstone most of the gas resides in the matrix for less than 60 days until it reaches the fracture network.

Mixed matrix membranes with fast and selective transport pathways for efficient CO2 separation

NASA Astrophysics Data System (ADS)

Hou, Jinpeng; Li, Xueqin; Guo, Ruili; Zhang, Jianshu; Wang, Zhongming

2018-03-01

To improve CO2 separation performance, porous carbon nanosheets (PCNs) were used as a filler into a Pebax MH 1657 (Pebax) matrix, fabricating mixed matrix membranes (MMMs). The PCNs exhibited a preferential horizontal orientation within the Pebax matrix because of the extremely large 2D plane and nanoscale thickness of the matrix. Therefore, the micropores of the PCNs provided fast CO2 transport pathways, which led to increased CO2 permeability. The reduced pore size of the PCNs was a consequence of the overlapping of PCNs and the polymer chains penetrating into the pores of the PCNs. The reduction in the pore size of the PCNs improved the CO2/gas selectivity. As a result, the CO2 permeability and CO2/CH4 selectivity of the Pebax membrane with 10 wt% PCNs-loading (Pebax-PCNs-10) were 520 barrer and 51, respectively, for CO2/CH4 mixed-gas. The CO2 permeability and CO2/N2 selectivity of the Pebax-PCNs-10 membrane were 614 barrer and 61, respectively, for CO2/N2 mixed-gas.

Single-walled carbon nanotube, multi-walled carbon nanotube and Fe2O3 nanoparticles induced mitochondria mediated apoptosis in melanoma cells.

PubMed

Naserzadeh, Parvaneh; Ansari Esfeh, Fatemeh; Kaviani, Mahboubeh; Ashtari, Khadijeh; Kheirbakhsh, Raheleh; Salimi, Ahmad; Pourahmad, Jalal

2018-06-01

Nanomaterials (NM) exhibit novel anticancer properties. The toxicity of three nanoparticles that are currently being produced in high tonnage including single-walled carbon nanotube (SWCNT), multi-walled carbon nanotube (MWCNT) and Fe 2 O 3 nanoparticles, were compared with normal and melanoma cells. All tested nanoparticles induced selective toxicity and caspase 3 activation through mitochondria pathway in melanoma cells and mitochondria cause the generating of reactive oxygen species (ROS), mitochondrial membrane potential decline (MMP collapse), mitochondria swelling, and cytochrome c release. The pretreatment of butylated hydroxytoluene (BHT), a cell-permeable antioxidant and cyclosporine A (Cs. A), a mitochondrial permeability transition (MPT), pore sealing agent decreased cytotoxicity, caspase 3 activation, ROS generation, and mitochondrial damages induced by SWCNT, MWCNT, and IONPs. Our promising results provide a potential approach for the future therapeutic use of SWCNT, MWCNT, and IONPs in melanoma through mitochondrial targeting.

Intranasal delivery of cyclobenzaprine hydrochloride-loaded thiolated chitosan nanoparticles for pain relief.

PubMed

Patel, Deepa; Naik, Sachin; Chuttani, Krishna; Mathur, Rashi; Mishra, Anil K; Misra, Ambikanandan

2013-09-01

The purpose of present investigation was to formulate and characterize the cyclobenzaprine HCl (CBZ)-loaded thiolated chitosan nanoparticles and assessment of in-vitro cell viability, trans-mucosal permeability on RPMI2650 cell monolayer, in-vivo pharmacokinetic and pharmacodynamic study of thiolated chitosan nanoparticles on Swiss albino mice after intranasal administration. A significant high permeation of drug was observed from thiolated chitosan nanoparticles with less toxicity on nasal epithelial cells. Brain uptake of the drug after (99m)Tc labeling was significantly enhanced after thiolation of chitosan. CBZ-loaded thiolated chitosan NPs significantly reverse the N-Methyl-.-Aspartate (NMDA)-induced hyperalgesia by intranasal administration than the CBZ solution. The studies of present investigation revealed that thiolation of chitosan significantly reduce trans-mucosal toxicity with enhanced trans-mucosal permeability via paracellular pathway and brain uptake of a hydrophilic drug (normally impermeable across blood brain barrier) and pain alleviation activity via intranasal route.

System dynamics of subcellular transport.

PubMed

Chen, Vivien Y; Khersonsky, Sonya M; Shedden, Kerby; Chang, Young Tae; Rosania, Gus R

2004-01-01

In pharmacokinetic experiments, interpretations often hinge on treating cells as a "black box": a single, lumped compartment or boundary. Here, a combinatorial library of fluorescent small molecules was used to visualize subcellular transport pathways in living cells, using a kinetic, high content imaging system to monitor spatiotemporal variations of intracellular probe distribution. Most probes accumulate in cytoplasmic vesicles and probe kinetics conform to a nested, two-compartment dynamical system. At steady state, probes preferentially partition from the extracellular medium to the cytosol, and from the cytosol to cytoplasmic vesicles, with hydrophobic molecules favoring sequestration. Altogether, these results point to a general organizing principle underlying the system dynamics of subcellular, small molecule transport. In addition to plasma membrane permeability, subcellular transport phenomena can determine the active concentration of small molecules in the cytosol and the efflux of small molecules from cells. Fundamentally, direct observation of intracellular probe distribution challenges the simple boundary model of classical pharmacokinetics, which considers cells as static permeability barriers.

Assessment of Regional Variation in Streamflow Responses ...

EPA Pesticide Factsheets

Aquatic ecosystems are sensitive to the modification of hydrologic regimes, experiencing declines in stream health as the streamflow regime is altered during urbanization. This study uses streamflow records to quantify the type and magnitude of hydrologic changes across urbanization gradients in nine U.S. cities (Atlanta, GA, Baltimore, MD, Boston, MA, Detroit, MI, Raleigh, NC, St. Paul, MN, Pittsburgh, PA, Phoenix, AZ, and Portland, OR) in two physiographic settings. Results indicate similar development trajectories among urbanization gradients, but heterogeneity in the type and magnitude of hydrologic responses to this apparently uniform urban pattern. Similar urban patterns did not confer similar hydrologic function. Study watersheds in landscapes with level slopes and high soil permeability had less frequent high-flow events, longer high-flow durations, lower flashiness response, and lower flow maxima compared to similarly developed watersheds in landscape with steep slopes and low soil permeability. Our results suggest that physical characteristics associated with level topography and high water-storage capacity buffer the severity of hydrologic changes associated with urbanization. Urbanization overlain upon a diverse set of physical templates creates multiple pathways toward hydrologic impairment; therefore, we caution against the use of the urban homogenization framework in examining geophysically dominated processes. This paper shows cities how to utili

Assessment of regional variation in streamflow responses to urbanization and the persistence of physiography.

PubMed

Hopkins, Kristina G; Morse, Nathaniel B; Bain, Daniel J; Bettez, Neil D; Grimm, Nancy B; Morse, Jennifer L; Palta, Monica M; Shuster, William D; Bratt, Anika R; Suchy, Amanda K

2015-03-03

Aquatic ecosystems are sensitive to the modification of hydrologic regimes, experiencing declines in stream health as the streamflow regime is altered during urbanization. This study uses streamflow records to quantify the type and magnitude of hydrologic changes across urbanization gradients in nine U.S. cities (Atlanta, GA, Baltimore, MD, Boston, MA, Detroit, MI, Raleigh, NC, St. Paul, MN, Pittsburgh, PA, Phoenix, AZ, and Portland, OR) in two physiographic settings. Results indicate similar development trajectories among urbanization gradients, but heterogeneity in the type and magnitude of hydrologic responses to this apparently uniform urban pattern. Similar urban patterns did not confer similar hydrologic function. Study watersheds in landscapes with level slopes and high soil permeability had less frequent high-flow events, longer high-flow durations, lower flashiness response, and lower flow maxima compared to similarly developed watersheds in landscape with steep slopes and low soil permeability. Our results suggest that physical characteristics associated with level topography and high water-storage capacity buffer the severity of hydrologic changes associated with urbanization. Urbanization overlain upon a diverse set of physical templates creates multiple pathways toward hydrologic impairment; therefore, we caution against the use of the urban homogenization framework in examining geophysically dominated processes.

Modeling stress/strain-dependent permeability changes for deep geoenergy applications

NASA Astrophysics Data System (ADS)

Rinaldi, Antonio Pio; Rutqvist, Jonny

2016-04-01

Rock permeability is a key parameter in deep geoenergy systems. Stress and strain changes induced at depth by fluid injection or extraction may substantially alter the rock permeability in an irreversible way. With regard to the geoenergies, some applications require the permeability to be enhanced to improve productivity. The rock permeability is generally enhanced by shearing process of faults and fractures (e.g. hydroshearing for Enhanced and Deep Geothermal Systems), or the creation of new fractures (e.g. hydrofracturing for shale gas). However, such processes may, at the same time, produce seismicity that can be felt by the local population. Moreover, the increased permeability due to fault reactivation may pose at risk the sealing capacity of a storage site (e.g. carbon sequestration or nuclear waste disposal), providing then a preferential pathway for the stored fluids to escape at shallow depth. In this work we present a review of some recent applications aimed at understanding the coupling between stress (or strain) and permeability. Examples of geoenergy applications include both EGS and CO2 sequestration. To investigate both "wanted" and "unwanted" effects, THM simulations have been carried out with the TOUGH-FLAC simulator. Our studies include constitutive equations relating the permeability to mean effective stress, effective normal stress, volumetric strain, as well as accounting for permeability variation as related to fault/fracture reactivation. Results show that the geomechanical effects have a large role in changing the permeability, hence affecting fluids leakage, reservoir enhancement, as well as the induced seismicity.

Evaporite Caprock Integrity. An experimental study of reactive mineralogy and pore-scale heterogeneity during brine-CO 2 exposure

DOE PAGES

Smith, Megan M.; Sholokhova, Yelena; Hao, Yue; ...

2012-07-25

Characterization and geochemical data are presented from a core-flooding experiment on a sample from the Three Fingers evaporite unit forming the lower extent of caprock at the Weyburn-Midale reservoir, Canada. This low-permeability sample was characterized in detail using X-ray computed microtomography before and after exposure to CO 2-acidified brine, allowing mineral phase and voidspace distributions to be quantified in three dimensions. Solution chemistry indicated that CO 2-acidified brine preferentially dissolved dolomite until saturation was attained, while anhydrite remained unreactive. Dolomite dissolution contributed to increases in bulk permeability through the formation of a localized channel, guided by microfractures as well asmore » porosity and reactive phase distributions aligned with depositional bedding. An indirect effect of carbonate mineral reactivity with CO 2-acidified solution is voidspace generation through physical transport of anhydrite freed from the rock matrix following dissolution of dolomite. The development of high permeability fast pathways in this experiment highlights the role of carbonate content and potential fracture orientations in evaporite caprock formations considered for both geologic carbon sequestration and CO 2-enhanced oil recovery operations.« less

The Influence of Multi-Scale Stratal Architecture on Multi-Phase Flow

NASA Astrophysics Data System (ADS)

Soltanian, M.; Gershenzon, N. I.; Ritzi, R. W.; Dominic, D.; Ramanathan, R.

2012-12-01

Geological heterogeneity affects flow and transport in porous media, including the migration and entrapment patterns of oil, and efforts for enhanced oil recovery. Such effects are only understood through their relation to a hierarchy of reservoir heterogeneities over a range of scales. Recent work on modern rivers and ancient sediments has led to a conceptual model of the hierarchy of fluvial forms within channel-belts of gravelly braided rivers, and a quantitative model for the corresponding scales of heterogeneity within the stratal architecture (e.g. [Lunt et al (2004) Sedimentology, 51 (3), 377]). In related work, a three-dimensional digital model was developed which represents these scales of fluvial architecture, the associated spatial distribution of permeability, and the connectivity of high-permeability pathways across the different scales of the stratal hierarchy [Ramanathan et al, (2010) Water Resour. Res., 46, W04515; Guin et al, (2010) Water Resour. Res., 46, W04516]. In the present work we numerically examine three-phase fluid flow (water-oil-gas) incorporating the multi-scale model for reservoir heterogeneity spanning the scales from 10^-1 to 10^3 meters. Comparison with results of flow in a reservoir with homogeneous permeability is made showing essentially different flow dynamics.

The role of apoptosis in LDL transport through cultured endothelial cell monolayers

PubMed Central

Cancel, Limary M.; Tarbell, John M.

2009-01-01

We have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for LDL transport under convective conditions, accounting for more than 90% of the transport [1]. To explore the role of apoptosis in the leaky junction pathway, TNFα and cycloheximide (TNFα/CHX) were used to induce an elevated rate of apoptosis in cultured bovine aortic endothelial cell (BAEC) monolayers and the convective fluxes of LDL and water were measured. Treatment with TNFα/CHX induced a 18.3-fold increase in apoptosis and a 4.4-fold increase in LDL permeability. Increases in apoptosis and permeability were attenuated by treatment with the caspase inhibitor Z-VAD-FMK. Water flux increased by 2.7-fold after treatment with TNFα/CHX, and this increase was not attenuated by treatment with Z-VAD-FMK. Immunostaining of the tight junction protein ZO-1 showed that TNFα/CHX treatment disrupts the tight junction in addition to inducing apoptosis. This disruption is present even when Z-VAD-FMK is used to inhibit apoptosis, and likely accounts for the increase in water flux. We found a strong correlation between the rate of apoptosis and the permeability of BAEC monolayers to LDL. These results demonstrate the potential of manipulating endothelial monolayer permeability by altering the rate of apoptosis pharmacollogicaly. This has implications for the treatment of atherosclerosis. PMID:19709659

Fracture and compaction of andesite in a volcanic edifice.

PubMed

Heap, M J; Farquharson, J I; Baud, P; Lavallée, Y; Reuschlé, T

The failure mode of lava-dilatant or compactant-depends on the physical attributes of the lava, primarily the porosity and pore size, and the conditions under which it deforms. The failure mode for edifice host rock has attendant implications for the structural stability of the edifice and the efficiency of the sidewall outgassing of the volcanic conduit. In this contribution, we present a systematic experimental study on the failure mode of edifice-forming andesitic rocks (porosity from 7 to 25 %) from Volcán de Colima, Mexico. The experiments show that, at shallow depths (<1 km), both low- and high-porosity lavas dilate and fail by shear fracturing. However, deeper in the edifice (>1 km), while low-porosity (<10 %) lava remains dilatant, the failure of high-porosity lava is compactant and driven by cataclastic pore collapse. Although inelastic compaction is typically characterised by the absence of strain localisation, we observe compactive localisation features in our porous andesite lavas manifest as subplanar surfaces of collapsed pores. In terms of volcano stability, faulting in the upper edifice could destabilise the volcano, leading to an increased risk of flank or large-scale dome collapse, while compactant deformation deeper in the edifice may emerge as a viable mechanism driving volcano subsidence, spreading and destabilisation. The failure mode influences the evolution of rock physical properties: permeability measurements demonstrate that a throughgoing tensile fracture increases sample permeability (i.e. equivalent permeability) by about a factor of two, and that inelastic compaction to an axial strain of 4.5 % reduces sample permeability by an order of magnitude. The implication of these data is that sidewall outgassing may therefore be efficient in the shallow edifice, where rock can fracture, but may be impeded deeper in the edifice due to compaction. The explosive potential of a volcano may therefore be subject to increase over time if the progressive compaction and permeability reduction in the lower edifice cannot be offset by the formation of permeable fracture pathways in the upper edifice. The mode of failure of the edifice host rock is therefore likely to be an important factor controlling lateral outgassing and thus eruption style (effusive versus explosive) at stratovolcanoes.

Characterization of Preferential Flow Path in Fractured Rock Using Heat-pulse Flowmeter

NASA Astrophysics Data System (ADS)

Lee, Tsai-Ping; Lin, Ming-Hsuan; Chuang, Po-Yu; Chia, Yeeping

2015-04-01

Rigorous thinking on how to dispose radioactive wastes safely is essential to mankind and living environment. The concepts of multiple barriers and deep geologic disposal remain the preferred option to retard the radionuclide migration in most countries. However, the investigation of preferential groundwater flow path in a fractured rock is a challenge to the characterization of potential disposal site. Heat-pulse flowmeter is a developing logging tool for measuring the vertical flow velocity in a borehole under a constant pumping or injection rate and provides a promising direct measurement method for determining the vertical distribution of hydraulic conductivity of formation. As heat-pulse flowmeter is a potential technique to measure low-velocity borehole flow, we adopted it to test the feasibility of detecting permeable fractures. Besides, a new magnetic tracer made by nano-iron particles is developed to identify the possible flow path precisely and to verify the permeable section detected by the heat-pulse flowmeter. The magnetic tracer was received by a magnet array and can also be detected by a sensor of electric conductivity. The test site is located in the Heshe of Taiwan. Eight wells were established in a fractured sandy siltstone for characterizing the fracture network. The test wells are 25 to 45 m depth and opened ranging from 15 to 45 m. Prior to the heat-pulse flowmeter measurement, we also performed surface geological investigation, pumping test, geophysical logging, and salt tracer test. Field measurements using heat-pulse flowmeter were then conducted at a constant pumping rate. The measurement interval is 50 to 100 cm in depth but improved to 25 cm near the relatively permeable zone. Based on the results of heat-pulse flowmeter, several permeable sections were identified. The magnetic tracer tests were then conducted to verify the potential preferential flow pathway between adjacent wells. Test results indicated that water flow in borehole is produced primarily from a few fractures. However, the large aperture and high density of fractures did not certainly correlate well to the permeable section. Integration of heat-pulse flowmeter measurement with other in-situ tests, it is possible to identify the exact location of the highly permeable fractures.

Cholecystokinin induces caspase activation and mitochondrial dysfunction in pancreatic acinar cells. Roles in cell injury processes of pancreatitis.

PubMed

Gukovskaya, Anna S; Gukovsky, Ilya; Jung, Yoon; Mouria, Michelle; Pandol, Stephen J

2002-06-21

Apoptosis and necrosis are critical parameters of pancreatitis, the mechanisms of which remain unknown. Many characteristics of pancreatitis can be studied in vitro in pancreatic acini treated with high doses of cholecystokinin (CCK). We show here that CCK stimulates apoptosis and death signaling pathways in rat pancreatic acinar cells, including caspase activation, cytochrome c release, and mitochondrial depolarization. The mitochondrial dysfunction is mediated by upstream caspases (possibly caspase-8) and, in turn, leads to activation of caspase-3. CCK causes mitochondrial alterations through both permeability transition pore-dependent (cytochrome c release) and permeability transition pore-independent (mitochondrial depolarization) mechanisms. Caspase activation and mitochondrial alterations also occur in untreated pancreatic acinar cells; however, the underlying mechanisms are different. In particular, caspases protect untreated acinar cells from mitochondrial damage. We found that caspases not only mediate apoptosis but also regulate other parameters of CCK-induced acinar cell injury that are characteristic of pancreatitis; in particular, caspases negatively regulate necrosis and trypsin activation in acinar cells. The results suggest that the observed signaling pathways regulate parenchymal cell injury and death in CCK-induced pancreatitis. Protection against necrosis and trypsin activation by caspases can explain why the severity of pancreatitis in experimental models correlates inversely with the extent of apoptosis.

Living with death: The evolution of the mitochondrial pathway of apoptosis in animals

PubMed Central

Oberst, Andrew; Bender, Cheryl; Green, Douglas R.

2008-01-01

The mitochondrial pathway of cell death, in which apoptosis proceeds following mitochondrial outer membrane permeablization (MOMP), release of cytochrome c, and APAF-1 apoptosome-mediated caspase activation, represents the major pathway of physiological apoptosis in vertebrates. However, the well-characterized apoptotic pathways of the invertebrates C. elegans and D. melanogaster indicate that this apoptotic pathway is not universally conserved among animals. This review will compare the role of the mitochondria in the apoptotic programs of mammals, nematodes, and flies, and will survey our knowledge of the apoptotic pathways of other, less familiar model organisms in an effort to explore the evolutionary origins of the mitochondrial pathway of apoptosis. PMID:18451868

Molecular pathways of pannexin1-mediated neurotoxicity

PubMed Central

Shestopalov, Valery I.; Slepak, Vladlen Z.

2014-01-01

Pannexin1 (Panx1) forms non-selective membrane channels, structurally similar to gap junction hemichannels, and are permeable to ions, nucleotides, and other small molecules below 900 Da. Panx1 activity has been implicated in paracrine signaling and inflammasome regulation. Recent studies in different animal models showed that overactivation of Panx1 correlates with a selective demise of several types of neurons, including retinal ganglion cells, brain pyramidal, and enteric neurons. The list of Panx1 activators includes extracellular ATP, glutamate, high K+, Zn2+, fibroblast growth factors (FGFs),pro-inflammatory cytokines, and elevation of intracellular Ca2+. Most of these molecules are released following mechanical, ischemic, or inflammatory injury of the CNS, and rapidly activate the Panx1 channel. Prolonged opening of Panx1 channel induced by these “danger signals” triggers a cascade of neurotoxic events capable of killing cells. The most vulnerable cell type are neurons that express high levels of Panx1. Experimental evidence suggests that Panx1 channels mediate at least two distinct neurotoxic processes: increased permeability of the plasma membrane and activation of the inflammasome in neurons and glia. Importantly, both pharmacological and genetic inactivation of Panx1 suppresses both these processes, providing a marked protection in several disease and injury models. These findings indicate that external danger signals generated after diverse types of injuries converge to activate Panx1. In this review we discuss molecular mechanisms associated with Panx1 toxicity and the crosstalk between different pathways. PMID:24575045

Lithological and hydrological influences on ground-water composition in a heterogeneous carbonate-clay aquifer system

USGS Publications Warehouse

Kauffman, S.J.; Herman, J.S.; Jones, B.F.

1998-01-01

The influence of clay units on ground-water composition was investigated in a heterogeneous carbonate aquifer system of Miocene age in southwest Florida, known as the Intermediate aquifer system. Regionally, the ground water is recharged inland, flows laterally and to greater depths in the aquifer systems, and is discharged vertically upward at the saltwater interface along the coast. A depth profile of water composition was obtained by sampling ground water from discrete intervals within the permeable carbonate units during coring and by squeezing pore water from a core of the less-permeable clay layers. A normative salt analysis of solute compositions in the water indicated a marine origin for both types of water and an evolutionary pathway for the clay water that involves clay diagenesis. The chemical composition of the ground water in the carbonate bedrock is significantly different from that of the pore water in the clay layers. Dissolution of clays and opaline silica results in high silica concentrations relative to water in other parts of the Intermediate aquifer system. Water enriched in chloride relative to the overlying and underlying ground water recharges the aquifer inland where the confining clay layer is absent, and it dissolves carbonate and silicate minerals and reacts with clays along its flow path, eventually reaching this coastal site and resulting in the high chloride and silica concentrations observed in the middle part of the Intermediate aquifer system. Reaction-path modeling suggests that the recharging surficial water mixes with sulfate-rich water upwelling from the Upper Floridan aquifer, and carbonate mineral dissolution and precipitation, weathering and exchange reactions, clay mineral diagenesis, clay and silica dissolution, organic carbon oxidation, and iron and sulfate reduction result in the observed water compositions.A study was conducted to clarify the influence of clay units on ground-water composition in a heterogeneous carbonate aquifer system of Miocene age in southwest Florida. A depth profile of water composition was obtained by sampling ground water from discrete intervals within the permeable carbonate units during coring and by squeezing pore water from a core of the less-permeable clay layers. A normative salt analysis of solute compositions in the water indicated a marine origin for both types of water and an evolutionary pathway for the clay water that involves clay diagenesis. The factors influencing water compositions were determined.

Planetesimal core formation with partial silicate melting using in-situ high P, high T, deformation x-ray microtomography

NASA Astrophysics Data System (ADS)

Anzures, B. A.; Watson, H. C.; Yu, T.; Wang, Y.

2017-12-01

Differentiation is a defining moment in formation of terrestrial planets and asteroids. Smaller planetesimals likely didn't reach high enough temperatures for widescale melting. However, we infer that core formation must have occurred within a few million years from Hf-W dating. In lieu of a global magma ocean, planetesimals likely formed through inefficient percolation. Here, we used in-situ high temperature, high pressure, x-ray microtomography to track the 3-D evolution of the sample at mantle conditions as it underwent shear deformation. Lattice-Boltzmann simulations for permeability were used to characterize the efficiency of melt percolation. Mixtures of KLB1 peridotite plus 6.0 to 12.0 vol% FeS were pre-sintered to achieve an initial equilibrium microstructure, and then imaged through several consecutive cycles of heating and deformation. The maximum calculated melt segregation velocity was found to be 0.37 cm/yr for 6 vol.% FeS and 0.61 cm/year for 12 vol.% FeS, both below the minimum velocity of 3.3 cm/year required for a 100km planetesimal to fully differentiate within 3 million years. However, permeability is also a function of grain size and thus the samples having smaller grains than predicted for small planetesimals could have contributed to low permeability and also low migration velocity. The two-phase (sulfide melt and silicate melt) flow at higher melt fractions (6 vol.% and 12 vol.% FeS) was an extension of a similar study1 containing only sulfide melt at lower melt fraction (4.5 vol.% FeS). Contrary to the previous study, deformation did result in increased permeability until the sample was sheared by twisting the opposing Drickamer anvils by 360 degrees. Also, the presence of silicate melt caused the FeS melt to coalesce into less connected pathways as the experiment with 6 vol.% FeS was found to be less permeable than the one with 4.5 vol.% FeS but without any partial melt. The preliminary data from this study suggests that impacts as well as higher temperature leading to partial melting of the silicate portion of the mantle could have contributed to fast enough core formation. 1. Todd, K.A., Watson, H.C., Yu, T., Wang, Y., American Mineralogist, 101.9, 1996-2004, 2016

Targeted Control of Permeability Using Carbonate Dissolution/Precipitation Reactions

NASA Astrophysics Data System (ADS)

Clarens, A. F.; Tao, Z.; Plattenberger, D.

2016-12-01

Targeted mineral precipitation reactions are a promising approach for controlling fluid flow in the deep subsurface. Here we studied the potential to use calcium and magnesium bearing silicates as cation donors that would react with aqueous phase CO2 under reservoir conditions to form solid carbonate precipitates. Preliminary experiments in high pressure and temperature columns suggest that these reactions can effectively lower the permeability of a porous media. Wollastonite (CaSiO3) was used as the model silicate, injected as solid particles into the pore space of a packed column, which was then subsequently flooded with CO2(aq). The reactions occur spontaneously, leveraging the favorable kinetics that occur at the high temperature and pressure conditions characteristic of the deep subsurface, to form solid phase calcium carbonate (CaCO3) and amorphous silica (SiO2) within the pore space. Both x-ray tomography imaging of reacted columns and electron microscopy imaging of thin sections were used to characterize where dissolution/precipitation occurred within the porous media. The spatial distribution of the products was closely tied to the flow rate and the duration of the experiment. The SiO2 product precipitated in close spatial proximity to the CaSiO3 reactant. The CaCO3 product, which is sensitive to the low pH and high pCO2 brine, precipitated out of solution further down the column as Ca2+ ions moved with the brine. The permeability of the columns decreased by several orders of magnitude after injecting the CaSiO3 particles. Following carbonation, the permeability decreased even further as precipitates filled flow paths within the pore network. A pore network model was developed to help understand the interplay between precipitation kinetics and flow in altering the permeability of the porous media. The effect of particle concentration and size, pore size, reaction time, and pCO2, are explored on pore/fracture aperture and reaction extent. To provide better control of these dynamics and ultimately devise a mechanism to deliver carbonation seed particles into leakage pathways, we are exploring the potential to functionalize the silicate particles using temperature sensitive polymer coatings.

Mitochondrial Ca2+ influx and efflux rates in guinea pig cardiac mitochondria: low and high affinity effects of cyclosporine A.

PubMed

Wei, An-Chi; Liu, Ting; Cortassa, Sonia; Winslow, Raimond L; O'Rourke, Brian

2011-07-01

Ca(2+) plays a central role in energy supply and demand matching in cardiomyocytes by transmitting changes in excitation-contraction coupling to mitochondrial oxidative phosphorylation. Matrix Ca(2+) is controlled primarily by the mitochondrial Ca(2+) uniporter and the mitochondrial Na(+)/Ca(2+) exchanger, influencing NADH production through Ca(2+)-sensitive dehydrogenases in the Krebs cycle. In addition to the well-accepted role of the Ca(2+)-triggered mitochondrial permeability transition pore in cell death, it has been proposed that the permeability transition pore might also contribute to physiological mitochondrial Ca(2+) release. Here we selectively measure Ca(2+) influx rate through the mitochondrial Ca(2+) uniporter and Ca(2+) efflux rates through Na(+)-dependent and Na(+)-independent pathways in isolated guinea pig heart mitochondria in the presence or absence of inhibitors of mitochondrial Na(+)/Ca(2+) exchanger (CGP 37157) or the permeability transition pore (cyclosporine A). cyclosporine A suppressed the negative bioenergetic consequences (ΔΨ(m) loss, Ca(2+) release, NADH oxidation, swelling) of high extramitochondrial Ca(2+) additions, allowing mitochondria to tolerate total mitochondrial Ca(2+) loads of >400nmol/mg protein. For Ca(2+) pulses up to 15μM, Na(+)-independent Ca(2+) efflux through the permeability transition pore accounted for ~5% of the total Ca(2+) efflux rate compared to that mediated by the mitochondrial Na(+)/Ca(2+) exchanger (in 5mM Na(+)). Unexpectedly, we also observed that cyclosporine A inhibited mitochondrial Na(+)/Ca(2+) exchanger-mediated Ca(2+) efflux at higher concentrations (IC(50)=2μM) than those required to inhibit the permeability transition pore, with a maximal inhibition of ~40% at 10μM cyclosporine A, while having no effect on the mitochondrial Ca(2+) uniporter. The results suggest a possible alternative mechanism by which cyclosporine A could affect mitochondrial Ca(2+) load in cardiomyocytes, potentially explaining the paradoxical toxic effects of cyclosporine A at high concentrations. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. Copyright © 2011 Elsevier B.V. All rights reserved.

Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS).

PubMed

Alvarez-Figueroa, M Javiera; Pessoa-Mahana, C David; Palavecino-González, M Elisa; Mella-Raipán, Jaime; Espinosa-Bustos, Cristián; Lagos-Muñoz, Manuel E

2011-06-01

The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P(oct) value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).

Caprock integrity susceptibility to permeable fracture creation

DOE PAGES

Frash, Luke; Carey, James William; Ickes, Timothy Lee; ...

2017-07-14

Caprock leakage is of crucial concern for environmentally and economically sustainable development of carbon dioxide sequestration and utilization operations. One potential leakage pathway is through fractures or faults that penetrate the caprock. In this study, we investigate the permeability induced by fracturing initially intact Marcellus shale outcrop specimens at stressed conditions using a triaxial direct-shear method. Measurements of induced permeability, fracture geometry, displacement, and applied stresses were all obtained at stressed conditions to investigate the coupled processes of fracturing and fluid flow as may occur in the subsurface. Fracture geometry was directly observed at stressed conditions using X-ray radiography video.more » Numerical simulation was performed to evaluate the stress distribution developed in the experiments. Our experiments show that permeability induced by fracturing is strongly dependent on the stresses at which the fractures are created, the magnitude of shearing displacement, and the duration of flow. The strongest permeability contrast was observed when comparing specimens fractured at low stress to others fractured at higher stress. Measureable fracture permeability decreased by up to 7 orders of magnitude over a corresponding triaxial confining stress range of 3.5 MPa to 30 MPa. These results show that increasing stress, depth, and time are all significant permeability inhibitors that may limit potential leakage through fractured caprock.« less

Caprock integrity susceptibility to permeable fracture creation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frash, Luke; Carey, James William; Ickes, Timothy Lee

Caprock leakage is of crucial concern for environmentally and economically sustainable development of carbon dioxide sequestration and utilization operations. One potential leakage pathway is through fractures or faults that penetrate the caprock. In this study, we investigate the permeability induced by fracturing initially intact Marcellus shale outcrop specimens at stressed conditions using a triaxial direct-shear method. Measurements of induced permeability, fracture geometry, displacement, and applied stresses were all obtained at stressed conditions to investigate the coupled processes of fracturing and fluid flow as may occur in the subsurface. Fracture geometry was directly observed at stressed conditions using X-ray radiography video.more » Numerical simulation was performed to evaluate the stress distribution developed in the experiments. Our experiments show that permeability induced by fracturing is strongly dependent on the stresses at which the fractures are created, the magnitude of shearing displacement, and the duration of flow. The strongest permeability contrast was observed when comparing specimens fractured at low stress to others fractured at higher stress. Measureable fracture permeability decreased by up to 7 orders of magnitude over a corresponding triaxial confining stress range of 3.5 MPa to 30 MPa. These results show that increasing stress, depth, and time are all significant permeability inhibitors that may limit potential leakage through fractured caprock.« less

Heparanase-driven inflammation from the AGEs-stimulated macrophages changes the functions of glomerular endothelial cells.

PubMed

Xu, Guang; Qin, Qiaojing; Yang, Min; Qiao, Zhongdong; Gu, Yong; Niu, Jianying

2017-02-01

Amounts of macrophages were infiltrated in glomeruli in diabetic nephropathy. Heparanase has been thought to be closely related to proteinuria. Our aims were to determine the effect of heparanase on the inflammation in AGEs-stimulated macrophages and its role on the functions of glomerular endothelial cells (GEnCs). The expression of inflammation cytokines in macrophages were assayed by q-RT PCR, western, and ELISA. Then western was used to measure the expression of RAGE and key proteins in NF-κB pathway in macrophages. The expression of the adherence molecules and tight junction proteins in GEnCs were assessed by western. The adherence of mononuclear cells to GEnCs were observed by HE staining and transendothelial FITC-BSA were tested for the permeability of GEnCs. HPA siRNA and heparanase inhibitor sulodexide could attenuate the increasing inflammatory factors (TNF-α and IL-1β) in AGEs-stimulated macrophages. NF-κB inhibitor PDTC could also decrease the augmented inflammation cytokines through inhibiting the activation of the NF-κB pathway induced by AGEs. The phosphorylation of NF-κB signaling pathway could be also attenuated by HPA siRNA and sulodexide, the same to the receptor of AGEs RAGE. When the macrophage-conditioned culture medium were added to the glomerular endothelial cells, we found HPA siRNA and sulodexide groups could decrease the increasing adherence and permeability of GEnCs induced by AGEs. Heparanase increases the inflammation in AGEs-stimulated macrophages through activating the RAGE-NF-κB pathway. Heparanase driven inflammation from AGEs-stimulated macrophages increases the adherence of GEnCs and augments the permeability of GEnCs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Structure-Based Design of Highly Selective Inhibitors of the CREB Binding Protein Bromodomain.

PubMed

Denny, R Aldrin; Flick, Andrew C; Coe, Jotham; Langille, Jonathan; Basak, Arindrajit; Liu, Shenping; Stock, Ingrid; Sahasrabudhe, Parag; Bonin, Paul; Hay, Duncan A; Brennan, Paul E; Pletcher, Mathew; Jones, Lyn H; Chekler, Eugene L Piatnitski

2017-07-13

Chemical probes are required for preclinical target validation to interrogate novel biological targets and pathways. Selective inhibitors of the CREB binding protein (CREBBP)/EP300 bromodomains are required to facilitate the elucidation of biology associated with these important epigenetic targets. Medicinal chemistry optimization that paid particular attention to physiochemical properties delivered chemical probes with desirable potency, selectivity, and permeability attributes. An important feature of the optimization process was the successful application of rational structure-based drug design to address bromodomain selectivity issues (particularly against the structurally related BRD4 protein).

Role of lipids in the formation and maintenance of the cutaneous permeability barrier.

PubMed

Feingold, Kenneth R; Elias, Peter M

2014-03-01

The major function of the skin is to form a barrier between the internal milieu and the hostile external environment. A permeability barrier that prevents the loss of water and electrolytes is essential for life on land. The permeability barrier is mediated primarily by lipid enriched lamellar membranes that are localized to the extracellular spaces of the stratum corneum. These lipid enriched membranes have a unique structure and contain approximately 50% ceramides, 25% cholesterol, and 15% free fatty acids with very little phospholipid. Lamellar bodies, which are formed during the differentiation of keratinocytes, play a key role in delivering the lipids from the stratum granulosum cells into the extracellular spaces of the stratum corneum. Lamellar bodies contain predominantly glucosylceramides, phospholipids, and cholesterol and following the exocytosis of lamellar lipids into the extracellular space of the stratum corneum these precursor lipids are converted by beta glucocerebrosidase and phospholipases into the ceramides and fatty acids, which comprise the lamellar membranes. The lipids required for lamellar body formation are derived from de novo synthesis by keratinocytes and from extra-cutaneous sources. The lipid synthetic pathways and the regulation of these pathways are described in this review. In addition, the pathways for the uptake of extra-cutaneous lipids into keratinocytes are discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. Published by Elsevier B.V.

Transepithelial transport of biperiden hydrochloride in Caco-2 cell monolayers.

PubMed

Abalos, Ivana S; Rodríguez, Yanina I; Lozano, Verónica; Cereseto, Marina; Mussini, Maria V; Spinetto, Marta E; Chiale, Carlos; Pesce, Guido

2012-09-01

The aim of this research has been to determine the biperiden hydrochloride permeability in Caco-2 model, in order to classify it based on the Biopharmaceutics Classification System (BCS). The World Health Organization (WHO) as well as many other authors have provisionally assigned the drug as BCS class I (high solubility-high permeability) or III (high solubility-low permeability), based on different methods. We determined biperiden BCS class by comparing its permeability to 5 pre-defined compounds: atenolol and ranitidine hydrochloride (low permeability group) and metoprolol tartrate, sodium naproxen and theophylline (high permeability group). Since biperiden permeability was higher than those obtained for high permeability drugs, we classified it as a BCS class I compound. On the other hand, as no differences were obtained for permeability values when apical to basolateral and basolateral to apical fluxes were studied, this drug cannot act as a substrate of efflux transporters. As a consequence of our results, we suggest that the widely used antiparkinsonian drug, biperiden, should be candidate for a waiver of in vivo bioequivalence studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Numerical studies on the performance of an aerosol respirator with faceseal leakage

NASA Astrophysics Data System (ADS)

Zaripov, S. K.; Mukhametzanov, I. T.; Grinshpun, S. A.

2016-11-01

We studied the efficiency of a facepiece filtering respirator (FFR) in presence of a measurable faceseal leakage using the previously developed model of a spherical sampler with porous layer. In our earlier study, the model was validated for a specific filter permeability value. In this follow-up study, we investigated the effect of permeability on the overall respirator performance accounting for the faceseal leakage. The Total Inward Leakage (TIL) was calculated as a function of the leakage-to-filter surface ratio and the particle diameter. A good correlation was found between the theoretical and experimental TIL values. The TIL value was shown to increase and the effect of particle size on TIL to decrease as the leakage-to- filter surface ratio grows. The model confirmed that within the most penetrating particle size range (∼50 nm) and at relatively low leakage-to-filter surface ratios, an FFR performs better (TIL is lower) when the filter has a lower permeability which should be anticipated as long as the flow through the filter represents the dominant particle penetration pathway. An increase in leak size causes the TIL to rise; furthermore, under certain leakage-to-filter surface ratios, TIL for ultrafine particles becomes essentially independent on the filter properties due to a greater contribution of the aerosol flow through the faceseal leakage. In contrast to the ultrafine fraction, the larger particles (e.g., 800 nm) entering a typical high- or medium-quality respirator filter are almost fully collected by the filter medium regardless of its permeability; at the same time, the fraction penetrated through the leakage appears to be permeability- dependent: higher permeability generally results in a lower pressure drop through the filter which increases the air flow through the filter at the expense of the leakage flow. The latter reduces the leakage effect thus improving the overall respiratory protection level. The findings of this study provide valuable information for developing new respirators with a predictable actual workplace protection factor.

The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization.

PubMed

Zhang, Feng; Prahst, Claudia; Mathivet, Thomas; Pibouin-Fragner, Laurence; Zhang, Jiasheng; Genet, Gael; Tong, Raymond; Dubrac, Alexandre; Eichmann, Anne

2016-11-24

Vascular permeability and neovascularization are implicated in many diseases including retinopathies and diabetic wound healing. Robo4 is an endothelial-specific transmembrane receptor that stabilizes the vasculature, as shown in Robo4 -/- mice that develop hyperpermeability, but how Robo4 signals remained unclear. Here we show that Robo4 deletion enhances permeability and revascularization in oxygen-induced retinopathy (OIR) and accelerates cutaneous wound healing. To determine Robo4 signalling pathways, we generated transgenic mice expressing a truncated Robo4 lacking the cytoplasmic domain (Robo4ΔCD). Robo4ΔCD expression is sufficient to prevent permeability, and inhibits OIR revascularization and wound healing in Robo4 -/- mice. Mechanistically, Robo4 does not affect Slit2 signalling, but Robo4 and Robo4ΔCD counteract Vegfr2-Y949 (Y951 in human VEGFR2) phosphorylation by signalling through the endothelial UNC5B receptor. We conclude that Robo4 inhibits angiogenesis and vessel permeability independently of its cytoplasmic domain, while activating VEGFR2-Y951 via ROBO4 inhibition might accelerate tissue revascularization in retinopathy of prematurity and in diabetic patients.

Characteristics and origin of the relatively high-quality tight reservoir in the Silurian Xiaoheba Formation in the southeastern Sichuan Basin

PubMed Central

Gong, Xiaoxing; Shi, Zejin; Wang, Yong; Tian, Yaming; Li, Wenjie; Liu, Lei

2017-01-01

A mature understanding of the sandstone gas reservoir in the Xiaoheba Formation in the southeastern Sichuan Basin remains lacking. To assess the reservoir characteristics and the origin of the high-quality reservoir in the Xiaoheba Formation, this paper uses systematic field investigations, physical property analysis, thin section identification, scanning electron microscopy and electron microprobe methods. The results indicate that the Xiaoheba sandstone is an ultra-tight and ultra-low permeability reservoir, with an average porosity of 2.97% and an average permeability of 0.56×10−3 μm2. This promising reservoir is mainly distributed in the Lengshuixi and Shuangliuba regions and the latter has a relatively high-quality reservoir with an average porosity of 5.28% and average permeability of 0.53×10−3 μm2. The reservoir space comprises secondary intergranular dissolved pores, moldic pores and fractures. Microfacies, feldspar dissolution and fracture connectivity control the quality of this reservoir. The relatively weak compaction and cementation in the interbedded delta front distal bar and interdistributary bay microfacies indirectly protected the primary intergranular pores and enhanced late-stage dissolution. Late-stage potassium feldspar dissolution was controlled by the early-stage organic acid dissolution intensity and the distance from the hydrocarbon generation center. Early-stage fractures acted as pathways for organic acid migration and were therefore important factors in the formation of the reservoir. Based on these observations, the area to the west of the Shuangliuba and Lengshuixi regions has potential for gas exploration. PMID:28686735

Claudin-4 is required for modulation of paracellular permeability by muscarinic acetylcholine receptor in epithelial cells.

PubMed

Cong, Xin; Zhang, Yan; Li, Jing; Mei, Mei; Ding, Chong; Xiang, Ruo-Lan; Zhang, Li-Wei; Wang, Yun; Wu, Li-Ling; Yu, Guang-Yan

2015-06-15

The epithelial cholinergic system plays an important role in water, ion and solute transport. Previous studies have shown that activation of muscarinic acetylcholine receptors (mAChRs) regulates paracellular transport of epithelial cells; however, the underlying mechanism is still largely unknown. Here, we found that mAChR activation by carbachol and cevimeline reduced the transepithelial electrical resistance (TER) and increased the permeability of paracellular tracers in rat salivary epithelial SMG-C6 cells. Carbachol induced downregulation and redistribution of claudin-4, but not occludin or ZO-1 (also known as TJP1). Small hairpin RNA (shRNA)-mediated claudin-4 knockdown suppressed, whereas claudin-4 overexpression retained, the TER response to carbachol. Mechanistically, the mAChR-modulated claudin-4 properties and paracellular permeability were triggered by claudin-4 phosphorylation through ERK1/2 (also known as MAPK3 and MAPK1, respectively). Mutagenesis assay demonstrated that S195, but not S199, S203 or S207, of claudin-4, was the target for carbachol. Subsequently, the phosphorylated claudin-4 interacted with β-arrestin2 and triggered claudin-4 internalization through the clathrin-dependent pathway. The internalized claudin-4 was further degraded by ubiquitylation. Taken together, these findings suggested that claudin-4 is required for mAChR-modulated paracellular permeability of epithelial cells through an ERK1/2, β-arrestin2, clathrin and ubiquitin-dependent signaling pathway. © 2015. Published by The Company of Biologists Ltd.

Evaluation of the permeability of agricultural films to various fumigants.

PubMed

Qian, Yaorong; Kamel, Alaa; Stafford, Charles; Nguyen, Thuy; Chism, William J; Dawson, Jeffrey; Smith, Charles W

2011-11-15

A variety of agricultural films are commercially available for managing emissions and enhancing pest control during soil fumigation. These films are manufactured using different materials and processes which can ultimately result in different permeability to fumigants. A systematic laboratory study of the permeability of the agricultural films to nine fumigants was conducted to evaluate the performance of commonly used film products, including polyethylene, metalized, and high-barrier films. The permeability, as expressed by mass transfer coefficient (cm/h), of 27 different films from 13 manufacturers ranged from below 1 × 10(-4) cm/h to above 10 cm/h at 25 °C under ambient relative humidity test conditions. The wide range in permeability of commercially available films demonstrates the need to use films which are appropriate for the fumigation application. The effects of environmental factors, such as temperature and humidity, on the film permeability were also investigated. It was found that high relative humidity could drastically increase the permeability of the high-barrier films. The permeability of some high-barrier films was increased by 2-3 orders of magnitude when the films were tested at high relative humidity. Increasing the temperature from 25 to 40 °C increased the permeability for some high-barrier films up to 10 times more than the permeability at 25 °C, although the effect was minimal for several of these films. Analysis of the distribution of the permeability of the films under ambient humidity conditions to nine fumigants indicated that the 27 films largely followed the material type, although the permeability varied considerably among the films of similar material.

Intestinal permeability study of minoxidil: assessment of minoxidil as a high permeability reference drug for biopharmaceutics classification.

PubMed

Ozawa, Makoto; Tsume, Yasuhiro; Zur, Moran; Dahan, Arik; Amidon, Gordon L

2015-01-05

The purpose of this study was to evaluate minoxidil as a high permeability reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil was determined in in situ intestinal perfusion studies in rodents and permeability studies across Caco-2 cell monolayers. The permeability of minoxidil was compared with that of metoprolol, an FDA reference drug for BCS classification. In rat perfusion studies, the permeability of minoxidil was somewhat higher than that of metoprolol in the jejunum, while minoxidil showed lower permeability than metoprolol in the ileum. The permeability of minoxidil was independent of intestinal segment, while the permeability of metoprolol was region-dependent. Similarly, in mouse perfusion study, the jejunal permeability of minoxidil was 2.5-fold higher than that of metoprolol. Minoxidil and metoprolol showed similar permeability in Caco-2 study at apical pH of 6.5 and basolateral pH of 7.4. The permeability of minoxidil was independent of pH, while metoprolol showed pH-dependent transport in Caco-2 study. Minoxidil exhibited similar permeability in the absorptive direction (AP-BL) in comparison with secretory direction (BL-AP), while metoprolol had higher efflux ratio (ER > 2) at apical pH of 6.5 and basolateral pH of 7.4. No concentration-dependent transport was observed for either minoxidil or metoprolol transport in Caco-2 study. Verapamil did not alter the transport of either compounds across Caco-2 cell monolayers. The permeability of minoxidil was independent of both pH and intestinal segment in intestinal perfusion studies and Caco-2 studies. Caco-2 studies also showed no involvement of carrier mediated transport in the absorption process of minoxidil. These results suggest that minoxidil may be an acceptable reference drug for BCS high permeability classification. However, minoxidil exhibited higher jejunal permeability than metoprolol and thus to use minoxidil as a reference drug would raise the permeability criteria for BCS high permeability classification.

Water and solute permeability of rat lung caveolae: high permeabilities explained by acyl chain unsaturation.

PubMed

Hill, Warren G; Almasri, Eyad; Ruiz, W Giovanni; Apodaca, Gerard; Zeidel, Mark L

2005-07-01

Caveolae are invaginated membrane structures with high levels of cholesterol, sphingomyelin, and caveolin protein that are predicted to exist as liquid-ordered domains with low water permeability. We isolated a caveolae-enriched membrane fraction without detergents from rat lung and characterized its permeability properties to nonelectrolytes and protons. Membrane permeability to water was 2.85 +/- 0.41 x 10(-3) cm/s, a value 5-10 times higher than expected based on comparisons with other cholesterol and sphingolipid-enriched membranes. Permeabilities to urea, ammonia, and protons were measured and found to be moderately high for urea and ammonia at 8.85 +/- 2.40 x 10(-7)and 6.84 +/- 1.03 x 10(-2) respectively and high for protons at 8.84 +/- 3.06 x 10(-2) cm/s. To examine whether caveolin or other integral membrane proteins were responsible for high permeabilities, liposomes designed to mimic the lipids of the inner and outer leaflets of the caveolar membrane were made. Osmotic water permeability to both liposome compositions were determined and a combined inner/outer leaflet water permeability was calculated and found to be close to that of native caveolae at 1.58 +/- 1.1 x 10(-3) cm/s. In caveolae, activation energy for water flux was high (19.4 kcal/mol) and water permeability was not inhibited by HgCl2; however, aquaporin 1 was detectable by immunoblotting. Immunostaining of rat lung with AQP1 and caveolin antisera revealed very low levels of colocalization. We conclude that aquaporin water channels do not contribute significantly to the observed water flux and that caveolae have relatively high water and solute permeabilities due to the high degree of unsaturation in their fatty acyl chains.

Microglia cyclooxygenase-2 activity in experimental gliomas: possible role in cerebral edema formation.

PubMed

Badie, Behnam; Schartner, Jill M; Hagar, Aaron R; Prabakaran, Sakthivel; Peebles, Todd R; Bartley, Becky; Lapsiwala, Samir; Resnick, Daniel K; Vorpahl, Jessica

2003-02-01

Cerebral edema is responsible for significant morbidity and mortality in patients harboring malignant gliomas. To examine the role of inflammatory cells in brain edema formation, we studied the expression cyclooxygenase (COX)-2, a key enzyme in arachidonic acid metabolism, by microglia in the C6 rodent glioma model. The expression of COX-2 in primary microglia cultures obtained from intracranial rat C6 gliomas was examined using reverse transcription-PCR, Western analysis, and prostaglandin E(2) (PGE(2)) enzyme immunoassay. Blood-tumor barrier permeability was studied in the same tumor model using magnetic resonance imaging. In contrast to C6 glioma cells, microglia isolated from intracranial C6 tumors produced high levels of PGE(2) through a COX-2-dependent pathway. To test whether the observed microglia COX-2 activity played a role in brain edema formation in gliomas, tumor-bearing rats were treated with rofecoxib, a selective COX-2 inhibitor. Rofecoxib was as effective as dexamethasone in decreasing the diffusion of contrast material into the brain parenchyma (P = 0.01, rofecoxib versus control animals), suggesting a reduction in blood-tumor barrier permeability. These findings suggest that glioma-infiltrating microglia are a major source of PGE(2) production through the COX-2 pathway and support the use of COX-2 inhibitors as possible alternatives to glucocorticoids in the treatment of peritumoral edema in patients with malignant brain tumors.

Secondary migration and leakage of methane from a major tight-gas system

NASA Astrophysics Data System (ADS)

Wood, James M.; Sanei, Hamed

2016-11-01

Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere.

Secondary migration and leakage of methane from a major tight-gas system

PubMed Central

Wood, James M.; Sanei, Hamed

2016-01-01

Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere. PMID:27874012

Eotaxin increases monolayer permeability of human coronary artery endothelial cells.

PubMed

Jamaluddin, Md Saha; Wang, Xinwen; Wang, Hao; Rafael, Cubas; Yao, Qizhi; Chen, Changyi

2009-12-01

The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs). Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas Red-labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin, and claudin-1 in a concentration-dependent manner as determined by real-time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580, and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased the phosphorylation of Stat3 and nuclear translocation of NF-kappaB in HCAECs. Eotaxin increases vascular permeability through CCR3, the downregulation of tight junction proteins, increase of oxidative stress, and activation of MAPK p38, Stat3, and NF-kB pathways in HCAECs.

Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.

PubMed Central

Levine, S D; Levine, R D; Worthington, R E; Hays, R M

1976-01-01

Vasopressin increases the permeability of the total urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin. In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in to toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyflurane-treated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well. We conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea. PMID:184113

Inclusion-based effective medium models for the field-scale permeability of 3D fractured rock masses

NASA Astrophysics Data System (ADS)

Ebigbo, Anozie; Lang, Philipp S.; Paluszny, Adriana; Zimmerman, Robert W.

2016-04-01

Fractures that are more permeable than their host rock can act as preferential, or at least additional, pathways for fluid to flow through the rock. The additional transmissivity contributed by these fractures will be of great relevance in several areas of earth science and engineering, such as radioactive waste disposal in crystalline rock, exploitation of fractured hydrocarbon and geothermal reservoirs, or hydraulic fracturing. In describing or predicting flow through fractured rock, the effective permeability of the rock mass, comprising both the rock matrix and a network of fractures, is a crucial parameter, and will depend on several geometric properties of the fractures/networks, such as lateral extent, aperture, orientation, and fracture density. This study investigates the ability of classical inclusion-based effective medium models (following the work of Sævik et al., Transp. Porous Media, 2013) to predict this permeability. In these models, the fractures are represented as thin, spheroidal inclusions, the interiors of which are treated as porous media having a high (but finite) permeability. The predictions of various effective medium models, such as the symmetric and asymmetric self-consistent schemes, the differential scheme, and Maxwell's method, are tested against the results of explicit numerical simulations of mono- and polydisperse isotropic fracture networks embedded in a permeable rock matrix. Comparisons are also made with the Hashin-Shrikman bounds, Snow's model, and Mourzenko's heuristic model (Mourzenko et al., Phys. Rev. E, 2011). This problem is characterised mathematically by two small parameters, the aspect ratio of the spheroidal fractures, α, and the ratio between matrix and fracture permeability, κ. Two different regimes can be identified, corresponding to α/κ < 1 and α/κ > 1. The lower the value of α/κ, the more significant is flow through the matrix. Due to differing flow patterns, the dependence of effective permeability on fracture density differs in the two regimes. When α/κ > 1, a distinct percolation threshold is observed, whereas for α/κ < 1, the matrix is sufficiently transmissive that a percolation-like transition is not observed. The self-consistent effective medium methods show good accuracy for both mono- and polydisperse isotropic fracture networks. Mourzenko's equation is also found to be very accurate, particularly for monodisperse networks. Finally, it is shown that Snow's model essentially coincides with the Hashin-Shtrikman upper bound.

Using FLIM in the study of permeability barrier function of aged and young skin

NASA Astrophysics Data System (ADS)

Xu, P.; Choi, E. H.; Man, M. Q.; Crumrine, D.; Mauro, T.; Elias, P.

2006-02-01

Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that can be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. It has been previously described a permeability barrier defect in humans of advanced age (> 75 years), which in a murine analog >18 mos, could be attributed to reduced lipid synthesis synthesis. However, the functional abnormality in moderately aged mice is due not to decreased lipid synthesis, but rather to a specific defect in stratum corneum (SC) acidification causing impaired lipid processing processing. Endogenous Na +/H + antiporter (NHE1) level was found declined in moderately aged mouse epidermis. This acidification defect leads to perturbed permeability barrier homeostasis through more than one pathways, we addressed suboptimal activation of the essential, lipid-processing enzyme, β-glucocerebrosidase (BGC) is linked to elevated SC pH. Finally, the importance of the epidermis acidity is shown by the normalization of barrier function after exogenous acidification of moderately aged skin.

Unified model for the corneal permeability of related and diverse compounds with respect to their physicochemical properties.

PubMed

Yoshida, F; Topliss, J G

1996-08-01

Corneal permeability data taken from the literature were analyzed for possible quantitative relationships with physicochemical properties. Although a parabolic relationship was obtained with good correlation between lipophilicity, as expressed by the 1-octanol-water partition coefficients, log Poctanol (or the distribution coefficients, log D for ionizable compounds), and the permeability in individual analyses of compound classes such as beta-adrenoceptor blockers and steroids, the correlation was reduced when taken together. However, delta log P (i.e., log Poctanol-log Palkane) correlated inversely with the combined permeability data for beta-blockers and steroids and played a key role as a unifying variable. To a lesser extent, lipophilicity itself also contributes positively to corneal permeation. Even with the addition of miscellaneous compounds such as methanol and ibuprofen, the delta log P and lipophilicity terms were still significant. However, small molecules were likely to be underestimated, which is consistent with penetration via another pathway besides that governed by delta log P and lipophilicity.

Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase

PubMed Central

Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang

2014-01-01

γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes. PMID:24799560

Multi-phase imaging of intermittency at steady state using differential imaging method by X-ray micro-tomography

NASA Astrophysics Data System (ADS)

Gao, Y.; Lin, Q.; Bijeljic, B.; Blunt, M. J.

2017-12-01

To observe intermittency in consolidated rock, we image a steady state flow of brine and decane in Bentheimer sandstone. We devise an experimental method based on X-ray differential imaging method to examine how changes in flow rate impact the pore-scale distribution of fluids during co-injection flow under dynamic flow conditions at steady state. This helps us elucidate the diverse flow regimes (connected, intermittent break-up, or continual break-up of the non-wetting phase pathways) for two capillary numbers. Also, relative permeability curves under both capillary and viscous limited conditions could be measured. We have performed imbibition sample floods using oil-brine and measured steady state relative permeability on a sandstone rock core in order to fully characterize the flow behaviour at low and high Ca. Two sets of experiments at high and low flow rates are provided to explore the time-evolution of the non-wetting phase clusters distribution under different flow conditions. The high flow rate is 0.5 mL/min, whose corresponding capillary number is 7.7×10-6. The low flow rate is 0.02 mL/min, whose capillary number is 3.1×10-7. A procedure based on using high-salinity brine as the contrast phase and applying differential imaging between the dry scan and that of the sample saturation with a 30 wt% Potassium iodide (KI) doped brine help to make sure there is no non-wetting phase in micro-pores. Then the intermittent phase in multiphase flow image at high Ca can be quantified by obtaining the differential image between the 30 wt% KI brine image and the scans that taken at each fixed fractional flow. By using the grey scale histogram distribution of the raw images at each condition, the oil proportion in the intermittent phase can be calculated. The pressure drops at each fractional flow at low and high Ca can be measured by high-precision pressure differential sensors and utilized to calculate to the relative permeability at pore scale. The relative permeability data and fw-Sw relationship obtained by our experiment at pore scale are compared with the data collected from experiments which were conducted at core scale, and they match well.

Numerical simulation of the environmental impact of hydraulic fracturing of tight/shale gas reservoirs on near-surface groundwater: Background, base cases, shallow reservoirs, short-term gas, and water transport

DOE PAGES

Reagan, Matthew T.; Moridis, George J.; Keen, Noel D.; ...

2015-04-18

Hydrocarbon production from unconventional resources and the use of reservoir stimulation techniques, such as hydraulic fracturing, has grown explosively over the last decade. However, concerns have arisen that reservoir stimulation creates significant environmental threats through the creation of permeable pathways connecting the stimulated reservoir with shallower freshwater aquifers, thus resulting in the contamination of potable groundwater by escaping hydrocarbons or other reservoir fluids. This study investigates, by numerical simulation, gas and water transport between a shallow tight-gas reservoir and a shallower overlying freshwater aquifer following hydraulic fracturing operations, if such a connecting pathway has been created. We focus on twomore » general failure scenarios: (1) communication between the reservoir and aquifer via a connecting fracture or fault and (2) communication via a deteriorated, preexisting nearby well. We conclude that the key factors driving short-term transport of gas include high permeability for the connecting pathway and the overall volume of the connecting feature. Production from the reservoir is likely to mitigate release through reduction of available free gas and lowering of reservoir pressure, and not producing may increase the potential for release. We also find that hydrostatic tight-gas reservoirs are unlikely to act as a continuing source of migrating gas, as gas contained within the newly formed hydraulic fracture is the primary source for potential contamination. Such incidents of gas escape are likely to be limited in duration and scope for hydrostatic reservoirs. Reliable field and laboratory data must be acquired to constrain the factors and determine the likelihood of these outcomes.« less

Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo.

PubMed

Sommansson, Anna; Saudi, Wan Salman Wan; Nylander, Olof; Sjöblom, Markus

2013-07-01

Increased intestinal permeability is often associated with epithelial inflammation, leaky gut, or other pathological conditions in the gastrointestinal tract. We recently found that melatonin decreases basal duodenal mucosal permeability, suggesting a mucosal protective mode of action of this agent. The aim of the present study was to elucidate the effects of melatonin on ethanol-, wine-, and HCl-induced changes of duodenal mucosal paracellular permeability and motility. Rats were anesthetized with thiobarbiturate and a ~30-mm segment of the proximal duodenum was perfused in situ. Effects on duodenal mucosal paracellular permeability, assessed by measuring the blood-to-lumen clearance of ⁵¹Cr-EDTA, motility, and morphology, were investigated. Perfusing the duodenal segment with ethanol (10 or 15% alcohol by volume), red wine, or HCl (25-100 mM) induced concentration-dependent increases in paracellular permeability. Luminal ethanol and wine increased, whereas HCl transiently decreased duodenal motility. Administration of melatonin significantly reduced ethanol- and wine-induced increases in permeability by a mechanism abolished by the nicotinic receptor antagonists hexamethonium (iv) or mecamylamine (luminally). Signs of mucosal injury (edema and beginning of desquamation of the epithelium) in response to ethanol exposure were seen only in a few villi, an effect that was histologically not changed by melatonin. Melatonin did not affect HCl-induced increases in mucosal permeability or decreases in motility. Our results show that melatonin reduces ethanol- and wine-induced increases in duodenal paracellular permeability partly via an enteric inhibitory nicotinic-receptor dependent neural pathway. In addition, melatonin inhibits ethanol-induced increases in duodenal motor activity. These results suggest that melatonin may serve important gastrointestinal barrier functions.

A new simplified method for measuring the permeability characteristics of highly porous media

NASA Astrophysics Data System (ADS)

Qin, Yinghong; Zhang, Mingyi; Mei, Guoxiong

2018-07-01

Fluid flow through highly porous media is important in a variety of science and technology fields, including hydrology, chemical engineering, convections in porous media, and others. While many methods have been available to measure the permeability of tight solid materials, such as concrete and rock, the technique for measuring the permeability of highly porous media is limited (such as gravel, aggregated soils, and crushed rock). This study proposes a new simplified method for measuring the permeability of highly porous media with a permeability of 10-8-10-4 m2, using a Venturi tube to gauge the gas flowing rate through the sample. Using crushed rocks and glass beads as the test media, we measure the permeability and inertial resistance factor of six types of single-size aggregate columns. We compare the testing results with the published permeability and inertial resistance factor of crushed rock and of glass beads. We found that in a log-log graph, the permeability and inertial resistance factor of a single-size aggregate heap increases linearly with the mean diameter of the aggregate. We speculate that the proposed simplified method is suitable to efficiently test the permeability and inertial resistance factor of a variety of porous media with an intrinsic permeability of 10-8-10-4 m2.

The role of apoptosis in LDL transport through cultured endothelial cell monolayers.

PubMed

Cancel, Limary M; Tarbell, John M

2010-02-01

We have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for low density lipoprotein (LDL) transport under convective conditions, accounting for more than 90% of the transport [Cancel LM, Fitting A, Tarbell JM. In vitro study of LDL transport under pressurized (convective) conditions. Am J Physiol Heart Circ Physiol 2007;293:H126-32]. To explore the role of apoptosis in the leaky junction pathway, TNFalpha and cycloheximide (TNFalpha/CHX) were used to induce an elevated rate of apoptosis in cultured bovine aortic endothelial cell (BAEC) monolayers and the convective fluxes of LDL and water were measured. Treatment with TNFalpha/CHX induced a 18.3-fold increase in apoptosis and a 4.4-fold increase in LDL permeability. Increases in apoptosis and permeability were attenuated by treatment with the caspase inhibitor Z-VAD-FMK. Water flux increased by 2.7-fold after treatment with TNFalpha/CHX, and this increase was not attenuated by treatment with Z-VAD-FMK. Immunostaining of the tight junction protein ZO-1 showed that TNFalpha/CHX treatment disrupts the tight junction in addition to inducing apoptosis. This disruption is present even when Z-VAD-FMK is used to inhibit apoptosis, and likely accounts for the increase in water flux. We found a strong correlation between the rate of apoptosis and the permeability of BAEC monolayers to LDL. These results demonstrate the potential of manipulating endothelial monolayer permeability by altering the rate of apoptosis pharmacollogicaly. This has implications for the treatment of atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Tonic regulation of vascular permeability

PubMed Central

Curry, Fitz-Roy E.; Adamson, Roger H.

2014-01-01

Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signaling pathways regulated by S1P and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signaling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first reestablishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1 dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up-regulation of RhoA dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium. PMID:23374222

Arsenite induces endothelial cell permeability increase through a reactive oxygen species-vascular endothelial growth factor pathway.

PubMed

Bao, Lingzhi; Shi, Honglian

2010-11-15

As a potent environmental oxidative stressor, arsenic exposure has been reported to exacerbate cardiovascular diseases and increase vascular endothelial cell monolayer permeability. However, the underlying mechanism of this effect is not well understood. In this paper, we test our hypothesis that reactive oxygen species (ROS)-induced vascular endothelial growth factor (VEGF) expression may play an important role in an arsenic-caused increase of endothelial cell monolayer permeability. The mouse brain vascular endothelial cell bEnd3 monolayer was exposed to arsenite for 1, 3, and 6 days. The monolayer permeability, VEGF protein release, and ROS generation were determined. In addition, VE-cadherin and zonula occludens-1 (ZO-1), two membrane structure proteins, were immunostained to elucidate the effects of arsenite on the cell-cell junction. The roles of ROS and VEGF in arsenite-induced permeability was determined by inhibiting ROS with antioxidants and immuno-depleting VEGF with a VEGF antibody. We observed that arsenite increased bEnd3 monolayer permeability, elevated the production of cellular ROS, and increased VEGF release. VE-cadherin and ZO-1 disruptions were also found in cells treated with arsenite. Furthermore, both antioxidant (N-acetyl cysteine and tempol) and the VEGF antibody treatments significantly lowered the arsenite-induced permeability of the bEnd3 monolayer as well as VEGF expression. VE-cadherin and ZO-1 disruptions were also diminished by N-acetyl cysteine and the VEGF antibody. Our data suggest that the increase in VEGF expression caused by ROS may play an important role in the arsenite-induced increase in endothelial cell permeability.

Effect of oxide films on hydrogen permeability of candidate Stirling heater head tube alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuon, S R; Misencik, J A

1981-01-01

High pressure hydrogen has been selected as the working fluid for the developmental automotive Stirling engine. Containment of the working fluid during operation of the engine at high temperatures and at high hydrogen gas pressures is essential for the acceptance of the Stirling engine as an alternative to the internal combustion engine. Most commercial alloys are extremely permeable to pure hydrogen at high temperatures. A program was undertaken at NASA Lewis Research Center (LeRC) to reduce hydrogen permeability in the Stirling engine heater head tubes by doping the hydrogen working fluid with CO or CO/sub 2/. Small additions of thesemore » gases were shown to form an oxide on the inside tube wall and thus reduce hydrogen permeability. A study of the effects of dopant concentration, alloy composition, and effects of surface oxides on hydrogen permeability in candidate heater head tube alloys is summarized. Results showed that hydrogen permeability was similar for iron-base alloys (N-155, A286, IN800, 19-9DL, and Nitronic 40), cobalt-base alloys (HS-188) and nickel-base alloys (IN718). In general, the permeability of the alloys decreased with increasing concentration of CO or CO/sub 2/ dopant, with increasing oxide thickness, and decreasing oxide porosity. At high levels of dopants, highly permeable liquid oxides formed on those alloys with greater than 50% Fe content. Furthermore, highly reactive minor alloying elements (Ti, Al, Nb, and La) had a strong influence on reducing hydrogen permeability.« less

Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

PubMed Central

Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

2015-01-01

The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

The Transcription Factor WIN1/SHN1 Regulates Cutin Biosynthesis in Arabidopsis thaliana[W

PubMed Central

Kannangara, Rubini; Branigan, Caroline; Liu, Yan; Penfield, Teresa; Rao, Vijaya; Mouille, Grégory; Höfte, Herman; Pauly, Markus; Riechmann, José Luis; Broun, Pierre

2007-01-01

The composition and permeability of the cuticle has a large influence on its ability to protect the plant against various forms of biotic and abiotic stress. WAX INDUCER1 (WIN1) and related transcription factors have recently been shown to trigger wax production, enhance drought tolerance, and modulate cuticular permeability when overexpressed in Arabidopsis thaliana. We found that WIN1 influences the composition of cutin, a polyester that forms the backbone of the cuticle. WIN1 overexpression induces compositional changes and an overall increase in cutin production in vegetative and reproductive organs, while its downregulation has the opposite effect. Changes in cutin composition are preceded by the rapid and coordinated induction of several genes known or likely to be involved in cutin biosynthesis. This transcriptional response is followed after a delay by the induction of genes associated with wax biosynthesis, suggesting that the regulation of cutin and wax production by WIN1 is a two-step process. We demonstrate that at least one of the cutin pathway genes, which encodes long-chain acyl-CoA synthetase LACS2, is likely to be directly targeted by WIN1. Overall, our results suggest that WIN1 modulates cuticle permeability in Arabidopsis by regulating genes encoding cutin pathway enzymes. PMID:17449808

The transcription factor WIN1/SHN1 regulates Cutin biosynthesis in Arabidopsis thaliana.

PubMed

Kannangara, Rubini; Branigan, Caroline; Liu, Yan; Penfield, Teresa; Rao, Vijaya; Mouille, Grégory; Höfte, Herman; Pauly, Markus; Riechmann, José Luis; Broun, Pierre

2007-04-01

The composition and permeability of the cuticle has a large influence on its ability to protect the plant against various forms of biotic and abiotic stress. WAX INDUCER1 (WIN1) and related transcription factors have recently been shown to trigger wax production, enhance drought tolerance, and modulate cuticular permeability when overexpressed in Arabidopsis thaliana. We found that WIN1 influences the composition of cutin, a polyester that forms the backbone of the cuticle. WIN1 overexpression induces compositional changes and an overall increase in cutin production in vegetative and reproductive organs, while its downregulation has the opposite effect. Changes in cutin composition are preceded by the rapid and coordinated induction of several genes known or likely to be involved in cutin biosynthesis. This transcriptional response is followed after a delay by the induction of genes associated with wax biosynthesis, suggesting that the regulation of cutin and wax production by WIN1 is a two-step process. We demonstrate that at least one of the cutin pathway genes, which encodes long-chain acyl-CoA synthetase LACS2, is likely to be directly targeted by WIN1. Overall, our results suggest that WIN1 modulates cuticle permeability in Arabidopsis by regulating genes encoding cutin pathway enzymes.

Vinpocetine regulates cation channel permeability of inner retinal neurons in the ischaemic retina.

PubMed

Nivison-Smith, Lisa; Acosta, Monica L; Misra, Stuti; O'Brien, Brendan J; Kalloniatis, Michael

2014-01-01

Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetine's regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regulation of Transient Receptor Potential channels by the phospholipase C pathway

PubMed Central

Rohacs, Tibor

2013-01-01

Transient Receptor Potential (TRP) channels were discovered while analyzing visual mutants in drosophila. The protein encoded by the transient receptor potential (trp) gene is a Ca2+ permeable cation channel activated downstream of the phospholipase C (PLC) pathway. While searching for homologues in other organisms, a surprisingly large number of mammalian TRP channels were cloned. The regulation of TRP channels is quite diverse, but many of them are either activated downstream of the PLC pathway, or modulated by it. This review will summarize the current knowledge on regulation of TRP channels by the PLC pathway, with special focus on TRPC-s, which can be considered as effectors of the PLC pathway, and the heat and capsaicin sensitive TRPV1, which is modulated by the PLC pathway in a complex manner. PMID:23916247

A PKA survival pathway inhibited by DPT-PKI, a new specific cell permeable PKA inhibitor, is induced by T. annulata in parasitized B-lymphocytes.

PubMed

Guergnon, Julien; Dessauge, Frederic; Traincard, François; Cayla, Xavier; Rebollo, Angelita; Bost, Pierre Etienne; Langsley, Gordon; Garcia, Alphonse

2006-08-01

T. annulata, an intracellular pathogenic parasite of the Aplicomplexa protozoan family infects bovine B-lymphocytes and macrophages. Parasitized cells that become transformed survive and proliferate independently of exogenous growth factors. In the present study, we used the isogenic non parasitized BL3 and parasitized TBL3 B cell lines, as a model to evaluate the contribution of two-major PI3-K- and PKA-dependent anti-apoptotic pathways in the survival of T. annulata parasitized B lymphocytes. We found that T. annulata increases PKA activity, induces over-expression of the catalytic subunit and down-regulates the pro-survival phosphorylation state of Akt/PKB. Consistent with a role of PKA activation in survival, two pharmacological inhibitors H89 and KT5720 ablate PKA-dependent survival of parasitized cells. To specifically inhibit PKA pro-survival pathways we linked the DPTsh1 peptide shuttle sequence to PKI(5-24) and we generated DPT-PKI, a cell permeable PKI. DPT-PKI specifically inhibited PKA activity in bovine cell extracts and, as expected, also inhibited the PKA-dependent survival of T. annulata parasitized TBL3 cells. Thus, parasite-dependent constitutive activation of PKA in TBL3 cells generates an anti-apoptotic pathway that can protect T. annulata-infected B cells from apoptosis. These results also indicate that DPT-PKI could be a powerful tool to inhibit PKA pathways in other cell types.

Claudin-2-mediated cation and water transport share a common pore

PubMed Central

Rosenthal, Rita; Günzel, Dorothee; Krug, Susanne M.; Schulzke, Jörg-Dieter; Fromm, Michael; Yu, Alan S.L.

2016-01-01

Aim Claudin-2 is a tight junction protein typically located in “leaky” epithelia exhibiting large paracellular permeabilities like small intestine and proximal kidney tubule. Former studies revealed that claudin-2 forms paracellular channels for small cations like sodium and potassium and also paracellular channels for water. This study analyzes whether the diffusive transport of sodium and water occurs through a common pore of the claudin-2 channel. Methods Wild-type claudin-2 and different claudin-2 mutants were expressed in MDCK I kidney tubule cells using an inducible system. Ion and water permeability and the effect of blocking reagents on both were investigated on different clones of the mutants. Results Neutralization of a negatively charged cation interaction site in the pore with the mutation, D65N, decreased both, sodium permeability and water permeability. Claudin-2 mutants (I66C and S68C) with substitution of the pore-lining amino acids with cysteine were used to test the effect of steric blocking of the claudin-2 pore by thiol-reactive reagents. Addition of thiol-reactive reagents to these mutants simultaneously decreased conductance and water permeability. Remarkably, all experimental perturbations caused parallel changes in ion conductance and water permeability, disproving different or independent passage pathways. Conclusion Our results indicate that claudin-2-mediated cation and water transport are frictionally coupled and share a common pore. This pore is lined and determined in permeability by amino acid residues of the first extracellular loop of claudin-2. PMID:27359349

Structural and Kinetic Characterization of the LPS Biosynthetic Enzyme D-alpha,beta-D-heptose-1,7-bisphosphate Phosphatase (GmhB) from Escherichia coli

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, P.; Sugiman-Marangos, S; Zhang, K

2010-01-01

Lipopolysaccharide is a major component of the outer membrane of Gram-negative bacteria and provides a permeability barrier to many commonly used antibiotics. ADP-heptose residues are an integral part of the LPS inner core, and mutants deficient in heptose biosynthesis demonstrate increased membrane permeability. The heptose biosynthesis pathway involves phosphorylation and dephosphorylation steps not found in other pathways for the synthesis of nucleotide sugar precursors. Consequently, the heptose biosynthetic pathway has been marked as a novel target for antibiotic adjuvants, which are compounds that facilitate and potentiate antibiotic activity. D-{alpha},{beta}-D-Heptose-1,7-bisphosphate phosphatase (GmhB) catalyzes the third essential step of LPS heptose biosynthesis.more » This study describes the first crystal structure of GmhB and enzymatic analysis of the protein. Structure-guided mutations followed by steady state kinetic analysis, together with established precedent for HAD phosphatases, suggest that GmhB functions through a phosphoaspartate intermediate. This study provides insight into the structure-function relationship of GmhB, a new target for combatting Gram-negative bacterial infection.« less

Application of carbonate cyclostratigraphy and borehole geophysics to delineate porosity and preferential flow in the karst limestone of the Biscayne aquifer, SE Florida

USGS Publications Warehouse

Cunningham, K.J.; Renken, R.A.; Wacker, M.A.; Zygnerski, M.R.; Robinson, E.; Shapiro, A.M.; Wingard, G.L.

2006-01-01

Combined analyses of cores, borehole geophysical logs, and cyclostratigraphy produced a new conceptual hydrogeologic framework for the triple-porosity (matrix, touching-vug, and conduit porosity) karst limestone of the Biscayne aquifer in a 0.65 km2 study area, SE Florida. Vertical lithofacies successions, which have recurrent stacking patterns, fit within high-frequency cycles. We define three ideal high-frequency cycles as: (1) upward-shallowing subtidal cycles, (2) upward-shallowing paralic cycles, and (3) aggradational subtidal cycles. Digital optical borehole images, tracers, and flow meters indicate that there is a predictable vertical pattern of porosity and permeability within the three ideal cycles, because the distribution of porosity and permeability is related to lithofacies. Stratiform zones of high permeability commonly occur just above flooding surfaces in the lower part of upward-shallowing subtidal and paralic cycles, forming preferential groundwater flow zones. Aggradational subtidal cycles are either mostly high-permeability zones or leaky, low-permeability units. In the study area, groundwater flow within stratiform high-permeability zones is through a secondary pore system of touching-vug porosity principally related to molds of burrows and pelecypods and to interburrow vugs. Movement of a dye-tracer pulse observed using a borehole fluid-temperature tool during a conservative tracer test indicates heterogeneous permeability. Advective movement of the tracer appears to be most concentrated within a thin stratiform flow zone contained within the lower part of a high-frequency cycle, indicating a distinctly high relative permeability for this zone. Borehole flow-meter measurements corroborate the relatively high permeability of the flow zone. Identification and mapping of such high-permeability flow zones is crucial to conceptualization of karst groundwater flow within a cyclostratigraphic framework. Many karst aquifers are included in cyclic platform carbonates. Clearly, a cyclostratigraphic approach that translates carbonate aquifer heterogeneity into a consistent framework of correlative units will improve simulation of karst groundwater flow. ?? 2006 Geological Society of America.

A Cell-Permeable Inhibitor to Trap Gαq Proteins in the Empty Pocket Conformation

PubMed Central

Schmitz, Anna-Lena; Schrage, Ramona; Gaffal, Evelyn; Charpentier, Thomas H.; Wiest, Johannes; Hiltensperger, Georg; Morschel, Julia; Hennen, Stephanie; Häußler, Daniela; Horn, Velten; Wenzel, Daniela; Grundmann, Manuel; Büllesbach, Katrin M.; Schröder, Ralf; Brewitz, H. Henning; Schmidt, Johannes; Gomeza, Jesús; Galés, Céline; Fleischmann, Bernd K.; Tüting, Thomas; Imhof, Diana; Tietze, Daniel; Gütschow, Michael; Holzgrabe, Ulrike; Sondek, John; Harden, T. Kendall; Mohr, Klaus; Kostenis, Evi

2015-01-01

SUMMARY In spite of the crucial role of heterotrimeric G proteins as molecular switches transmitting signals from G protein-coupled receptors, their selective manipulation with small molecule, cell-permeable inhibitors still remains an unmet challenge. Here, we report that the small molecule BIM-46187, previously classified as pan-G protein inhibitor, preferentially silences Gαq signaling in a cellular context-dependent manner. Investigations into its mode of action reveal that BIM traps Gαq in the empty pocket conformation by permitting GDP exit but interdicting GTP entry, a molecular mechanism not yet assigned to any other small molecule Gα inhibitor to date. Our data show that Gα proteins may be “frozen” pharmacologically in an intermediate conformation along their activation pathway and propose a pharmacological strategy to specifically silence Gα subclasses with cell-permeable inhibitors. PMID:25036778

Elastic and electrical properties and permeability of serpentinites from Atlantis Massif, Mid-Atlantic Ridge

NASA Astrophysics Data System (ADS)

Falcon-Suarez, Ismael; Bayrakci, Gaye; Minshull, Tim A.; North, Laurence J.; Best, Angus I.; Rouméjon, Stéphane

2017-11-01

Serpentinized peridotites co-exist with mafic rocks in a variety of marine environments including subduction zones, continental rifts and mid-ocean ridges. Remote geophysical methods are crucial to distinguish between them and improve the understanding of the tectonic, magmatic and metamorphic history of the oceanic crust. But, serpentinite peridotites exhibit a wide range of physical properties that complicate such a distinction. We analysed the ultrasonic P- and S-wave velocities (Vp, Vs) and their respective attenuation (Qp-1, Qs-1), electrical resistivity and permeability of four serpentinized peridotite samples from the southern wall of the Atlantis Massif, Mid-Atlantic Ridge, collected during International Ocean Discovery Program Expedition 357. The measurements were taken over a range of loading-unloading stress paths (5-45 MPa), using ∼1.7 cm length, 5 cm diameter samples horizontally extracted from the original cores drilled on the seafloor. The measured parameters showed variable degrees of stress dependence, but followed similar trends. Vp, Vs, resistivity and permeability show good inter-correlations, while relationships that included Qp-1 and Qs-1 are less clear. Resistivity showed high contrast between highly serpentinized ultramafic matrix (>50 Ω m) and mechanically/geochemically altered (magmatic/hydrothermal-driven alteration) domains (<20 Ω m). This information together with the elastic constants (Vp/Vs ratio and bulk moduli) of the samples allowed us to infer useful information about the degree of serpentinization and the alteration state of the rock, contrasted by petrographic analysis. This study shows the potential of combining seismic techniques and controlled source electromagnetic surveys for understanding tectonomagmatic processes and fluid pathways in hydrothermal systems.

Eotaxin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells

PubMed Central

Jamaluddin, Md Saha; Wang, Xinwen; Wang, Hao; Rafael, Cubas; Yao, Qizhi; Chen, Changyi

2009-01-01

Objective The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs). Methods and Results Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas-Red-labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin and claudin-1 in a concentration-dependent manner as determined by real time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580 and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased phosphorylation of Stat3 and nuclear translocation of NF-κB in HCAECs. Conclusions Eotaxin increases vascular permeability through CCR3, the down regulation of tight junction proteins, increase of oxidative stress and activation of MAPK p38, Stat3 and NF-kB pathways in HCAECs. PMID:19778943

Novel Strategy for Tracking the Microbial Degradation of Azo Dyes with Different Polarities in Living Cells.

PubMed

Liu, Fei; Xu, Meiying; Chen, Xingjuan; Yang, Yonggang; Wang, Haiji; Sun, Guoping

2015-10-06

Direct visualization evidence is important for understanding the microbial degradation mechanisms. To track the microbial degradation pathways of azo dyes with different polar characterizations, sensors based on the fluorescence resonance energy transfer (FRET) from 1,8-naphthalimide to azo dyes were synthesized, in which the quenched fluorescence will recover when the azo bond was cleaved. In living cells, the sensor-tracking experiment showed that the low polarity and hydrophobic azo dye can be taken up into the cells and reduced inside the cells, whereas the high polarity and hydrophilic azo dye can be reduced only outside the cells because of the selective permeability of the cell membranes. These results indicated that there were two different bacterial degradation pathways available for different polarity azo dyes. To our knowledge, no fluorescent sensor has yet been designed for illuminating the microbial degradation mechanisms of organic pollutants with different characteristics.

Biofilm-induced calcium carbonate precipitation: application in the subsurface

NASA Astrophysics Data System (ADS)

Phillips, A. J.; Eldring, J.; Lauchnor, E.; Hiebert, R.; Gerlach, R.; Mitchell, A. C.; Esposito, R.; Cunningham, A. B.; Spangler, L.

2012-12-01

We have investigated mitigation strategies for sealing high permeability regions, like fractures, in the subsurface. This technology has the potential to, for example, improve the long-term security of geologically-stored carbon dioxide (CO2) by sealing fractures in cap rocks or to mitigate leakage pathways to prevent contamination of overlying aquifers from hydraulic fracturing fluids. Sealing technologies using low-viscosity fluids are advantageous since they potentially reduce the necessary injection pressures and increase the radius of influence around injection wells. In this technology, aqueous solutions and suspensions are used to promote microbially-induced mineral precipitation which can be applied in subsurface environments. To this end, a strategy was developed to twice seal a hydraulically fractured, 74 cm (2.4') diameter Boyles Sandstone core, collected in North-Central Alabama, with biofilm-induced calcium carbonate (CaCO3) precipitates under ambient pressures. Sporosarcina pasteurii biofilms were established and calcium and urea containing reagents were injected to promote saturation conditions favorable for CaCO3 precipitation followed by growth reagents to resuscitate the biofilm's ureolytic activity. Then, in order to evaluate this process at relevant deep subsurface pressures, a novel high pressure test vessel was developed to house the 74 cm diameter core under pressures as high as 96 bar (1,400 psi). After determining that no impact to the fracture permeability occurred due to increasing overburden pressure, the fractured core was sealed under subsurface relevant pressures relating to 457 meters (1,500 feet) below ground surface (44 bar (650 psi) overburden pressure). After fracture sealing under both ambient and subsurface relevant pressure conditions, the sandstone core withstood three times higher well bore pressure than during the initial fracturing event, which occurred prior to biofilm-induced CaCO3 mineralization. These studies suggest biofilm-induced CaCO3 precipitation technologies may potentially seal and strengthen high permeability regions or fractures (either natural or induced) in the subsurface. Novel high pressure test vessel to investigate biogeochemical processes under relevant subsurface scales and pressures.

Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

PubMed

Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

2017-08-01

Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

Predicting mineral precipitation in fractures: The influence of local heterogeneity on the feedback between precipitation and permeability

NASA Astrophysics Data System (ADS)

Jones, T.; Detwiler, R. L.

2016-12-01

Long-term subsurface energy production and contaminant storage strategies often rely on induced-mineralization to control the transport of dissolved ions. In low-permeability rocks, precipitation is most likely to occur in fractures that act as leakage pathways for fluids that are in chemical disequilibrium with the formation minerals. These fractures are commonly idealized as parallel-plate channels with uniform surface mineralogy, and as a result, our predictions often suggest that precipitation leads to fast permeability reduction. However, natural fractures contain both heterogeneous mineralogy and three-dimensional surface roughness, and our understanding of how precipitation affects local permeability in these environments is limited. To examine the impacts of local heterogeneity on the feedback between mineral precipitation and permeability, we performed two long-term experiments in transparent analog fractures: (i) uniform-aperture and (ii) variable-aperture. We controlled the initial heterogeneous surface mineralogy in both experiments by seeding the bottom borosilicate fracture surfaces with randomly distributed clusters of CaCO3 crystals. Continuous flow ISCO pumps injected a well-mixed CaCl2-NaHCO3 solution, log(ΩCaCO3) = 1.44, into the fracture at 0.5 ml/min and transmitted-light techniques provided high-resolution (83 x 83 µm), direct measurements of aperture and fluid transport across the fracture. In experiment (i), precipitation decreased local aperture at discrete CaCO3 reaction sites near the fracture inlet, but transport variations across the fracture remained relatively small due to the initial lack of aperture heterogeneity. In contrast, the feedback between precipitation and aperture in experiment (ii) focused flow into large-aperture, preferential flow paths that contained significantly less CaCO3 area than the fracture scale average. Precipitation-induced aperture reduction in (ii) reduced dissolved ion transport into small-aperture regions of the fracture that were abundant with CaCO3 and led to a 72% decrease in measured precipitation rate. These results suggest that incorporating the effects of local heterogeneity may dramatically improve our ability to predict precipitation-induced permeability alterations in fractured rocks.

Near-surface, marine seismic-reflection data defines potential hydrogeologic confinement bypass in a tertiary carbonate aquifer, southeastern Florida

USGS Publications Warehouse

Cunningham, Kevin J.; Walker, Cameron; Westcott, Richard L.

2012-01-01

Approximately 210 km of near-surface, high-frequency, marine seismic-reflection data were acquired on the southeastern part of the Florida Platform between 2007 and 2011. Many high-resolution, seismic-reflection profiles, interpretable to a depth of about 730 m, were collected on the shallow-marine shelf of southeastern Florida in water as shallow as 1 m. Landward of the present-day shelf-margin slope, these data image middle Eocene to Pleistocene strata and Paleocene to Pleistocene strata on the Miami Terrace. This high-resolution data set provides an opportunity to evaluate geologic structures that cut across confining units of the Paleocene to Oligocene-age carbonate rocks that form the Floridan aquifer system.Seismic profiles image two structural systems, tectonic faults and karst collapse structures, which breach confining beds in the Floridan aquifer system. Both structural systems may serve as pathways for vertical groundwater flow across relatively low-permeability carbonate strata that separate zones of regionally extensive high-permeability rocks in the Floridan aquifer system. The tectonic faults occur as normal and reverse faults, and collapse-related faults have normal throw. The most common fault occurrence delineated on the reflection profiles is associated with karst collapse structures. These high-frequency seismic data are providing high quality structural analogs to unprecedented depths on the southeastern Florida Platform. The analogs can be used for assessment of confinement of other carbonate aquifers and the sealing potential of deeper carbonate rocks associated with reservoirs around the world.

Claudin expression in follicle-associated epithelium of rat Peyer's patches defines a major restriction of the paracellular pathway.

PubMed

Markov, A G; Falchuk, E L; Kruglova, N M; Radloff, J; Amasheh, S

2016-01-01

Members of the tight junction protein family of claudins have been demonstrated to specifically determine paracellular permeability of the intestinal epithelium. In small intestinal mucosa, which is generally considered to be a leaky epithelium, Peyer's patches are a primary part of the immune system. The aim of this study was to analyse the tight junctional barrier of follicle-associated epithelium covering Peyer's patches (lymphoid follicles). Employing small intestinal tissue specimens of male Wistar rats, electrophysiological analyses including the Ussing chamber technique, marker flux measurements and one-path impedance spectroscopy were performed. Morphometry of HE-stained tissue sections was taken into account. Claudin expression and localization was analysed by immunoblotting and confocal laser scanning immunofluorescence microscopy. Almost twofold higher parameters of epithelial and transepithelial tissue resistance and a markedly lower permeability for the paracellular permeability markers 4 and 20 kDa FITC-dextran were detected in follicle-associated epithelium compared to neighbouring villous epithelium. Analysis of claudin expression and localization revealed a stronger expression of major sealing proteins in follicle-associated epithelium, including claudin-1, claudin-4, claudin-5 and claudin-8. Therefore, the specific expression and localization of claudins is in accordance with barrier properties of follicle-associated epithelium vs. neighbouring villous epithelium. We demonstrate that follicle-associated epithelium is specialized to ensure maximum restriction of the epithelial paracellular pathway in Peyer's patches by selective sealing of tight junctions. This results in an exclusive transcellular pathway of epithelial cells as the limiting and mandatory route for a controlled presentation of antigens to the underlying lymphocytes under physiological conditions. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Origin Of Methane Gas And Migration Through The Gas Hydrate Stability Zone Beneath The Permafrost Zone

NASA Astrophysics Data System (ADS)

Uchida, T.; Waseda, A.; Namikawa, T.

2005-12-01

In 1998 and 2002 Mallik wells were drilled at Mackenzie Delta in the Canadian Arctic that clarified the characteristics of gas hydrate-dominant sandy layers at depths from 890 to 1110 m beneath the permafrost zone. Continuous downhole well log data as well as visible gas hydrates have confirmed pore-space hydrate as intergranular pore filling within sandy layers whose saturations are up to 80% in pore volume, but muddy sediments scarcely contain. Plenty of gas hydrate-bearing sand core samples have been obtained from the Mallik wells. According to grain size distributions pore-space hydrate is dominant in medium- to very fine-grained sandy strata. Methane gas accumulation and original pore space large enough to occur within host sediments may be required for forming highly saturated gas hydrate in pore system. The distribution of a porous and coarser-grained host rock should be one of the important factors to control the occurrence of gas hydrate, as well as physicochemical conditions. Subsequent analyses in sedimentology and geochemistry performed on gas hydrate-bearing sandy core samples also revealed important geologic and sedimentological controls on the formation and concentration of natural gas hydrate. This appears to be a similar mode for conventional oil and gas accumulations. It is necessary for investigating subsurface fluid flow behaviors to evaluate both porosity and permeability of gas hydrate-bearing sandy sediments, and the measurements of water permeability for them indicate that highly saturated sands may have permeability of a few millidarcies. The isotopic data of methane show that hydrocarbon gas contained in gas hydrate is generated by thermogenic decomposition of kerogen in deep mature sediments. Based on geochemical and geological data, methane is inferred to migrate upward closely associated with pore water hundreds of meters into and through the hydrate stability zone partly up to the permafrost zone and the surface along faults and permeable sandy pathways. It should be remarked that there are many similar features in appearance and characteristics between the terrestrial and deep marine areas such as Nankai Trough with observations of well-interconnected and highly saturated pore-space hydrate.

Biostratigraphy and structure of paleozoic host rocks and their relationship to Carlin-type gold deposits in the Jerritt Canyon mining district, Nevada

USGS Publications Warehouse

Peters, S.G.; Armstrong, A.K.; Harris, A.G.; Oscarson, R.L.; Noble, P.J.

2003-01-01

The Jerritt Canyon mining district in the northern Independence Range, northern Nevada, contains multiple, nearly horizontal, thrust masses of platform carbonate rocks that are exposed in a series of north- to northeast-elongated, tectonic windows through rocks of the Roberts Mountains allochthon. The Roberts Mountains allochthon was emplaced during the Late Devonian to Early Mississippian Antler orogeny. These thrust masses contain structurally and stratigraphically controlled Carlin-type gold deposits. The gold deposits are hosted in tectonically truncated units of the Silurian to Devonian Hanson Creek and Roberts Mountains Formations that lie within structural slices of an Eastern assemblage of Cambrian to Devonian carbonate rocks. In addition, these multiply thrust-faulted and folded host rocks are structurally interleaved with Mississippian siliciclastic rocks and are overlain structurally by Cambrian to Devonian siliciclastic units of the Roberts Mountains allochthon. All sedimentary rocks were involved in thrusting, high-angle faulting, and folding, and some of these events indicate substantial late Paleozoic and/or Mesozoic regional shortening. Early Pennsylvanian and late Eocene dikes also intrude the sedimentary rocks. These rocks all were uplifted into a northeast-trending range by subsequent late Cenozoic Basin and Range faulting. Eocene sedimentary and volcanic rocks flank part of the range. Pathways of hydrothermal fluid flow and locations of Carlin-type gold orebodies in the Jerritt Canyon mining district were controlled by structural and host-rock geometries within specific lithologies of the stacked thrust masses of Eastern assemblage rocks. The gold deposits are most common proximal to intersections of northeast-striking faults, northwest-striking dikes, and thrust planes that lie adjacent to permeable stratigraphic horizons. The host stratigraphic units include carbonate sequences that contained primary intercrystalline permeability, which provided initial pathways for fluid flow and later served as precipitation sites for ore minerals. Alteration, during, and perhaps prior to mineralization, enhanced primary permeability by dissolution, by removal of calcite, and by formation of dolomite. Ore-stage sulfide minerals and alteration minerals commonly precipitated in pore spaces among dolomite grains. Microveinlets and microbrecciation in zones of intense alteration also provided networks of secondary permeability that further enhanced fluid flux and produced additional sites for ore deposition.

Simulating the heterogeneity in braided channel belt deposits: 2. Examples of results and comparison to natural deposits

NASA Astrophysics Data System (ADS)

Guin, Arijit; Ramanathan, Ramya; Ritzi, Robert W.; Dominic, David F.; Lunt, Ian A.; Scheibe, Timothy D.; Freedman, Vicky L.

2010-04-01

In part 1 of this paper (Ramanathan et al., 2010b) we presented a methodology and a code for modeling the hierarchical sedimentary architecture in braided channel belt deposits. Here in part 2, the code was used to create a digital model of this architecture and the corresponding spatial distribution of permeability. The simulated architecture was compared to the real stratal architecture observed in an abandoned channel belt. The comparisons included assessments of similarity which were both qualitative and quantitative. The qualitative comparisons show that the geometries of unit types within the synthetic deposits are generally consistent with field observations. The unit types in the synthetic deposits would generally be recognized as representing their counterparts in nature, including cross stratasets, lobate and scroll bar deposits, and channel fills. Furthermore, the synthetic deposits have a hierarchical spatial relationship among these units consistent with observations from field exposures and geophysical images. In quantitative comparisons the proportions and the length, width, and height of unit types at different scales, across all levels of the stratal hierarchy, compare well between the synthetic and the natural deposits. A number of important attributes of the synthetic channel belt deposits are shown to be influenced by more than one level within the hierarchy of stratal architecture. First, the high-permeability open-framework gravels connected across all levels and thus formed preferential flow pathways; open-framework gravels are known to form preferential flow pathways in natural channel belt deposits. The nature of a connected cluster changed across different levels of the stratal hierarchy, and as a result of the geologic structure, the connectivity occurs at proportions of open-framework gravels below the theoretical percolation threshold for random infinite media. Second, when the channel belt model was populated with permeability distributions by lowest-level unit type, the composite permeability semivariogram contained structures that were identifiable at more than one scale, and each of these structures could be directly linked to unit types of different scales existing at different levels within the hierarchy of strata. These collective results are encouraging with respect to our goal that this model be relevant for testing ideas in future research on flow and transport in aquifers and reservoirs with multiscale heterogeneity.

Human scalp permeability to the chemical warfare agent VX.

PubMed

Rolland, P; Bolzinger, M-A; Cruz, C; Briançon, S; Josse, D

2011-12-01

The use of chemical warfare agents such as VX in terrorism act might lead to contamination of the civilian population. Human scalp decontamination may require appropriate products and procedures. Due to ethical reasons, skin decontamination studies usually involve in vitro skin models, but human scalp skin samples are uncommon and expensive. The purpose of this study was to characterize the in vitro permeability to VX of human scalp, and to compare it with (a) human abdominal skin, and (b) pig skin from two different anatomic sites: ear and skull roof, in order to design a relevant model. Based on the VX skin permeation kinetics and distribution, we demonstrated that (a) human scalp was significantly more permeable to VX than abdominal skin and (b) pig-ear skin was the most relevant model to predict the in vitro human scalp permeability. Our results indicated that the follicular pathway significantly contributed to the skin absorption of VX through human scalp. In addition, the hair follicles and the stratum corneum significantly contributed to the formation of a skin reservoir for VX. Copyright © 2011 Elsevier Ltd. All rights reserved.

Investigation on the Permeability Evolution of Gypsum Interlayer Under High Temperature and Triaxial Pressure

NASA Astrophysics Data System (ADS)

Tao, Meng; Yechao, You; Jie, Chen; Yaoqing, Hu

2017-08-01

The permeability of the surrounding rock is a critical parameter for the designing and assessment of radioactive waste disposal repositories in the rock salt. Generally, in the locations that are chosen for radioactive waste storage, the bedded rock salt is a sedimentary rock that contains NaCl and Na2SO4. Most likely, there are also layers of gypsum ( {CaSO}_{ 4} \\cdot 2 {H}_{ 2} {O)} present in the salt deposit. Radioactive wastes emit a large amount of heat and hydrogen during the process of disposal, which may result in thermal damage of the surrounding rocks and cause a great change in their permeability and tightness. Therefore, it is necessary to investigate the permeability evolution of the gypsum interlayer under high temperature and high pressure in order to evaluate the tightness and security of the nuclear waste repositories in bedded rock salt. In this study, a self-designed rock triaxial testing system by which high temperature and pressure can be applied is used; the μCT225kVFCB micro-CT system is also employed to investigate the permeability and microstructure of gypsum specimens under a constant hydrostatic pressure of 25 MPa, an increasing temperature (ranging from 20 to 650 °C), and a variable inlet gas pressure (1, 2, 4, 6 MPa). The experimental results show: (a) the maximum permeability measured during the whole experiment is less than 10-17 m2, which indicates that the gypsum interlayer has low permeability under high temperature and pressure that meet the requirements for radioactive waste repository. (b) Under the same temperature, the permeability of the gypsum specimen decreases at the beginning and then increases as the pore pressure elevates. When the inlet gas pressure is between 0 and 2 MPa, the Klinkenberg effect is very pronounced. Then, as the pore pressure increases, the movement behavior of gas molecules gradually changes from free motion to forced directional motion. So the role of free movement of gas molecules gradually reduced, which eventually leads to a decrease in permeability. When the inlet gas pressure is between 2 and 6 MPa, the Klinkenberg effect dribbles away, and the gas flow gradually obeys to the Darcy's law. Hence, the permeability increased with the increase in inlet gas pressure. (c) The curve of permeability versus temperature is divided into five stages based on its gradient. In the temperature range of 20-100 °C, the permeability of gypsum decreased slowly when the temperature decreased. From 100 to 200 °C, the permeability of gypsum increased dramatically when the temperature increased. However, a dramatic increase in permeability was observed from 200 to 450 °C. Subsequently, in the temperature range of 450-550 °C, due to closure of pores and fractures, the permeability of the specimens slowly lessened when the temperature increased. From 550 to 650 °C, the permeability of gypsum slightly increased when the temperature increased; (d) the micro-cracks and porosity obtained from the CT images show a high degree of consistency to the permeability evolution; (e) when compared to the permeability evolutions of sandstone, granite, and lignite, gypsum exhibits a stable evolution trend of permeability and has a much greater threshold temperature when its permeability increases sharply. The results of the paper may provide essential and valuable references for the design and construction of high-level radioactive wastes repository in bedded salt rock containing gypsum interlayers.

Effect of human rhinovirus infection on airway epithelium tight junction protein disassembly and transepithelial permeability.

PubMed

Looi, Kevin; Troy, Niamh M; Garratt, Luke W; Iosifidis, Thomas; Bosco, Anthony; Buckley, Alysia G; Ling, Kak-Ming; Martinovich, Kelly M; Kicic-Starcevich, Elizabeth; Shaw, Nicole C; Sutanto, Erika N; Zosky, Graeme R; Rigby, Paul J; Larcombe, Alexander N; Knight, Darryl A; Kicic, Anthony; Stick, Stephen M

2016-10-11

No studies have assessed the effects of human rhinovirus (HRV) infection on epithelial tight junctions (TJs) and resultant barrier function. To correlate viral infection with TJ disassembly, epithelial barrier integrity, and function. Human airway epithelial cells were infected with HRV minor serotype 1B (HRV-1B) at various 50% tissue culture infectivity doses (TCID 50 ) over 72 hours. HRV replication was assessed by quantitative-polymerase chain reaction (qPCR) while cell viability and apoptosis were assessed by proliferation and apoptotic assays, respectively. Protein expression of claudin-1, occludin, and zonula occludens protein-1 (ZO-1) was assessed using In-Cell™ Western assays. Transepithelial permeability assays were performed to assess effects on barrier functionality. RT 2 Profiler focused qPCR arrays and pathway analysis evaluating associations between human TJ and antiviral response were performed to identify potential interactions and pathways between genes of interests. HRV-1B infection affected viability that was both time and TCID 50 dependent. Significant increases in apoptosis and viral replication post-infection correlated with viral titer. Viral infection significantly decreased claudin-1 protein expression at the lower TCID 50 , while a significant decrease in all three TJ protein expressions occurred at higher TCID 50 . Decrease in protein expression was concomitant with significant increases in epithelial permeability of fluorescein isothiocynate labeled-dextran 4 and 20 kDa. Analysis of focused qPCR arrays demonstrated a significant decrease in ZO-1 gene expression. Furthermore, network analysis between human TJ and antiviral response genes revealed possible interactions and regulation of TJ genes via interleukin (IL)-15 in response to HRV-1B infection. HRV-1B infection directly alters human airway epithelial TJ expression leading to increased epithelial permeability potentially via an antiviral response of IL-15.

Colloid transport in dual-permeability media

USDA-ARS?s Scientific Manuscript database

It has been widely reported that colloids can travel faster and over longer distances in natural structured porous media than in uniform structureless media used in laboratory studies. The presence of preferential pathways for colloids in the subsurface environment is of concern because of the incre...

Modeling of Permeability Structure Using Pore Pressure and Borehole Strain Monitoring

NASA Astrophysics Data System (ADS)

Kano, Y.; Ito, H.

2011-12-01

Hydraulic or transport property, especially permeability, of the rock affect the behavior of the fault during earthquake rupture and also interseismic period. The methods to determine permeability underground are hydraulic test utilizing borehole and packer or core measurement in laboratory. Another way to know the permeability around a borehole is to examine responses of pore pressure to natural loading such as barometric pressure change at surface or earth tides. Using response to natural deformation is conventional method for water resource research. The scale of measurement is different among in-situ hydraulic test, response method, and core measurement. It is not clear that the relationship between permeability values form each method for an inhomogeneous medium such as a fault zone. Supposing the measurement of the response to natural loading, we made a model calculation of permeability structure around a fault zone. The model is 2 dimensional and constructed with vertical high-permeability layer in uniform low-permeability zone. We assume the upper and lower boundaries are drained and no-flow condition. We calculated the flow and deformation of the model for step and cyclic loading by numerically solving a two-dimensional diffusion equation. The model calculation shows that the width of the high-permeability zone and contrast of the permeability between high- and low- permeability zones control the contribution of the low-permeability zone. We made a calculation with combinations of permeability and fault width to evaluate the sensitivity of the parameters to in-situ measurement of permeability. We applied the model calculation to the field results of in-situ packer test, and natural response of water level and strain monitoring carried out in the Kamioka mine. The model calculation shows that knowledge of permeability in host rock is also important to obtain permeability of fault zone itself. The model calculations help to design long-term pore pressure monitoring, in-situ hydraulic test, and core measurement using drill holes to better understand fault zone hydraulic properties.

Effect of mitochondrial apoptotic activation through the mitochondrial membrane permeability transition pore on yak meat tenderness during postmortem aging.

PubMed

Wang, Lin-Lin; Han, Ling; Ma, Xiu-Li; Yu, Qun-Li; Zhao, Suo-Nan

2017-11-01

The effect of membrane permeability transition pore dependent mitochondrial apoptotic activation on yak meat tenderness was investigated. Results indicate that MPTP opening increased significantly and the mitochondrial membrane potential decreased markedly in the early aging process (P<0.05). Cytochrome c was released from the mitochondria to the cytoplasm via the MPTP in the early period. Meanwhile, the activation of procaspase-9 occurred earlier than that of procaspase-3. Cyclosporin A suppressed the MPTP opening, depolarization of the mitochondrial membrane potential, activities of caspase-9 and caspase-3, apoptosis rate, myofibril fragmentation index, reactive oxygen species generation, and Ca 2+ levels. These results demonstrated that MPTP mediated the release of cytochrome c in the mitochondrial apoptotic pathway. Furthermore, yak meat tenderness was improved by mitochondrial apoptotic pathway during aging. MPTP opening may be influenced by the ROS generation and Ca 2+ overloading in yak meat during postmortem aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study on the apoptosis mediated by cytochrome c and factors that affect the activation of bovine longissimus muscle during postmortem aging.

PubMed

Zhang, Jiaying; Yu, Qunli; Han, Ling; Chen, Cheng; Li, Hang; Han, Guangxing

2017-06-01

This study investigates whether bovine longissimus muscle cell apoptosis occurs during postmortem aging and whether apoptosis is dependent on the mitochondria pathway. This study also determines the apoptosis process mediated by cytochrome c after its release from mitochondria and the factors that affect the activation processes. Results indicate that apoptotic nuclei were detected at 12 h postmortem. Cytochrome c release from the mitochondria to the cytoplasm activated the caspase-9 and caspase-3 at early postmortem aging and the activation of caspase-9 occurs before the activation of caspase-3. The pH level decreased during the first 48 h postmortem, whereas the mitochondria membrane permeability increased from 6 to 12 h. Results demonstrate that an apoptosis process of bovine muscle occurred during postmortem aging. Apoptosis was dependent on the mitochondria pathway and occurred at early postmortem aging. Increased mitochondria membrane permeability and low pH are necessary conditions for the release of cytochrome c during postmortem aging.

Use of plasma proteins as solubilizing agents in in vitro permeability experiments: correction for unbound drug concentration using the reciprocal permeability approach.

PubMed

Katneni, Kasiram; Charman, Susan A; Porter, Christopher J H

2008-01-01

The purpose of the present study was to explore the applicability of the reciprocal permeability approach to correct for changes in thermodynamic activity when in vitro permeability data are generated in the presence of plasma proteins. Diazepam (DIA), digoxin (DIG), and propranolol (PRO) permeability was assessed in the presence of bovine serum albumin (BSA) and bovine alpha-1-acid glycoprotein (AAG). The reciprocal permeability approach was subsequently employed to calculate the true permeability coefficient (Papp(corr)) and the operational protein association constant (nK(a)). For BSA binding, good agreement was observed between the Papp(corr) values and Papp values obtained in the absence of protein. For PRO and AAG, where binding affinity was high, deviation in the reciprocal permeability plots was evident suggesting ligand depletion at low drug/high protein concentrations. Bidirectional DIG permeability data in the presence of either BSA or AAG indicated that neither protein had an effect on the efflux transporters involved in DIG permeability. The data suggest that plasma proteins can be utilized in permeability experiments with no adverse effects on transporter function and that the reciprocal permeability approach can be used to correct permeability data for changes in unbound drug concentration. c) 2007 Wiley-Liss, Inc.

Screening and identification of potential PTP1B allosteric inhibitors using in silico and in vitro approaches.

PubMed

Shinde, Ranajit Nivrutti; Kumar, G Siva; Eqbal, Shahbaz; Sobhia, M Elizabeth

2018-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for Type 2 diabetes due to its specific role as a negative regulator of insulin signaling pathways. Discovery of active site directed PTP1B inhibitors is very challenging due to highly conserved nature of the active site and multiple charge requirements of the ligands, which makes them non-selective and non-permeable. Identification of the PTP1B allosteric site has opened up new avenues for discovering potent and selective ligands for therapeutic intervention. Interactions made by potent allosteric inhibitor in the presence of PTP1B were studied using Molecular Dynamics (MD). Computationally optimized models were used to build separate pharmacophore models of PTP1B and TCPTP, respectively. Based on the nature of interactions the target residues offered, a receptor based pharmacophore was developed. The pharmacophore considering conformational flexibility of the residues was used for the development of pharmacophore hypothesis to identify potentially active inhibitors by screening large compound databases. Two pharmacophore were successively used in the virtual screening protocol to identify potential selective and permeable inhibitors of PTP1B. Allosteric inhibition mechanism of these molecules was established using molecular docking and MD methods. The geometrical criteria values confirmed their ability to stabilize PTP1B in an open conformation. 23 molecules that were identified as potential inhibitors were screened for PTP1B inhibitory activity. After screening, 10 molecules which have good permeability values were identified as potential inhibitors of PTP1B. This study confirms that selective and permeable inhibitors can be identified by targeting allosteric site of PTP1B.

Methane hydrate induced permeability modification for multiphase flow in unsaturated porous media

NASA Astrophysics Data System (ADS)

Seol, Yongkoo; Kneafsey, Timothy J.

2011-08-01

An experimental study was performed using X-ray computed tomography (CT) scanning to capture three-dimensional (3-D) methane hydrate distributions and potential discrete flow pathways in a sand pack sample. A numerical study was also performed to develop and analyze empirical relations that describe the impacts of hydrate accumulation habits within pore space (e.g., pore filling or grain cementing) on multiphase fluid migration. In the experimental study, water was injected into a hydrate-bearing sand sample that was monitored using an X-ray CT scanner. The CT images were converted into numerical grid elements, providing intrinsic sample data including porosity and phase saturations. The impacts of hydrate accumulation were examined by adapting empirical relations into the flow simulations as additional relations governing the evolution of absolute permeability of hydrate bearing sediment with hydrate deposition. The impacts of pore space hydrate accumulation habits on fluid migration were examined by comparing numerical predictions with experimentally measured water saturation distributions and breakthrough curves. A model case with 3-D heterogeneous initial conditions (hydrate saturation, porosity, and water saturation) and pore body-preferred hydrate accumulations best captured water migration behavior through the hydrate-bearing sample observed in the experiment. In the best matching model, absolute permeability in the hydrate bearing sample does not decrease significantly with increasing hydrate saturation until hydrate saturation reaches about 40%, after which it drops rapidly, and complete blockage of flow through the sample can occur as hydrate accumulations approach 70%. The result highlights the importance of permeability modification due to hydrate accumulation habits when predicting multiphase flow through high-saturation, reservoir quality hydrate-bearing sediments.

Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice.

PubMed

Tehler, Ulrika; Fagerberg, Jonas H; Svensson, Richard; Larhed, Mats; Artursson, Per; Bergström, Christel A S

2013-03-28

Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.

VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer

PubMed Central

Gerstner, Elizabeth R.; Duda, Dan G.; di Tomaso, Emmanuelle; Ryg, Peter A.; Loeffler, Jay S.; Sorensen, A. Gregory; Ivy, Percy; Jain, Rakesh K.; Batchelor, Tracy T.

2016-01-01

Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. In addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites. PMID:19333229

Effects of ultrasound and sodium lauryl sulfate on the transdermal delivery of hydrophilic permeants: Comparative in vitro studies with full-thickness and split-thickness pig and human skin

PubMed Central

Seto, Jennifer E.; Polat, Baris E.; Lopez, Renata F.V.; Blankschtein, Daniel; Langer, Robert

2010-01-01

The simultaneous application of ultrasound and the surfactant sodium lauryl sulfate (referred to as US/SLS) to skin enhances transdermal drug delivery (TDD) in a synergistic mechanical and chemical manner. Since full-thickness skin (FTS) and split-thickness skin (STS) differ in mechanical strength, US/SLS treatment may have different effects on their transdermal transport pathways. Therefore, we evaluated STS as an alternative to the well-established US/SLS-treated FTS model for TDD studies of hydrophilic permeants. We utilized the aqueous porous pathway model to compare the effects of US/SLS treatment on the skin permeability and the pore radius of pig and human FTS and STS over a range of skin electrical resistivity values. Our findings indicate that the US/SLS-treated pig skin models exhibit similar permeabilities and pore radii, but the human skin models do not. Furthermore, the US/SLS-enhanced delivery of gold nanoparticles and quantum dots (two model hydrophilic macromolecules) is greater through pig STS than through pig FTS, due to the presence of less dermis that acts as an artificial barrier to macromolecules. In spite of greater variability in correlations between STS permeability and resistivity, our findings strongly suggest the use of 700-μm-thick pig STS to investigate the in vitro US/SLS-enhanced delivery of hydrophilic macromolecules. PMID:20346994

Oil permeability variations on lagoon sand beaches in the Patos-Guaíba system in Rio Grande do Sul, Brazil.

PubMed

Oliveira, Elaine Baroni; Nicolodi, João Luiz

2017-02-15

Permeability is the ability of a sediment deposit to allow fluids to pass through it. It depends on the local types of sediments. When the fluid is oil, high permeability implies greater interaction with the site and more extensive damage, which makes recovery most difficult. Knowledge of permeability oscillations is necessary to understand oil behavior and improve cleanup techniques. The goal is to determine oil permeability variations on lagoon sand beaches. Oil permeability tests were performed at the beach face, using a Modified Phillip Dunne Permeameter and parameters were sampled. Permeability of lagoon beaches is driven by grain diameter and roundness, soil compaction, and depth of the water table. Factors that enhance permeability include: sand sorting, vertical distribution of sediments and gravel percentage. High permeability on lagoon beaches is related to polymodal distribution, to the sediment package, and to the system's low mobility. Copyright © 2016 Elsevier Ltd. All rights reserved.

PREFERENTIAL RADON TRANSPORT THROUGH HIGHLY PERMEABLE CHANNELS IN SOILS

EPA Science Inventory

The paper discusses preferential radon transport through highly permeable channels in soils. Indoor radon levels (that can pose a serious health risk) can be dramatically increased by air that is drawn into buildings through pipe penetrations that connect to permeable channels in...

Structure and Function of Lipopolysaccharide Binding Protein

NASA Astrophysics Data System (ADS)

Schumann, Ralf R.; Leong, Steven R.; Flaggs, Gail W.; Gray, Patrick W.; Wright, Samuel D.; Mathison, John C.; Tobias, Peter S.; Ulevitch, Richard J.

1990-09-01

The primary structure of lipopolysaccharide binding protein (LBP), a trace plasma protein that binds to the lipid A moiety of bacterial lipopolysaccharides (LPSs), was deduced by sequencing cloned complementary DNA. LBP shares sequence identity with another LPS binding protein found in granulocytes, bactericidal/permeability-increasing protein, and with cholesterol ester transport protein of the plasma. LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor. The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.

Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption.

PubMed

Newby, Danielle; Freitas, Alex A; Ghafourian, Taravat

2015-01-27

Oral absorption of compounds depends on many physiological, physiochemical and formulation factors. Two important properties that govern oral absorption are in vitro permeability and solubility, which are commonly used as indicators of human intestinal absorption. Despite this, the nature and exact characteristics of the relationship between these parameters are not well understood. In this study a large dataset of human intestinal absorption was collated along with in vitro permeability, aqueous solubility, melting point, and maximum dose for the same compounds. The dataset allowed a permeability threshold to be established objectively to predict high or low intestinal absorption. Using this permeability threshold, classification decision trees incorporating a solubility-related parameter such as experimental or predicted solubility, or the melting point based absorption potential (MPbAP), along with structural molecular descriptors were developed and validated to predict oral absorption class. The decision trees were able to determine the individual roles of permeability and solubility in oral absorption process. Poorly permeable compounds with high solubility show low intestinal absorption, whereas poorly water soluble compounds with high or low permeability may have high intestinal absorption provided that they have certain molecular characteristics such as a small polar surface or specific topology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A fully-coupled discontinuous Galerkin spectral element method for two-phase flow in petroleum reservoirs

NASA Astrophysics Data System (ADS)

Taneja, Ankur; Higdon, Jonathan

2018-01-01

A high-order spectral element discontinuous Galerkin method is presented for simulating immiscible two-phase flow in petroleum reservoirs. The governing equations involve a coupled system of strongly nonlinear partial differential equations for the pressure and fluid saturation in the reservoir. A fully implicit method is used with a high-order accurate time integration using an implicit Rosenbrock method. Numerical tests give the first demonstration of high order hp spatial convergence results for multiphase flow in petroleum reservoirs with industry standard relative permeability models. High order convergence is shown formally for spectral elements with up to 8th order polynomials for both homogeneous and heterogeneous permeability fields. Numerical results are presented for multiphase fluid flow in heterogeneous reservoirs with complex geometric or geologic features using up to 11th order polynomials. Robust, stable simulations are presented for heterogeneous geologic features, including globally heterogeneous permeability fields, anisotropic permeability tensors, broad regions of low-permeability, high-permeability channels, thin shale barriers and thin high-permeability fractures. A major result of this paper is the demonstration that the resolution of the high order spectral element method may be exploited to achieve accurate results utilizing a simple cartesian mesh for non-conforming geological features. Eliminating the need to mesh to the boundaries of geological features greatly simplifies the workflow for petroleum engineers testing multiple scenarios in the face of uncertainty in the subsurface geology.

Overexpression of aryl hydrocarbon receptor (AHR) signalling pathway in human meningioma.

PubMed

Talari, Noble Kumar; Panigrahi, Manas K; Madigubba, Sailaja; Phanithi, Prakash Babu

2018-04-01

Aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor and involved in tumorigenesis of many cancers. However there are no reports on AHR in human meningioma. Therefore we examined the status of the AHR and its signalling molecules in human meningioma by using tumor biopsy samples and autopsy control meninges. We report the up regulation of AHR pathway genes like aryl hydrocarbon receptor nuclear translocator (ARNT), aldehyde dehydrogenase1family memberA3 (ALDH1A3), cytochrome P450, family1, subfamily A polypeptide1 (CYP1A1) and TCCD induced poly ADP ribose polymerase (TIPARP) gene expression in human meningioma. Further, AHR protein expression was found to be up regulated in all grades of human meningioma. We found that AHR localized in the nucleus for high grade anaplastic meningioma through immunohistochemical analysis. Since AHR signalling pathway was known to involve in inhibition of apoptosis in cancer cells, we evaluated the cyclophilin D levels which maintains mitochondrial permeability transition pore a critical event during apoptosis. We report that cyclophilin D levels were upregulated in all grades of human meningioma compared to control meninges. Finally we also evaluated c-Fos protein levels as its levels were regulated by AHR. Here we report that c-Fos protein levels were down regulated in all grades of human meningioma compared to control meninges. To sum-up we found that AHR signalling pathway components were upregulated, as the grade of the meningioma progresses from low to high grade, suggesting an important role of AHR signalling pathway in human meningioma.

Thermo-hydro-mechanical coupling in long-term sedimentary rock response

NASA Astrophysics Data System (ADS)

Makhnenko, R. Y.; Podladchikov, Y.

2017-12-01

Storage of nuclear waste or CO2 affects the state of stress and pore pressure in the subsurface and may induce large thermal gradients in the rock formations. In general, the associated coupled thermo-hydro-mechanical effect on long-term rock deformation and fluid flow have to be studied. Principles behind mathematical models for poroviscoelastic response are reviewed, and poroviscous model parameter, the bulk viscosity, is included in the constitutive equations. Time-dependent response (creep) of fluid-filled sedimentary rocks is experimentally quantified at isotropic stress states. Three poroelastic parameters are measured by drained, undrained, and unjacketed geomechanical tests for quartz-rich Berea sandstone, calcite-rich Apulian limestone, and clay-rich Jurassic shale. The bulk viscosity is calculated from the measurements of pore pressure growth under undrained conditions, which requires time scales 104 s. The bulk viscosity is reported to be on the order of 1015 Pa•s for the sandstone, limestone, and shale. It is found to be decreasing with the increase of pore pressure despite corresponding decrease in the effective stress. Additionally, increase of temperature (from 24 ºC to 40 ºC) enhances creep, where the most pronounced effect is reported for the shale with bulk viscosity decrease by a factor of 3. Viscous compaction of fluid-filled porous media allows a generation of a special type of fluid flow instability that leads to formation of high-porosity, high-permeability domains that are able to self-propagate upwards due to interplay between buoyancy and viscous resistance of the deforming porous matrix. This instability is known as "porosity wave" and its formation is possible under conditions applicable to deep CO2 storage in reservoirs and explains creation of high-porosity channels and chimneys. The reported experiments show that the formation of high-permeability pathways is most likely to occur in low-permeable clay-rich materials (caprock representatives) at elevated temperatures.

Translocation pathways for inhaled asbestos fibers

PubMed Central

Miserocchi, G; Sancini, G; Mantegazza, F; Chiappino, Gerolamo

2008-01-01

We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption) and hydraulic (interstitial pressure is subatmospheric) pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation) wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation). Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots) reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow) and in the liver (reflecting high microvascular permeability) while it is relatively low in the brain (due to low permeability of blood-brain barrier). Ultrafine fibers (length < 5 μm, diameter < 0.25 μm) can travel larger distances due to low steric hindrance (in mesothelioma about 90% of fibers are ultrafine). Fibers translocation is a slow process developing over decades of life: it is aided by high biopersistence, by inflammation-induced increase in permeability, by low steric hindrance and by fibers motion pattern at low Reynolds numbers; it is hindered by fibrosis that increases interstitial flow resistances. PMID:18218073

Seismic Signatures of Hydrothermal Pathways Along the East Pacific Rise Between 9°16' and 9°56'N

NASA Astrophysics Data System (ADS)

Marjanović, Milena; Fuji, Nobuaki; Singh, Satish C.; Belahi, Thomas; Escartín, Javier

2017-12-01

We apply wave equation-based techniques to 2-D seismic data to characterize the nature of zero-age upper crust at the East Pacific Rise from 9°16' to 9°56'N. The final velocity model reveals a number of low-velocity anomalies, complex in shape, extending down to 1 km below the seafloor. We attribute them to the presence of hydrothermal flow. Depending on their spatial correlation with the previously identified tectonic discontinuities in bathymetry and presence of venting, we classify them as downgoing and upgoing pathways, respectively. This distinction is not always clear; within the third-order discontinuities at 9°20' and 9°37'N, both pathways may be present. The region north of 9°44'N, known for its magmatic robustness and volcanic activity, is represented by five low-velocity perturbations. Three of these anomalies are spatially correlated with the fourth-order discontinuities and attributed to the presence of the on-axis recharge zones. The remaining two anomalies underlie two vent clusters, marked as hydrothermally active sites after the last documented eruption event. These velocity anomalies can be thus identified as the up-flow pathways or at least their remnants. By comparing our results to the available interdisciplinary data sets, we show that the interaction between the tectono-magmatic and hydrothermal processes is not straightforward due to different timescales at which they operate. However, for developing, maintaining, and driving vigorous, high-temperature hydrothermal flow, the high crustal permeability and high thermal regime must coexist in time and space.

Could an endoneurial endothelial crosstalk between Wnt/β-catenin and Sonic Hedgehog pathways underlie the early disruption of the infra-orbital blood-nerve barrier following chronic constriction injury?

PubMed

Moreau, Nathan; Mauborgne, Annie; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette B; Villanueva, Luis; Pohl, Michel; Boucher, Yves

2017-01-01

Blood–nerve barrier disruption is pivotal in the development of neuroinflammation, peripheral sensitization, and neuropathic pain after peripheral nerve injury. Activation of toll-like receptor 4 and inactivation of Sonic Hedgehog signaling pathways within the endoneurial endothelial cells are key events, resulting in the infiltration of harmful molecules and immunocytes within the nerve parenchyma. However, we showed in a previous study that preemptive inactivation of toll-like receptor 4 signaling or sustained activation of Sonic Hedgehog signaling did not prevent the local alterations observed following peripheral nerve injury, suggesting the implication of another signaling pathway. Using a classical neuropathic pain model, the infraorbital nerve chronic constriction injury (IoN-CCI), we investigated the role of the Wnt/β-catenin pathway in chronic constriction injury-mediated blood–nerve barrier disruption and in its interactions with the toll-like receptor 4 and Sonic Hedgehog pathways. In the IoN-CCI model versus control, mRNA expression levels and/or immunochemical detection of major Wnt/Sonic Hedgehog pathway (Frizzled-7, vascular endothelial-cadherin, Patched-1 and Gli-1) and/or tight junction proteins (Claudin-1, Claudin-5, and Occludin) readouts were assessed. Vascular permeability was assessed by sodium fluorescein extravasation. IoN-CCI induced early alterations in the vascular endothelial-cadherin/β-catenin/Frizzled-7 complex, shown to participate in local blood–nerve barrier disruption via a β-catenin-dependent tight junction protein downregulation. Wnt pathway also mediated a crosstalk between toll-like receptor 4 and Sonic Hedgehog signaling within endoneurial endothelial cells. Nevertheless, preemptive inhibition of Wnt/β-catenin signaling before IoN-CCI could not prevent the downregulation of key Sonic Hedgehog pathway readouts or the disruption of the infraorbital blood–nerve barrier, suggesting that Sonic Hedgehog pathway inhibition observed following IoN-CCI is an independent event responsible for blood–nerve barrier disruption. A crosstalk between Wnt/β-catenin- and Sonic Hedgehog-mediated signaling pathways within endoneurial endothelial cells could mediate the chronic disruption of the blood–nerve barrier following IoN-CCI, resulting in increased irreversible endoneurial vascular permeability and neuropathic pain development.

Hyper-Cross-Linked Additives that Impede Aging and Enhance Permeability in Thin Polyacetylene Films for Organic Solvent Nanofiltration.

PubMed

Cheng, Xi Quan; Konstas, Kristina; Doherty, Cara M; Wood, Colin D; Mulet, Xavier; Xie, Zongli; Ng, Derrick; Hill, Matthew R; Shao, Lu; Lau, Cher Hon

2017-04-26

Membrane materials with high permeability to solvents while rejecting dissolved contaminants are crucial to lowering the energy costs associated with liquid separations. However, the current lack of stable high-permeability materials require innovative engineering solutions to yield high-performance, thin membranes using stable polymers with low permeabilities. Poly[1-(trimethylsilyl)-1-propyne] (PTMSP) is one of the most permeable polymers but is extremely susceptible to physical aging. Despite recent developments in anti-aging polymer membranes, this research breakthrough has yet to be demonstrated on thin PTMSP films supported on porous polymer substrates, a crucial step toward commercializing anti-aging membranes for industrial applications. Here we report the development of scalable, thin film nanocomposite membranes supported on polymer substrates that are resistant to physical aging while having high permeabilities to alcohols. The selective layer is made up of PTMSP and nanoporous polymeric additives. The nanoporous additives provide additional passageways to solvents, enhancing the high permeability of the PTMSP materials further. Through intercalation of polyacetylene chains into the sub-nm pores of organic additives, physical aging in the consequent was significantly hindered in continuous long-term operation. Remarkably we also demonstrate that the additives enhance both membrane permeability and rejection of dissolved contaminants across the membranes, as ethanol permeability at 5.5 × 10 -6 L m m -2 h -1 bar -1 with 93% Rose Bengal (1017.6 g mol -1 ) rejection, drastically outperforming commercial and state-of-the-art membranes. These membranes can replace energy-intensive separation processes such as distillation, lowering operation costs in well-established pharmaceutical production processes.

Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization.

PubMed

Yang, Yang; Yin, Fangyuan; Hang, Qiyun; Dong, Xiaoliang; Chen, Jiao; Li, Ling; Cao, Peng; Yin, Zhimin; Luo, Lan

2018-01-01

Inflammation-induced injury of the endothelial barrier occurs in several pathological conditions, including atherosclerosis, ischemia, and sepsis. Endothelial cytoskeleton rearrangement is an important pathological mechanism by which inflammatory stimulation triggers an increase of vascular endothelial permeability. However, the mechanism maintaining endothelial cell barrier function against inflammatory stress is not fully understood. Glutathione S-transferase pi (GSTpi) exists in various types of cells and protects them against different stresses. In our previous study, GSTpi was found to act as a negative regulator of inflammatory responses. We used a Transwell permeability assay to test the influence of GSTpi and its transferase activity on the increase of endothelial permeability induced by tumor necrosis factor alpha (TNF-α). TNF-α-induced actin remodeling and the influence of GSTpi were observed by using laser confocal microscopy. Western blotting was used to test the influence of GSTpi on TNF-α-activated p38 mitogen-activated protein kinase (MAPK)/MK2/heat shock protein 27 (HSP27). GSTpi reduced TNF-α-induced stress fiber formation and endothelial permeability increase by restraining actin cytoskeleton rearrangement, and this reduction was unrelated to its transferase activity. We found that GSTpi inhibited p38MAPK phosphorylation by directly binding p38 and influenced downstream substrate HSP27-induced actin remodeling. GSTpi inhibited TNF-α-induced actin remodeling, stress fiber formation and endothelial permeability increase by inhibiting the p38MAPK/HSP27 signaling pathway. © 2018 The Author(s). Published by S. Karger AG, Basel.

The Effect of Excipients on the Permeability of BCS Class III Compounds and Implications for Biowaivers.

PubMed

Parr, Alan; Hidalgo, Ismael J; Bode, Chris; Brown, William; Yazdanian, Mehran; Gonzalez, Mario A; Sagawa, Kazuko; Miller, Kevin; Jiang, Wenlei; Stippler, Erika S

2016-01-01

Currently, the FDA allows biowaivers for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) compounds of the Biopharmaceutics Classification System (BCS). Scientific evidence should be provided to support biowaivers for BCS Class I and Class III (high solubility and low permeability) compounds. Data on the effects of excipients on drug permeability are needed to demonstrate that commonly used excipients do not affect the permeability of BCS Class III compounds, which would support the application of biowaivers to Class III compounds. This study was designed to generate such data by assessing the permeability of four BCS Class III compounds and one Class I compound in the presence and absence of five commonly used excipients. The permeability of each of the compounds was assessed, at three to five concentrations, with each excipient in two different models: Caco-2 cell monolayers, and in situ rat intestinal perfusion. No substantial increases in the permeability of any of the compounds were observed in the presence of any of the tested excipients in either of the models, with the exception of disruption of Caco-2 cell monolayer integrity by sodium lauryl sulfate at 0.1 mg/ml and higher. The results suggest that the absorption of these four BCS Class III compounds would not be greatly affected by the tested excipients. This may have implications in supporting biowaivers for BCS Class III compounds in general.

Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis

PubMed Central

Wilson, Katina M.; Leo, Lorie; Raimondi, Alejandro; Molkentin, Jeffery D.; Lentz, Steven R.; Di Paola, Jorge

2008-01-01

Many of the cellular responses that occur in activated platelets resemble events that take place following activation of cell-death pathways in nucleated cells. We tested the hypothesis that formation of the mitochondrial permeability transition pore (MPTP), a key signaling event during cell death, also plays a critical role in platelet activation. Stimulation of murine platelets with thrombin plus the glycoprotein VI agonist convulxin resulted in a rapid loss of mitochondrial transmembrane potential (Δψm) in a subpopulation of activated platelets. In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine platelet activation responses were altered. CypD-deficient platelets exhibited defects in phosphatidylserine externalization, high-level surface fibrinogen retention, membrane vesiculation, and procoagulant activity. Also, in CypD-deficient platelet-rich plasma, clot retraction was altered. Stimulation with thrombin plus H2O2, a known activator of MPTP formation, also increased high-level surface fibrinogen retention, phosphatidylserine externalization, and platelet procoagulant activity in a CypD-dependent manner. In a model of carotid artery photochemical injury, thrombosis was markedly accelerated in CypD-deficient mice. These results implicate CypD and the MPTP as critical regulators of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating arterial thrombosis. PMID:17989312

A Simplified Model for Multiphase Leakage through Faults with Applications for CO2 Storage

NASA Astrophysics Data System (ADS)

Watson, F. E.; Doster, F.

2017-12-01

In the context of geological CO2 storage, faults in the subsurface could affect storage security by acting as high permeability pathways which allow CO2 to flow upwards and away from the storage formation. To assess the likelihood of leakage through faults and the impacts faults might have on storage security numerical models are required. However, faults are complex geological features, usually consisting of a fault core surrounded by a highly fractured damage zone. A direct representation of these in a numerical model would require very fine grid resolution and would be computationally expensive. Here, we present the development of a reduced complexity model for fault flow using the vertically integrated formulation. This model captures the main features of the flow but does not require us to resolve the vertical dimension, nor the fault in the horizontal dimension, explicitly. It is thus less computationally expensive than full resolution models. Consequently, we can quickly model many realisations for parameter uncertainty studies of CO2 injection into faulted reservoirs. We develop the model based on explicitly simulating local 3D representations of faults for characteristic scenarios using the Matlab Reservoir Simulation Toolbox (MRST). We have assessed the impact of variables such as fault geometry, porosity and permeability on multiphase leakage rates.

Effect of pH on skin permeation enhancement of acidic drugs by l-menthol-ethanol system.

PubMed

Katayama, K; Matsui, R; Hatanaka, T; Koizumi, T

2001-09-11

The effect of pH on the skin permeation enhancement of three acidic drugs by the l-menthol-ethanol system was investigated. The total flux of acidic drugs from the system remarkably varied over the pH range 3.0-8.0, and the permeation enhancement factor depended on the system pH and drug. A skin permeation model, which consists of two permeant (unionized and ionized) species, two system (oily and aqueous) phases, and two permeation (lipid and pore) pathways, was developed. The assumptions were made that only the unionized species can distribute to the oily phase and transport via the lipid pathway. The model explained the relationship between the concentration of drug in the aqueous phase and system pH. The skin permeability data were also described by the model and permeability coefficients corresponding to the physicochemical properties of permeant were calculated for the lipid and pore pathways. The model simulation showed that the permeation of acidic drugs occurred from the aqueous phase and the oily phase acted as a reservoir. Whether the total flux increased with increase of pH was dependent on the lipophilicity of drug. These results suggest that the pH of l-menthol-ethanol system should be given attention to elicit the maximum permeation enhancement.

"Green" synthesized and coated nanaosilver alters the membrance permeability of barrier (intestinal, brain, endothelial) cells and stimulates oxidative stress pathways in neurons.

EPA Science Inventory

Nanosilver's (nanoAg) use in medical applications and consumer products is increasing. Because of this, its "green" synthesis and surface modification with beneficial coatings are desirable. Given nanoAg's potential exposure routes (e.g., dermal, intestin...

Effect of oxide films on hydrogen permeability of candidate Stirling engine heater head tube alloys

NASA Technical Reports Server (NTRS)

Schuon, S. R.; Misencik, J. A.

1981-01-01

The effect of oxide films developed in situ from CO/CO2 doped hydrogen on high pressure hydrogen permeability at 820 C was studied on N-155, A-286, IN 800, 19-9DL, Nitronic 40, HS-188, and IN 718 tubing in a Stirling materials simulator. The hydrogen permeability decreased with increasing dopant levels of CO or CO2 and corresponding decreases in oxide porosity. Minor reactive alloying elements strongly influenced permeability. At high levels of CO or CO2, a liquid oxide formed on alloys with greater than 50 percent Fe. This caused increased permeability. The oxides formed on the inside tube walls were analyzed and their effective permeabilities were calculated.

The low/high BCS permeability class boundary: physicochemical comparison of metoprolol and labetalol.

PubMed

Zur, Moran; Gasparini, Marisa; Wolk, Omri; Amidon, Gordon L; Dahan, Arik

2014-05-05

Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability class boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability class reference drug. Labetalol's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5-7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol-buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitro PAMPA permeability assay. The results of the in vivo perfusion studies in rats lay between the two contradictory in vitro studies; metoprolol was shown to have moderately higher rat intestinal permeability than labetalol. Theoretical distribution of the ionic species of the drugs was in corroboration with the experimental in vitro and the in vivo data. We propose three characteristics that the optimal permeability class reference drug should exhibit: (1) fraction dose absorbed in the range of 90%; (2) the optimal marker drug should be absorbed largely via passive transcellular permeability, with no/negligible carrier-mediated active intestinal transport (influx or efflux); and (3) the optimal marker drug should preferably be nonionizable. The data presented in this paper demonstrate that neither metoprolol nor labetalol can be regarded as optimal low/high-permeability class boundary standard. While metoprolol is too conservative due to its complete absorption, labetalol has been shown to be a substrate for P-gp-mediated efflux transport, and both drugs exhibit significant segmental-dependent permeability along the gastrointestinal tract. Nevertheless, the use of metoprolol as the marker compound does not carry a risk of bioinequivalence: Peff value similar to or higher than metoprolol safely indicates high-permeability classification. On the other hand, a more careful data analysis is needed if labetalol is used as the reference compound.

Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors

PubMed Central

2014-01-01

Background Small membrane-permeable molecules are now widely used during maintenance and differentiation of embryonic stem cells of different species. In particular the glycogen synthase kinase 3 (GSK3) is an interesting target, since its chemical inhibition activates the Wnt/beta-catenin pathway. In the present comparative study four GSK3 inhibitors were characterized. Methods Cytotoxicity and potential to activate the Wnt/beta-catenin pathway were tested using the commonly used GSK3 inhibitors BIO, SB-216763, CHIR-99021, and CHIR-98014. Wnt/beta-catenin-dependent target genes were measured by quantitative PCR to confirm the Wnt-reporter assay and finally EC50-values were calculated. Results CHIR-99021 and SB-216763 had the lowest toxicities in mouse embryonic stem cells and CHIR-98014 and BIO the highest toxicities. Only CHIR-99021 and CHIR-98014 lead to a strong induction of the Wnt/beta-catenin pathway, whereas BIO and SB-216763 showed a minor or no increase in activation of the Wnt/beta-catenin pathway over the natural ligand Wnt3a. The data from the Wnt-reporter assay were confirmed by gene expression analysis of the TCF/LEF regulated gene T. Conclusions Out of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity. PMID:24779365

Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors.

PubMed

Naujok, Ortwin; Lentes, Jana; Diekmann, Ulf; Davenport, Claudia; Lenzen, Sigurd

2014-04-29

Small membrane-permeable molecules are now widely used during maintenance and differentiation of embryonic stem cells of different species. In particular the glycogen synthase kinase 3 (GSK3) is an interesting target, since its chemical inhibition activates the Wnt/beta-catenin pathway. In the present comparative study four GSK3 inhibitors were characterized. Cytotoxicity and potential to activate the Wnt/beta-catenin pathway were tested using the commonly used GSK3 inhibitors BIO, SB-216763, CHIR-99021, and CHIR-98014. Wnt/beta-catenin-dependent target genes were measured by quantitative PCR to confirm the Wnt-reporter assay and finally EC50-values were calculated. CHIR-99021 and SB-216763 had the lowest toxicities in mouse embryonic stem cells and CHIR-98014 and BIO the highest toxicities. Only CHIR-99021 and CHIR-98014 lead to a strong induction of the Wnt/beta-catenin pathway, whereas BIO and SB-216763 showed a minor or no increase in activation of the Wnt/beta-catenin pathway over the natural ligand Wnt3a. The data from the Wnt-reporter assay were confirmed by gene expression analysis of the TCF/LEF regulated gene T. Out of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity.

Group boundary permeability moderates the effect of a dependency meta-stereotype on help-seeking behaviour.

PubMed

Zhang, Lange; Kou, Yu; Zhao, Yunlong; Fu, Xinyuan

2016-08-01

Previous studies have found that when low-status group members are aware that their in-group is stereotyped as dependent by a specific out-group (i.e. a dependency meta-stereotype is salient), they are reluctant to seek help from the high-status out-group to avoid confirming the negative meta-stereotype. However, it is unclear whether low-status group members would seek more help in the context of a salient dependency meta-stereotype when there is low (vs. high) group boundary permeability. Therefore, we conducted two experiments to examine the moderating effect of permeability on meta-stereotype confirmation with a real group. In study 1, we manipulated the salience of the dependency meta-stereotype, measured participants' perceived permeability and examined their help-seeking behaviour in a real-world task. Participants who perceived low permeability sought more help when the meta-stereotype was salient (vs. not salient), whereas participants who perceived high permeability sought the same amount of help across conditions. In study 2, we manipulated the permeability levels and measured the dependency meta-stereotype. Participants who endorsed a high-dependency meta-stereotype sought more help than participants who endorsed a low-dependency meta-stereotype; this effect was particularly strong in the low-permeability condition. The implications of these results for social mobility and intergroup helping are discussed. © 2015 International Union of Psychological Science.

Development of a Digital Aquifer Permeability Map for the ...

EPA Pesticide Factsheets

Researchers at the U.S. Environmental Protection Agency’s Western Ecology Division have been developing hydrologic landscape maps for selected U.S. states in an effort to create a method to identify the intrinsic watershed attributes of landscapes in regions with little data. Each hydrologic landscape unit is assigned a categorical value from five key indices of macro-scale hydrologic behavior, including annual climate, climate seasonality, aquifer permeability, terrain, and soil permeability. The aquifer permeability index requires creation of a from-scratch dataset for each state. The permeability index for the Pacific Southwest (California, Nevada, and Arizona) expands and modifies the permeability index for the Pacific Northwest (Oregon, Washington, and Idaho), which preceded it. The permeability index was created by assigning geologic map units to one of 18 categories with presumed similar values of permeability to create a hydrolithologic map. The hydrolithologies were then further categorized into permeability index classifications of high, low, unknown and surface water. Unconsolidated, carbonate, volcanic, and undifferentiated units are classified more conservatively to better address uncertainty in source data. High vs. low permeability classifications are assigned qualitatively but follow a threshold guideline of 8.5x10-2 m/day hydraulic conductivity. Estimates of permeability from surface lithology is the current best practice for broad-sca

Non-monotonic permeability variation during colloidal transport: Governing equations and analytical model

NASA Astrophysics Data System (ADS)

Chequer, L.; Russell, T.; Behr, A.; Genolet, L.; Kowollik, P.; Badalyan, A.; Zeinijahromi, A.; Bedrikovetsky, P.

2018-02-01

Permeability decline associated with the migration of natural reservoir fines impairs the well index of injection and production wells in aquifers and oilfields. In this study, we perform laboratory corefloods using aqueous solutions with different salinities in engineered rocks with different kaolinite content, yielding fines migration and permeability alteration. Unusual permeability growth has been observed at high salinities in rocks with low kaolinite concentrations. This has been attributed to permeability increase during particle detachment and re-attachment of already mobilised fines by electrostatic attraction to the rock in stagnant zones of the porous space. We refine the traditional model for fines migration by adding mathematical expressions for the particle re-attachment rate, particle detachment with delay relative to salinity decrease, and the attached-concentration-dependency of permeability. A one-dimensional flow problem that accounts for those three effects allows for an exact analytical solution. The modified model captures the observed effect of permeability increase at high water salinities in rocks with low kaolinite concentrations. The developed model matches the coreflooding data with high accuracy, and the obtained model coefficients vary within their usual intervals.

The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract.

PubMed

Zur, Moran; Cohen, Noa; Agbaria, Riad; Dahan, Arik

2015-07-15

The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability class boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol's jejunal permeability. We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form. Copyright © 2015 Elsevier B.V. All rights reserved.

Predicting A Drug'S Membrane Permeability: Evolution of a Computational Model Validated with in Vitro Permeability Assay Data

DOE PAGES

Carpenter, Timothy S.; McNerney, M. Windy; Be, Nicholas A.; ...

2016-02-16

Membrane permeability is a key property to consider in drug design, especially when the drugs in question need to cross the blood-brain barrier (BBB). A comprehensive in vivo assessment of the BBB permeability of a drug takes considerable time and financial resources. A current, simplified in vitro model to investigate drug permeability is a Parallel Artificial Membrane Permeability Assay (PAMPA) that generally provides higher throughput and initial quantification of a drug's passive permeability. Computational methods can also be used to predict drug permeability. Our methods are highly advantageous as they do not require the synthesis of the desired drug, andmore » can be implemented rapidly using high-performance computing. In this study, we have used umbrella sampling Molecular Dynamics (MD) methods to assess the passive permeability of a range of compounds through a lipid bilayer. Furthermore, the permeability of these compounds was comprehensively quantified using the PAMPA assay to calibrate and validate the MD methodology. And after demonstrating a firm correlation between the two approaches, we then implemented our MD method to quantitatively predict the most permeable potential drug from a series of potential scaffolds. This permeability was then confirmed by the in vitro PAMPA methodology. Therefore, in this work we have illustrated the potential that these computational methods hold as useful tools to help predict a drug's permeability in a faster and more cost-effective manner. Release number: LLNL-ABS-677757.« less

Predicting A Drug'S Membrane Permeability: Evolution of a Computational Model Validated with in Vitro Permeability Assay Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, Timothy S.; McNerney, M. Windy; Be, Nicholas A.

Membrane permeability is a key property to consider in drug design, especially when the drugs in question need to cross the blood-brain barrier (BBB). A comprehensive in vivo assessment of the BBB permeability of a drug takes considerable time and financial resources. A current, simplified in vitro model to investigate drug permeability is a Parallel Artificial Membrane Permeability Assay (PAMPA) that generally provides higher throughput and initial quantification of a drug's passive permeability. Computational methods can also be used to predict drug permeability. Our methods are highly advantageous as they do not require the synthesis of the desired drug, andmore » can be implemented rapidly using high-performance computing. In this study, we have used umbrella sampling Molecular Dynamics (MD) methods to assess the passive permeability of a range of compounds through a lipid bilayer. Furthermore, the permeability of these compounds was comprehensively quantified using the PAMPA assay to calibrate and validate the MD methodology. And after demonstrating a firm correlation between the two approaches, we then implemented our MD method to quantitatively predict the most permeable potential drug from a series of potential scaffolds. This permeability was then confirmed by the in vitro PAMPA methodology. Therefore, in this work we have illustrated the potential that these computational methods hold as useful tools to help predict a drug's permeability in a faster and more cost-effective manner. Release number: LLNL-ABS-677757.« less

Mechanisms of intestinal barrier dysfunction in sepsis

PubMed Central

Yoseph, Benyam P.; Klingensmith, Nathan J.; Liang, Zhe; Breed, Elise R.; Burd, Eileen M.; Mittal, Rohit; Dominguez, Jessica A.; Petrie, Benjamin; Ford, Mandy L.; Coopersmith, Craig M.

2016-01-01

Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 hours later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at six to 12 hours. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13 and 15, JAM-A, occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 hours after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 hour after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis induce a significant increase in intestinal permeability mediated through a common pathway involving alterations in claudin 2, claudin 5, JAM-A and occludin although model-specific differences in ZO-1 were also identified. PMID:27299587

Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

PubMed

Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

2016-07-01

Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis induce a significant increase in intestinal permeability mediated through a common pathway involving alterations in claudin 2, claudin 5, JAM-A, and occludin although model-specific differences in ZO-1 were also identified.

Porous zirconia ceramic as an alternative to dentin for in vitro dentin barriers cytotoxicity test.

PubMed

Hu, Meng-Long; Lin, Hong; Jiang, Ruo-Dan; Dong, Li-Min; Huang, Lin; Zheng, Gang

2018-06-01

This study assessed the potential of porous zirconia ceramic as an alternative to dentin via an in vitro dentin barrier cytotoxicity test. The permeability of dentin and porous zirconia ceramic was measured using a hydraulic-conductance system, and their permeability was divided into two groups: high and low. Using an in vitro dentin barrier test, the cytotoxicity of dental materials by dentin and porous zirconia ceramic was compared within the same permeability group. The L-929 cell viability was assessed by MTT assay. The mean (SD) permeability of the high and low group for dentin was 0.334 (0.0873) and 0.147 (0.0377) μl min -1  cm -2  cm H 2 O -1 and for zirconia porous ceramic was 0.336 (0.0609) and 0.146 (0.0340) μl min -1  cm -2  cm H 2 O -1 . The cell viability of experimental groups which are the low permeability group was higher than that of the high permeability group for both dentin and porous zirconia ceramic as a barrier except for Maxcem Elite ™ by porous zirconia ceramic. There was no significant difference between dentin and porous zirconia ceramic in cell viability, within either the high or low permeability group for all materials. The SD for cell viability of the porous zirconia ceramic was less than that of the dentin, across all materials within each permeability group, except for Maxcem Elite ™ in the high permeability group. Porous zirconia ceramic, having similar permeability to dentin at the same thickness, can be used as an alternative to dentin for in vitro dentin barrier cytotoxicity tests. In vitro dentin barrier cytotoxicity tests when a standardized porous zirconia ceramic was used as a barrier could be useful for assessing the potential toxicity of new dental materials applied to dentin before applying in clinical and may resolve the issue of procuring human teeth when testing proceeds.

Segmental-dependent permeability throughout the small intestine following oral drug administration: Single-pass vs. Doluisio approach to in-situ rat perfusion.

PubMed

Lozoya-Agullo, Isabel; Zur, Moran; Beig, Avital; Fine, Noa; Cohen, Yael; González-Álvarez, Marta; Merino-Sanjuán, Matilde; González-Álvarez, Isabel; Bermejo, Marival; Dahan, Arik

2016-12-30

Intestinal drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of drug following oral administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was assessed in three small intestinal regions: the upper jejunum, mid-small intestine, and the terminal ileum, using both the SPIP and the Doluisio experimental methods. Excellent correlation was evident between the two approaches, especially in the upper jejunum (R 2 =0.95). Significant regional-dependent permeability was found in half of drugs studied, illustrating the importance and relevance of segmental-dependent intestinal permeability. Despite the differences between the two methods, highly comparable results were obtained by both methods, especially in the medium-high P eff range. In conclusion, the SPIP and the Doluisio method are both equally useful in obtaining crucial segmental-dependent intestinal permeability data. Copyright © 2016 Elsevier B.V. All rights reserved.

Digital Rock Physics Aplications: Visualisation Complex Pore and Porosity-Permeability Estimations of the Porous Sandstone Reservoir

NASA Astrophysics Data System (ADS)

Handoyo; Fatkhan; Del, Fourier

2018-03-01

Reservoir rock containing oil and gas generally has high porosity and permeability. High porosity is expected to accommodate hydrocarbon fluid in large quantities and high permeability is associated with the rock’s ability to let hydrocarbon fluid flow optimally. Porosity and permeability measurement of a rock sample is usually performed in the laboratory. We estimate the porosity and permeability of sandstones digitally by using digital images from μCT-Scan. Advantages of the method are non-destructive and can be applied for small rock pieces also easily to construct the model. The porosity values are calculated by comparing the digital image of the pore volume to the total volume of the sandstones; while the permeability values are calculated using the Lattice Boltzmann calculations utilizing the nature of the law of conservation of mass and conservation of momentum of a particle. To determine variations of the porosity and permeability, the main sandstone samples with a dimension of 300 × 300 × 300 pixels are made into eight sub-cubes with a size of 150 × 150 × 150 pixels. Results of digital image modeling fluid flow velocity are visualized as normal velocity (streamline). Variations in value sandstone porosity vary between 0.30 to 0.38 and permeability variations in the range of 4000 mD to 6200 mD. The results of calculations show that the sandstone sample in this research is highly porous and permeable. The method combined with rock physics can be powerful tools for determining rock properties from small rock fragments.

Regional-dependent intestinal permeability and BCS classification: elucidation of pH-related complexity in rats using pseudoephedrine.

PubMed

Fairstein, Moran; Swissa, Rotem; Dahan, Arik

2013-04-01

Based on its lower Log P value relative to metoprolol, a marker for the low/high-permeability (P(eff)) class boundary, pseudoephedrine was provisionally classified as BCS low-permeability compound. On the other hand, following oral administration, pseudoephedrine fraction dose absorbed (F(abs)) and systemic bioavailability approaches 100%. This represents a challenge to the generally recognized P(eff)-F(abs) correlation. The purpose of this study was to elucidate the underlying mechanisms behind the confusion in pseudoephedrine's BCS classification. Pseudoephedrine's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Pseudoephedrine was found to be unequivocally a high-solubility compound. All of the permeability studies revealed similar phenomenon; at any given intestinal segment/pH, the permeability of metoprolol was higher than that of pseudoephedrine, however, as the intestinal region becomes progressively distal, and the pH gradually increases, pseudoephedrine's permeability rises above that of metoprolol in the former segment. This unique permeability pattern likely explains pseudoephedrine's complete absorption. In conclusion, pseudoephedrine is a BCS Class I compound; no discrepancy between P(eff) and F(abs) is involved in its absorption. Rather, it reflects the complexity behind P(eff) when considering the whole of the intestine. We propose to allow high-permeability classification to drugs with P(eff) that matches/exceeds the low/high class benchmark anywhere throughout the intestinal tract and not restricted necessarily to the jejunum.

The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-beta, increases podocyte motility and albumin permeability.

PubMed

Lee, Eun Young; Chung, Choon Hee; Khoury, Charbel C; Yeo, Tet Kin; Pyagay, Petr E; Wang, Amy; Chen, Sheldon

2009-07-01

The role of monocyte chemoattractant protein-1 (MCP-1) in diabetic nephropathy is typically viewed through the lens of inflammation, but MCP-1 might exert noninflammatory effects on the kidney cells directly. Glomerular podocytes in culture, verified to express the marker nephrin, were exposed to diabetic mediators such as high glucose or angiotensin II and assayed for MCP-1. Only transforming growth factor-beta (TGF-beta) significantly increased MCP-1 production, which was prevented by SB431542 and LY294002, indicating that signaling proceeded through the TGF-beta type I receptor kinase and the phosphatidylinositol 3-kinase pathway. The TGF-beta-induced MCP-1 was found to activate the podocyte's cysteine-cysteine chemokine receptor 2 (CCR2) and, as a result, enhance the cellular motility, cause rearrangement of the actin cytoskeleton, and increase podocyte permeability to albumin in a Transwell assay. The preceding effects of TGF-beta were replicated by treatment with recombinant MCP-1 and blocked by a neutralizing anti-MCP-1 antibody or a specific CCR2 inhibitor, RS102895. In conclusion, this is the first description that TGF-beta signaling through PI3K induces the podocyte expression of MCP-1 that can then operate via CCR2 to increase cellular migration and alter albumin permeability characteristics. The pleiotropic effects of MCP-1 on the resident kidney cells such as the podocyte may exacerbate the disease process of diabetic albuminuria.

Association between water and carbon dioxide transport in leaf plasma membranes: assessing the role of aquaporins.

PubMed

Zhao, Manchun; Tan, Hwei-Ting; Scharwies, Johannes; Levin, Kara; Evans, John R; Tyerman, Stephen D

2017-06-01

The role of some aquaporins as CO 2 permeable channels has been controversial. Low CO 2 permeability of plant membranes has been criticized because of unstirred layers and other limitations. Here we measured both water and CO 2 permeability (P os , P CO2 ) using stopped flow on plasma membrane vesicles (pmv) isolated from Pisum sativum (pea) and Arabidopsis thaliana leaves. We excluded the chemical limitation of carbonic anhydrase (CA) in the vesicle acidification technique for P CO2 using different temperatures and CA concentrations. Unstirred layers were excluded based on small vesicle size and the positive correlation between vesicle diameter and P CO2 . We observed high aquaporin activity (P os 0.06 to 0.22 cm s -1 ) for pea pmv based on all the criteria for their function using inhibitors and temperature dependence. Inhibitors of P os did not alter P CO2 . P CO2 ranged from 0.001 to 0.012 cm s -1 (mean 0.0079 + 0.0007 cm s -1 ) with activation energy of 30.2 kJ mol -1 . Intrinsic variation between pmv batches from normally grown or stressed plants revealed a weak (R 2  = 0.27) positive linear correlation between P os and P CO2 . Despite the low P CO2 , aquaporins may facilitate CO 2 transport across plasma membranes, but probably via a different pathway than for water. © 2016 John Wiley & Sons Ltd.

Permeability Changes of Integrin-Containing Multivesicular Structures Triggered by Picornavirus Entry

PubMed Central

Soonsawad, Pan; Weerachatyanukul, Wattana; Rintanen, Nina; Espinoza, Juan; McNerney, Gregory; Marjomäki, Varpu; Cheng, R. Holland

2014-01-01

Cellular uptake of clustered α2β1-integrin induces the formation of membrane compartments that subsequently mature into a multivesicular body (MVB). Enhanced internalization mediated by clustered integrins was observed upon infection by the picornavirus echovirus 1 (EVI). We elucidated the structural features of virus-induced MVBs (vMVBs) in comparison to antibody-induced control MVBs (mock infection) by means of high-pressure cryo fixation of cells followed by immuno electron tomography during early entry of the virus. Three-dimensional tomograms revealed a marked increase in the size and complexity of these vMVBs and the intraluminal vesicles (ILVs) at 2 and 3.5 hours post infection (p.i.), in contrast to the control MVBs without virus. Breakages in the membranes of vMVBs were detected from tomograms after 2 and especially after 3.5 h suggesting that these breakages could facilitate the genome release to the cytoplasm. The in situ neutral-red labeling of viral genome showed that virus uncoating starts as early as 30 min p.i., while an increase of permeability was detected in the vMVBs between 1 and 3 hours p.i., based on a confocal microscopy assay. Altogether, the data show marked morphological changes in size and permeability of the endosomes in the infectious entry pathway of this non-enveloped enterovirus and suggest that the formed breakages facilitate the transfer of the genome to the cytoplasm for replication. PMID:25299706

A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide

PubMed Central

Klaiber, Michael; Dankworth, Beatrice; Kruse, Martin; Hartmann, Michael; Nikolaev, Viacheslav O.; Yang, Ruey-Bing; Völker, Katharina; Gaßner, Birgit; Oberwinkler, Heike; Feil, Robert; Freichel, Marc; Groschner, Klaus; Skryabin, Boris V.; Frantz, Stefan; Birnbaumer, Lutz; Pongs, Olaf; Kuhn, Michaela

2011-01-01

Cardiac atrial natriuretic peptide (ANP) regulates arterial blood pressure, moderates cardiomyocyte growth, and stimulates angiogenesis and metabolism. ANP binds to the transmembrane guanylyl cyclase (GC) receptor, GC-A, to exert its diverse functions. This process involves a cGMP-dependent signaling pathway preventing pathological [Ca2+]i increases in myocytes. In chronic cardiac hypertrophy, however, ANP levels are markedly increased and GC-A/cGMP responses to ANP are blunted due to receptor desensitization. Here we show that, in this situation, ANP binding to GC-A stimulates a unique cGMP-independent signaling pathway in cardiac myocytes, resulting in pathologically elevated intracellular Ca2+ levels. This pathway involves the activation of Ca2+‐permeable transient receptor potential canonical 3/6 (TRPC3/C6) cation channels by GC-A, which forms a stable complex with TRPC3/C6 channels. Our results indicate that the resulting cation influx activates voltage-dependent L-type Ca2+ channels and ultimately increases myocyte Ca2+i levels. These observations reveal a dual role of the ANP/GC-A–signaling pathway in the regulation of cardiac myocyte Ca2+i homeostasis. Under physiological conditions, activation of a cGMP-dependent pathway moderates the Ca2+i-enhancing action of hypertrophic factors such as angiotensin II. By contrast, a cGMP-independent pathway predominates under pathophysiological conditions when GC-A is desensitized by high ANP levels. The concomitant rise in [Ca2+]i might increase the propensity to cardiac hypertrophy and arrhythmias. PMID:22027011

Sharp Permeability Transitions due to Shallow Diagenesis of Subduction Zone Sediments

NASA Astrophysics Data System (ADS)

James, S.; Screaton, E.

2013-12-01

The permeability of hemipelagic sediments is an important factor in fluid flow in subduction zones and can be affected by porosity changes and cementation-dissolution processes acting during diagenesis. Anomalously high porosities have been observed in cores from the Shikoku Basin sediments approaching the Nankai Trough subduction zone. These high porosities have been attributed to the presence of minor amounts of amorphous silica cement that strengthen the sediment and inhibit consolidation. The porosity rapidly drops from 66-68% to 54-56% at a diagenetic boundary where the amorphous silica cement dissolves. Although the anomalous porosity profiles at Nankai have received attention, the magnitude of the corresponding permeability change has not been addressed. In this study, permeability profiles were constructed using permeability-porosity relationships from previous studies, to estimate the magnitude and rate of permeability changes with depth. The predicted permeability profiles for the Nankai Trough sediment cores indicate that permeability drops by almost one order of magnitude across the diagenetic boundary. This abrupt drop in permeability has the potential to facilitate significant changes in pore fluid pressures and thus to influence the deformation of the sediment onto the accretionary prism. At the Costa Rica subduction zone, results vary with location. Site U1414 offshore the Osa Peninsula shows porosities stable at 69% above 145 mbsf and then decrease to 54% over a 40 m interval. A porosity drop of that magnitude is predicted to correlate to an order of magnitude permeability decrease. In contrast, porosity profiles from Site 1039 offshore the Nicoya Peninsula and Site U1381 offshore the Osa Peninsula show anomalously high porosities but no sharp drop. It is likely that sediments do not cross the diagenetic boundary due to the extremely low (<10°C/km) thermal gradient at Site 1039 and the thin (<100 m) sediment cover at Site U1381. At these locations, the porosity loss and permeability reduction may occur after the sediment is subducted and contribute to high pore pressures at the plate boundary.

EETs reduces LPS-induced hyperpermeability by targeting GRP78 mediated Src activation and subsequent Rho/ROCK signaling pathway

PubMed Central

Dong, Ruolan; Hu, Danli; Yang, Yan; Chen, Zhihui; Fu, Menglu; Wang, Dao Wen; Xu, Xizhen; Tu, Ling

2017-01-01

Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice. In addition, sEH inhibitor AUDA and 11,12-EET also decreased endothelial hyper-permeability in the in-vitro study. Importantly, the relative mechanisms were associated with reduced GRP78-Src interaction and ROS production, and subsequently reduced RhoA/ROCK activation, and eventually decreased VE-cadherin and myosin light chain (MLC) phosphorylation. Thus CYP2J2-EETs is crucial for RhoA-dependent regulation of cytoskeletal architecture leading to reversible changes in vascular permeability, which may contribute to the development of new therapeutic approaches for pulmonary edema and other diseases caused by abnormal vascular permeability. PMID:28881620

Roles of Ion Channels in the Environmental Responses of Plants

NASA Astrophysics Data System (ADS)

Furuichi, Takuya; Kawano, Tomonori; Tatsumi, Hitoshi; Sokabe, Masahiro

When plant cells are exposed to environmental stresses or perceive internal signal molecules involved in growth and development, ion channels are transiently activated to convert these stimuli into intracellular signals. Among the ions taken up by plant cells, Ca2+ plays an essential role as an intracellular second messenger in plants; the cytoplasmic free Ca2+ concentration ([Ca2+]c) is therefore strictly regulated. Signal transduction pathways mediated by changes in [Ca2+]c - termed Ca2+ signaling - are initiated by the activation of Ca2+-permeable channels in many cases. To date, a large body of electrophysiological and recent molecular biological studies have revealed that plants possess Ca2+ channels belonging to distinct types with different gating mechanisms, and a variety of genes for Ca2+-permeable channels have been isolated and functionally characterized. Topics in this chapter focus on long-distance signal translocation in plants and the characteristics of a variety of plant Ca2+-permeable channels including voltage-dependent Ca2+-permeable channels, cyclic nucleotide-gated cation channels, ionotropic glutamate receptors and mechanosensitive channels. We discuss their roles in environmental responses and in the regulation of growth and development.

Apparatus and process for water treatment

DOEpatents

Phifer, Mark A.; Nichols, Ralph L.

2001-01-01

An apparatus is disclosed utilizing permeable treatment media for treatment of contaminated water, along with a method for enhanced passive flow of contaminated water through the treatment media. The apparatus includes a treatment cell including a permeable structure that encloses the treatment media, the treatment cell may be located inside a water collection well, exterior to a water collection well, or placed in situ within the pathway of contaminated groundwater. The passive flow of contaminated water through the treatment media is maintained by a hydraulic connection between a collecting point of greater water pressure head, and a discharge point of lower water pressure head. The apparatus and process for passive flow and groundwater treatment utilizes a permeable treatment media made up of granular metal, bimetallics, granular cast iron, activated carbon, cation exchange resins, and/or additional treatment materials. An enclosing container may have an outer permeable wall for passive flow of water into the container and through the enclosed treatment media to an effluent point. Flow of contaminated water is attained without active pumping of water through the treatment media. Remediation of chlorinated hydrocarbons and other water contaminants to acceptable regulatory concentration levels is accomplished without the costs of pumping, pump maintenance, and constant oversight by personnel.

A Mathematical Model of Solute Coupled Water Transport in Toad Intestine Incorporating Recirculation of the Actively Transported Solute

PubMed Central

Larsen, Erik Hviid; Sørensen, Jakob Balslev; Sørensen, Jens Nørkær

2000-01-01

A mathematical model of an absorbing leaky epithelium is developed for analysis of solute coupled water transport. The non-charged driving solute diffuses into cells and is pumped from cells into the lateral intercellular space (lis). All membranes contain water channels with the solute passing those of tight junction and interspace basement membrane by convection-diffusion. With solute permeability of paracellular pathway large relative to paracellular water flow, the paracellular flux ratio of the solute (influx/outflux) is small (2–4) in agreement with experiments. The virtual solute concentration of fluid emerging from lis is then significantly larger than the concentration in lis. Thus, in absence of external driving forces the model generates isotonic transport provided a component of the solute flux emerging downstream lis is taken up by cells through the serosal membrane and pumped back into lis, i.e., the solute would have to be recirculated. With input variables from toad intestine (Nedergaard, S., E.H. Larsen, and H.H. Ussing, J. Membr. Biol. 168:241–251), computations predict that 60–80% of the pumped flux stems from serosal bath in agreement with the experimental estimate of the recirculation flux. Robust solutions are obtained with realistic concentrations and pressures of lis, and with the following features. Rate of fluid absorption is governed by the solute permeability of mucosal membrane. Maximum fluid flow is governed by density of pumps on lis-membranes. Energetic efficiency increases with hydraulic conductance of the pathway carrying water from mucosal solution into lis. Uphill water transport is accomplished, but with high hydraulic conductance of cell membranes strength of transport is obscured by water flow through cells. Anomalous solvent drag occurs when back flux of water through cells exceeds inward water flux between cells. Molecules moving along the paracellular pathway are driven by a translateral flow of water, i.e., the model generates pseudo-solvent drag. The associated flux-ratio equation is derived. PMID:10919860

Fracture propagation and fluid transport in palaeogeothermal fields and man-made reservoirs in limestone

NASA Astrophysics Data System (ADS)

Philipp, S. L.; Reyer, D.; Meier, S.

2009-04-01

Geothermal reservoirs are rock units from which the internal heat can be extracted using water as a transport means in an economically efficient manner. In geothermal reservoirs in limestone (and similar in other rocks with low matrix permeability), fluid flow is largely, and may be almost entirely, controlled by the permeability of the fracture network. No flow, however, takes place along a particular fracture network unless the fractures are interconnected. For fluid flow to occur from one site to another there must be at least one interconnected cluster of fractures that links these sites (the percolation threshold must be reached). In order to generate permeability in man-made reservoirs, interconnected fracture systems are formed either by creating hydraulic fractures or by massive hydraulic stimulation of the existing fracture system in the host rock. For effective stimulation, the geometry of the fracture system and the mechanical properties of the host rock (particularly rock stiffnesses and strengths) must be known. Here we present results of a study of fracture systems in rocks that could be used to host man-made geothermal reservoirs: the Muschelkalk (Middle Triassic) limestones in Germany. Studies of fracture systems in exposed palaeogeothermal fields can also help understand the permeability development in stimulated reservoirs. We therefore present data on the infrastructures of extinct fracture-controlled geothermal fields in fault zones in the Blue Lias (Lower Jurassic), Great Britain. In fault zones there are normally two main mechanical and hydrogeological units. The fault core, along which fault slip mostly occurs, consists mainly of breccia and other cataclastic rocks. The fault damage zone comprises numerous fractures of various sizes. During fault slip, the fault core may transport water (if its orientation is favourable to the hydraulic gradient in the area). In the damage zone, however, fluid transport through fracture networks depends particularly on the current local stress field. One reason for this is that fractures are sensitive to changes in the stress field and deform much more easily than circular pores. If the maximum horizontal compression is oriented perpendicular to the fault strike, its fractures (mainly in the damage zone) tend to be closed and lead less water than if the maximum horizontal compression is oriented parallel to the fault strike, in which case its fractures tend to open up and be favourable to fluid transport. In areas of potential geothermal reservoirs, fault zones must be studied, keeping in mind that the permeability structure of a fault zone depends partly on the mechanical units of the fault zone and partly on the local stress field. To explore stress fields affecting fracture propagation we have run numerical models using the finite-element and the boundary-element methods. We focus on the influence of changes in mechanical properties (particularly Young's modulus) between host rock layers in geothrmal reservoirs in limestone. The numerical models show that stresses commonly concentrate in stiff layers. Also, at the contacts between soft marl and stiffer limestone layers, the stress trajectories (directions of the principal stresses) may become rotated. Depending on the external loading conditions, certain layers may become stress barriers to fracture propagation. In a reservoir where most hydrofractures become stratabound (confined to individual layers), interconnected fracture systems are less likely to develop than in one with non-stratabound hydrofractures. Reservoirs with stratabound fractures may not reach the percolation threshold needed for significant permeability. We also used the field data to investigate the fracture-related permeability of fluid reservoirs in limestone with numerical models. We simulated different scenarios, in which potential fluid pathways were added successively (vertical extension fractures, inclined shear fractures and open layer contacts). Short and straight fluid pathways parallel to the flow direction lead to the highest permeabilities. The better the connectivity of the fracture system, the higher is the resulting permeability. Only in well-interconnected, continuous systems of fluid pathways there is a correlation between the apertures of the fractures and the permeability. Our results suggest that fluid transport along faults, and the propagation and aperture variation of hydrofractures, are important parameters in the permeability development of geothermal reservoirs. These studies provide a basis for models of fracture networks and fluid transport in future man-made reservoirs. We conclude that the likely permeability of a man-made geothermal reservoir can be inferred from field data, natural analogues, laboratory measurements, and numerical models.

Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

PubMed

Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

2013-07-18

The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

Atorvastatin prevents angiotensin II-induced high permeability of human arterial endothelial cell monolayers via ROCK signaling pathway.

PubMed

Yi, Ren; Xiao-Ping, Gao; Hui, Liang

2015-03-27

Intracranial aneurysm, as a common cause of cerebral hemorrhage, is often discovered when the aneurysm ruptures, causing subarachnoid hemorrhage. Unfortunately, the formation of cerebral aneurysm, which is associated with endothelial damage and macrophage migration, still cannot be prevented now. Tight junctions (TJs) open due to the disappearance of TJ proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia, thus allowing macrophage migration and forming cerebral aneurysm. Therefore, cerebral aneurysm formation can be prevented by increasing TJs of the artery endothelium. Interestingly, statin, which can reduce saccular aneurysm, may prevent aneurysm formation through acting on different steps, but the underlying mechanism remains unclear. In this study, angiotensin II (Ang II) significantly increased the permeability of human arterial endothelial cell (HAEC). Moreover, the distribution of ZO-1 in cell-cell junction area and the total expression in HAECs were significantly decreased by Ang II treatment. However, the abnormal distribution and decreased expression of ZO-1 and hyperpermeability of HAECs were significantly reversed by pretreatment with atorvastatin. Furthermore, Ang II-induced phosphorylations of MYPT1, LIMK and MLC2 were significantly inhibited with atorvastatin or Rho kinase (ROCK) inhibitor (H1152) pretreatment. Knockdown of ROCK-II probably abolished Ang II-induced abnormal ZO-1 distribution and expression deficiency and hyperpermeability of HAECs. In conclusion, atorvastatin prevented Ang II-induced rupture of HAEC monolayers by suppressing the ROCK signaling pathway. Our results may explain, at least in part, some beneficial effects of statins on cardiovascular diseases such as intracranial aneurysm. Copyright © 2015 Elsevier Inc. All rights reserved.

Evidence for preferential flow through sandstone aquifers in Southern Wisconsin

USGS Publications Warehouse

Swanson, S.K.; Bahr, J.M.; Bradbury, K.R.; Anderson, K.M.

2006-01-01

Sandstones often escape extensive hydrogeologic characterization due to their high primary porosity and perceived homogeneity of permeability. This study provides evidence for laterally extensive, high permeability zones in the Tunnel City Group, an undeformed, Cambrian-aged sandstone unit that exists in the subsurface throughout much of central and southern Wisconsin, USA. Several discrete high-permeability zones were identified in boreholes using flow logging and slug tests, and the interconnectedness of the features was tested using a site-specific numerical model for springs in the region. Explicit incorporation of a high-permeability layer leads to improvements in the flux calibration over simulations that lack the features, thus supporting the hydraulic continuity of high-permeability zones in the sandstone aquifer over tens of kilometers. The results suggest that stratigraphically controlled heterogeneities like contrasts in lithology or bedding-plane fractures, which have been shown to strongly influence the flow of groundwater in more heterogeneous sedimentary rocks, may also deserve close examination in sandstone aquifers. ?? 2005 Elsevier B.V. All rights reserved.

Effects of ultrasound and sodium lauryl sulfate on the transdermal delivery of hydrophilic permeants: Comparative in vitro studies with full-thickness and split-thickness pig and human skin.

PubMed

Seto, Jennifer E; Polat, Baris E; Lopez, Renata F V; Blankschtein, Daniel; Langer, Robert

2010-07-01

The simultaneous application of ultrasound and the surfactant sodium lauryl sulfate (referred to as US/SLS) to skin enhances transdermal drug delivery (TDD) in a synergistic mechanical and chemical manner. Since full-thickness skin (FTS) and split-thickness skin (STS) differ in mechanical strength, US/SLS treatment may have different effects on their transdermal transport pathways. Therefore, we evaluated STS as an alternative to the well-established US/SLS-treated FTS model for TDD studies of hydrophilic permeants. We utilized the aqueous porous pathway model to compare the effects of US/SLS treatment on the skin permeability and the pore radius of pig and human FTS and STS over a range of skin electrical resistivity values. Our findings indicate that the US/SLS-treated pig skin models exhibit similar permeabilities and pore radii, but the human skin models do not. Furthermore, the US/SLS-enhanced delivery of gold nanoparticles and quantum dots (two model hydrophilic macromolecules) is greater through pig STS than through pig FTS, due to the presence of less dermis that acts as an artificial barrier to macromolecules. In spite of greater variability in correlations between STS permeability and resistivity, our findings strongly suggest the use of 700microm-thick pig STS to investigate the in vitro US/SLS-enhanced delivery of hydrophilic macromolecules. 2010 Elsevier B.V. All rights reserved.

Biopharmaceutics permeability classification of lorcaserin, a selective 5-hydroxytryptamine 2C agonist: method suitability and permeability class membership.

PubMed

Chen, Chuan; Ma, Michael G; Fullenwider, Cody L; Chen, Weichao G; Sadeque, Abu J M

2013-12-02

The objectives of the study were (1) to demonstrate that a Caco-2 cell-based permeability assay, developed in our laboratory, is suitable to identify the permeability classification according to the US Food and Drug Administration Biopharmaceutics Classification System guidance, and (2) to use the validated Caco-2 method to determine permeability class membership of lorcaserin. Lorcaserin, marketed in United States as Belviq, is a selective human 5-hydroxytryptamine 2C agonist used for weight management. First, the permeability of twenty commercially available drugs was determined in the apical-to-basolateral direction at a final concentration of 10 μM, with the pH of transporter buffer in the apical and basolateral compartments being 6.8 and 7.4, respectively. A rank-order relationship between in vitro permeability results and the extent of human intestinal absorption for the drugs tested was observed. Second, the apparent permeability coefficient values of lorcaserin at 2, 20, and 200 μM and apical pH values of 6.8 and 7.4 in the apical-to-basolateral direction were determined using the validated method and found to be comparable to those of the high-permeability internal standard metoprolol. Lorcaserin permeability across Caco-2 cell monolayers was not dependent on the variation of apical pH. Furthermore, lorcaserin was not a substrate for efflux transporters such as P-glycoprotein. In conclusion, using the validated Caco-2 permeability assay, it was shown that lorcaserin is a highly permeable compound.

Perm-Fit: a new program to estimate permeability at high P-T conditions

NASA Astrophysics Data System (ADS)

Moulas, Evangelos; Madonna, Claudio

2016-04-01

Several geological processes are controlled by porous fluid flow. The circulation of porous fluids influences many physical phenomena and in turn it depends on the rock permeability. The permeability of rocks is a physical property that needs to be measured since it depends on many factors such as secondary porosity (fractures etc). We present a numerical approach to estimate permeability using the transient step method (Brace et al., 1968). When a non-reacting, compressible fluid is considered in a relative incompressible solid matrix, the only unknown parameter in the equations of porous flow is permeability. Porosity is assumed to be known and the physical properties of the fluid (compressibility, density, viscosity) are taken from the NIST database. Forward numerical calculations for different values of permeability are used and the results are compared to experimental measurements. The extracted permeability value is the one that minimizes the misfit between experimental and numerical results. The uncertainty on the value of permeability is estimated using a Monte Carlo method. REFERENCES Brace, W.F., Walsh J.B., & Frangos, W.T. 1968: Permeability of Granite under High Pressure, Journal of Geophysical Research, 73, 6, 2225-2236

The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)

EPA Science Inventory

The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...

Characterizing SHP2 as a Novel Therapeutic Target in Breast Cancer

DTIC Science & Technology

2013-02-01

attempted to elucidate interactions with molecular docking (5). The peptide was docked into the SH2 active site of 2SHP.pdb (with SH2 domains...activated protein kinase (MAPK) pathway, which is read as a drop in phosphorylated ERK protein(3). 5 First, the problem of cell permeability

Do the recommended standards for in vitro biopharmaceutic classification of drug permeability meet the "passive transport" criterion for biowaivers?

PubMed

Žakelj, Simon; Berginc, Katja; Roškar, Robert; Kraljič, Bor; Kristl, Albin

2013-01-01

BCS based biowaivers are recognized by major regulatory agencies. An application for a biowaiver can be supported by or even based on "in vitro" measurements of drug permeability. However, guidelines limit the application of biowaivers to drug substances that are transported only by passive mechanisms. Regarding published permeability data as well as measurements obtained in our institution, one can rarely observe drug substances that conform to this very strict criterion. Therefore, we measured the apparent permeability coefficients of 13 drugs recommended by FDA's Guidance to be used as standards for "in vitro" permeability classification. The asymmetry of permeability data determined for both directions (mucosal-to-serosal and serosalto- mucosal) through the rat small intestine revealed significant active transport for four out of the nine high-permeability standards and for all four low-permeability standard drugs. As could be expected, this asymmetry was abolished at 4°C on rat intestine. The permeability of all nine high-permeability, but none of the low permeability standards, was also much lower when measured with intestinal tissue, Caco-2 cell monolayers or artificial membranes at 4°C compared to standard conditions (37°C). Additionally, concurrent testing of several standard drugs revealed that membrane transport can be affected by the use of internal permeability standards. The implications of the results are discussed regarding the regulatory aspects of biopharmaceutical classification, good practice in drug permeability evaluation and regarding the general relevance of transport proteins with broad specificity in drug absorption.

Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high fat-fed mice

USDA-ARS?s Scientific Manuscript database

Objective: Microbial dysbiosis and increased intestinal permeability is a target for prevention or reversal of weight gain in high-fat (HF) diet-induced obesity (DIO); however, it is not known whether decreased intestinal permeability is necessary or sufficient for weight loss. Prebiotic milk oligos...

Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species

PubMed Central

Webster, Keith A

2013-01-01

Excess generation of reactive oxygen species (ROS) and cytosolic calcium accumulation play major roles in the initiation of programmed cell death during acute myocardial infarction. Cell death may include necrosis, apoptosis and autophagy, and combinations thereof. During ischemia, calcium handling between the sarcoplasmic reticulum and myofilament is disrupted and calcium is diverted to the mitochondria causing swelling. Reperfusion, while essential for survival, reactivates energy transduction and contractility and causes the release of ROS and additional ionic imbalance. During acute ischemia–reperfusion, the principal death pathways are programmed necrosis and apoptosis through the intrinsic pathway, initiated by the opening of the mitochondrial permeability transition pore and outer mitochondrial membrane permeabilization, respectively. Despite intense investigation, the mechanisms of action and modes of regulation of mitochondrial membrane permeabilization are incompletely understood. Extrinsic apoptosis, necroptosis and autophagy may also contribute to ischemia–reperfusion injury. In this review, the roles of dysregulated calcium and ROS and the contributions of Bcl-2 proteins, as well as mitochondrial morphology in promoting mitochondrial membrane permeability change and the ensuing cell death during myocardial infarction are discussed. PMID:23176689

Plasmodesmata in integrated cell signalling: insights from development and environmental signals and stresses

PubMed Central

Sager, Ross; Lee, Jung-Youn

2014-01-01

To survive as sedentary organisms built of immobile cells, plants require an effective intercellular communication system, both locally between neighbouring cells within each tissue and systemically across distantly located organs. Such a system enables cells to coordinate their intracellular activities and produce concerted responses to internal and external stimuli. Plasmodesmata, membrane-lined intercellular channels, are essential for direct cell-to-cell communication involving exchange of diffusible factors, including signalling and information molecules. Recent advances corroborate that plasmodesmata are not passive but rather highly dynamic channels, in that their density in the cell walls and gating activities are tightly linked to developmental and physiological processes. Moreover, it is becoming clear that specific hormonal signalling pathways play crucial roles in relaying primary cellular signals to plasmodesmata. In this review, we examine a number of studies in which plasmodesmal structure, occurrence, and/or permeability responses are found to be altered upon given cellular or environmental signals, and discuss common themes illustrating how plasmodesmal regulation is integrated into specific cellular signalling pathways. PMID:25262225

Manipulating the mitochondria activity in human hepatic cell line Huh7 by low-power laser irradiation

PubMed Central

Lynnyk, Anna; Lunova, Mariia; Jirsa, Milan; Egorova, Daria; Kulikov, Andrei; Kubinová, Šárka; Lunov, Oleg; Dejneka, Alexandr

2018-01-01

Low-power laser irradiation of red light has been recognized as a promising tool across a vast variety of biomedical applications. However, deep understanding of the molecular mechanisms behind laser-induced cellular effects remains a significant challenge. Here, we investigated mechanisms involved in the death process in human hepatic cell line Huh7 at a laser irradiation. We decoupled distinct cell death pathways targeted by laser irradiations of different powers. Our data demonstrate that high dose laser irradiation exhibited the highest levels of total reactive oxygen species production, leading to cyclophilin D-related necrosis via the mitochondrial permeability transition. On the contrary, low dose laser irradiation resulted in the nuclear accumulation of superoxide and apoptosis execution. Our findings offer a novel insight into laser-induced cellular responses, and reveal distinct cell death pathways triggered by laser irradiation. The observed link between mitochondria depolarization and triggering ROS could be a fundamental phenomenon in laser-induced cellular responses. PMID:29541521

Self-organization of hydrothermal outflow and recharge in young oceanic crust: Constraints from open-top porous convection analog experiments

NASA Astrophysics Data System (ADS)

Mittelstaedt, E. L.; Olive, J. A. L.; Barreyre, T.

2016-12-01

Hydrothermal circulation at the axis of mid-ocean ridges has a profound effect on chemical and biological processes in the deep ocean, and influences the thermo-mechanical state of young oceanic lithosphere. Yet, the geometry of fluid pathways beneath the seafloor and its relation to spatial gradients in crustal permeability remain enigmatic. Here we present new laboratory models of hydrothermal circulation aimed at constraining the self-organization of porous convection cells in homogeneous as well as highly heterogeneous crust analogs. Oceanic crust analogs of known permeability are constructed using uniform glass spheres and 3-D printed plastics with a network of mutually perpendicular tubes. These materials are saturated with corn syrup-water mixtures and heated at their base by a resistive silicone strip heater to initiate thermal convection. A layer of pure fluid (i.e., an analog ocean) overlies the porous medium and allows an "open-top" boundary condition. Areas of fluid discharge from the crust into the ocean are identified by illuminating microscopic glass particles carried by the fluid, using laser sheets. Using particle image velocimetry, we estimate fluid discharge rates as well as the location and extent of fluid recharge. Thermo-couples distributed throughout the crust provide insights into the geometry of convection cells at depth, and enable estimates of convective heat flux, which can be compared to the heat supplied at the base of the system. Preliminary results indicate that in homogeneous crust, convection is largely confined to the narrow slot overlying the heat source. Regularly spaced discharge zones appear focused while recharge areas appear diffuse, and qualitatively resemble the along-axis distribution of hydrothermal fields at oceanic spreading centers. By varying the permeability of the crustal analogs, the viscosity of the convecting fluid, and the imposed basal temperature, our experiments span Rayleigh numbers between 10 and 10,000. This allows us to precisely map the conditions of convection initiation, and test scaling relations between the Nusselt and Rayleigh numbers. Finally, we investigate how these scalings and convection geometry change when a slot of high-permeability material (i.e., an analog fault) is introduced in the middle of the porous domain.

Modeling of leachate generation from MSW landfills by a 2-dimensional 2-domain approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fellner, Johann, E-mail: j.fellner@tuwien.ac.a; Brunner, Paul H., E-mail: paul.h.brunner@tuwien.ac.a

2010-11-15

The flow of water through Municipal Solid Waste (MSW) landfills is highly non-uniform and dominated by preferential pathways. Thus, concepts to simulate landfill behavior require that a heterogeneous flow regime is considered. Recent models are based on a 2-domain approach, differentiating between channel domain with high hydraulic conductivity, and matrix domain of slow water movement with high water retention capacity. These models focus on the mathematical description of rapid water flow in channel domain. The present paper highlights the importance of water exchange between the two domains, and expands the 1-dimensional, 2-domain flow model by taking into account water flowsmore » in two dimensions. A flow field consisting of a vertical path (channel domain) surrounded by the waste mass (matrix domain) is defined using the software HYDRUS-2D. When the new model is calibrated using data sets from a MSW-landfill site the predicted leachate generation corresponds well with the observed leachate discharge. An overall model efficiency in terms of r{sup 2} of 0.76 was determined for a simulation period of almost 4 years. The results confirm that water in landfills follows a preferential path way characterized by high permeability (K{sub s} = 300 m/d) and zero retention capacity, while the bulk of the landfill (matrix domain) is characterized by low permeability (K{sub s} = 0.1 m/d) and high retention capacity. The most sensitive parameters of the model are the hydraulic conductivities of the channel domain and the matrix domain, and the anisotropy of the matrix domain.« less

Analysis of dispersion and attenuation of surface waves in poroelastic media in the exploration-seismic frequency band

USGS Publications Warehouse

Zhang, Y.; Xu, Y.; Xia, J.

2011-01-01

We analyse dispersion and attenuation of surface waves at free surfaces of possible vacuum/poroelastic media: permeable-'open pore', impermeable-'closed pore' and partially permeable boundaries, which have not been previously reported in detail by researchers, under different surface-permeable, viscous-damping, elastic and fluid-flowing conditions. Our discussion is focused on their characteristics in the exploration-seismic frequency band (a few through 200 Hz) for near-surface applications. We find two surface-wave modes exist, R1 waves for all conditions, and R2 waves for closed-pore and partially permeable conditions. For R1 waves, velocities disperse most under partially permeable conditions and least under the open-pore condition. High-coupling damping coefficients move the main dispersion frequency range to high frequencies. There is an f1 frequency dependence as a constant-Q model for attenuation at high frequencies. R1 waves for the open pore are most sensitive to elastic modulus variation, but least sensitive to tortuosities variation. R1 waves for partially permeable surface radiate as non-physical waves (Im(k) < 0) at low frequencies. For R2 waves, velocities are slightly lower than the bulk slow P2 waves. At low frequencies, both velocity and attenuation are diffusive of f1/2 frequency dependence, as P2 waves. It is found that for partially permeable surfaces, the attenuation displays -f1 frequency dependence as frequency increasing. High surface permeability, low-coupling damping coefficients, low Poisson's ratios, and low tortuosities increase the slope of the -f1 dependence. When the attenuation coefficients reach 0, R2 waves for partially permeable surface begin to radiate as non-physical waves. ?? 2011 The Authors Geophysical Journal International ?? 2011 RAS.

Claudins and the Kidney Volume 75: Annual Review of Physiology

PubMed Central

Hou, Jianghui; Rajagopal, Madhumitha; Yu, Alan S. L.

2013-01-01

Claudins are tight junction membrane proteins that regulate paracellular permeability of renal epithelia to small ions, solutes and water. Claudins interact within the cell membrane and between neighboring cells to form tight junction strands and constitute both the paracellular barrier and pore. The first extracellular domain of claudins is thought to be the pore-lining domain and contains the determinants of charge selectivity. Multiple claudins are expressed in different nephron segments and this likely determines the permeability properties of each segment. Recent evidence has identified claudin-2 as constituting the cation-reabsorptive pathway in the proximal tubule, claudin-14, -16 and -19 as forming a complex that regulates calcium transport in the thick ascending limb of the loop of Henle, and claudin-4, -7 and -8 as determinants of collecting duct choride permeability. Mutations in claudin-16 and -19 cause familial hypercalciuric hypomagnesemia. The roles of other claudins in kidney diseases remain to be fully elucidated. PMID:23140368

Monetizing Leakage Risk of Geologic CO2 Storage using Wellbore Permeability Frequency Distributions

NASA Astrophysics Data System (ADS)

Bielicki, Jeffrey; Fitts, Jeffrey; Peters, Catherine; Wilson, Elizabeth

2013-04-01

Carbon dioxide (CO2) may be captured from large point sources (e.g., coal-fired power plants, oil refineries, cement manufacturers) and injected into deep sedimentary basins for storage, or sequestration, from the atmosphere. This technology—CO2 Capture and Storage (CCS)—may be a significant component of the portfolio of technologies deployed to mitigate climate change. But injected CO2, or the brine it displaces, may leak from the storage reservoir through a variety of natural and manmade pathways, including existing wells and wellbores. Such leakage will incur costs to a variety of stakeholders, which may affect the desirability of potential CO2 injection locations as well as the feasibility of the CCS approach writ large. Consequently, analyzing and monetizing leakage risk is necessary to develop CCS as a viable technological option to mitigate climate change. Risk is the product of the probability of an outcome and the impact of that outcome. Assessment of leakage risk from geologic CO2 storage reservoirs requires an analysis of the probabilities and magnitudes of leakage, identification of the outcomes that may result from leakage, and an assessment of the expected economic costs of those outcomes. One critical uncertainty regarding the rate and magnitude of leakage is determined by the leakiness of the well leakage pathway. This leakiness is characterized by a leakage permeability for the pathway, and recent work has sought to determine frequency distributions for the leakage permeabilities of wells and wellbores. We conduct a probabilistic analysis of leakage and monetized leakage risk for CO2 injection locations in the Michigan Sedimentary Basin (USA) using empirically derived frequency distributions for wellbore leakage permeabilities. To conduct this probabilistic risk analysis, we apply the RISCS (Risk Interference of Subsurface CO2 Storage) model (Bielicki et al, 2013a, 2012b) to injection into the Mt. Simon Sandstone. RISCS monetizes leakage risk by combining 3D geospatial data with fluid-flow simulations from the ELSA (Estimating Leakage Semi-Analytically) model (e.g., Celia and Nordbotten, 2006) and the Leakage Impact Valuation (LIV) method (Pollak et al, 2013; Bielicki et al, 2013). We extend RISCS to iterate ELSA semi-analytic modeling simulations by drawing values from the frequency distribution of leakage permeabilities. The iterations assign these values to existing wells in the basin, and the probabilistic risk analysis thus incorporates the uncertainty of the extent of leakage. We show that monetized leakage risk can vary significantly over tens of kilometers, and we identify "hot spots" favorable to CO2 injection based on the monetized leakage risk for each potential location in the basin.

Simulating the Heterogeneity in Braided Channel Belt Deposits: 2. Examples of Results and Comparison to Natural Deposits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guin, Arijit; Ramanathan, Ramya; Ritzi, Robert W.

In Part 1 of this series we presented a methodology and a code for modeling the hierarchical sedimentary architecture in braided channel belt deposits. Here, in Part 2, the code was used to create a digital model of this architecture, and the corresponding spatial distribution of permeability. The simulated architecture was compared to the real stratal architecture observed in an abandoned channel belt of the Sagavanirktok River, Alaska by Lunt et al. (2004). The comparisons included assessments of similarity which were both qualitative and quantitative. From the qualitative comparisons we conclude that a synthetic deposit created by the code hasmore » unit types, at each level, with a geometry which is generally consistent with the geometry of unit types observed in the field. The digital unit types would generally be recognized as representing their counterparts in nature, including cross stratasets, lobate and scroll bar deposits, channel fills, etc. Furthermore, the synthetic deposit has a hierarchical spatial relationship among these units which represents how the unit types are observed in field exposures and in geophysical images. In quantitative comparisons the proportions and the length, width, and height of unit types at different scales, across all levels of the stratal hierarchy compare well between the digital and the natural deposits. A number of important attributes of the channel belt model were shown to be influenced by more than one level within the hierarchy of stratal architecture. First, the high-permeability open-framework gravels percolated at all levels and thus formed preferential flow pathways. Open framework gravels are indeed known to form preferential flow pathways in natural channel belt deposits. The nature of a percolating cluster changed across different levels of the hierarchy of stratal architecture. As a result of this geologic structure, the percolation occurs at proportions of open-framework gravels below the theoretical percolation threshold for random infinite media. Second, when the channel belt model was populated with permeability distributions by lowest-level unit type, the composite permeability semivariogram contained structures that were identifiable at more than one scale, and each of these structures could be directly linked to unit types of different scales existing at different levels within the hierarchy of strata. These collective results are encouraging with respect to our goal that this model be relevant as a base case in future studies for testing ideas in research addressing the upscaling problem in aquifers and reservoirs with multi-scale heterogeneity.« less

Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alves, Vinicius M.; Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599; Muratov, Eugene

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, wemore » found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R{sup 2} = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q{sup 2}{sub ext} = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin sensitization and skin permeability has been found. • Structural rules for optimizing sensitization and penetration were established.« less

Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells.

PubMed

Shao, Yuxin; Wolf, Patricia G; Guo, Shuangshuang; Guo, Yuming; Gaskins, H Rex; Zhang, Bingkun

2017-05-01

Zinc plays an important role in maintaining intestinal barrier function as well as modulating cellular signaling recognition and protein kinase activities. The phosphatidylinositol 3-kinase (PI3K) cascade has been demonstrated to affect intercellular integrity and tight junction (TJ) proteins. The current study investigated the hypothesis that zinc regulates intestinal intercellular junction integrity through the PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. A transwell model of Caco-2 cell was incubated with 0, 50 and 100 μM of zinc at various time points. Transepithelial electrical resistance (TEER), paracellular permeability, TJ proteins, cell proliferation, differentiation and cell damage were measured. Compared with controls, 50 and 100 μM of zinc increased cell growth at 6, 12 and 24 h and the expression of proliferating cell nuclear antigen at 24 h. Zinc (100 μM) significantly elevated TEER at 6-24 h and reduced TJ permeability at 24 h, accompanied by the up-regulation of alkaline phosphatase (AP) activity and zonula occludens (ZO)-1 expression. In addition, zinc (100 μM) affected the PI3K/AKT/mTOR pathway by stimulating phosphorylation of AKT and the downstream target mTOR. Inhibition of PI3K signaling by LY294002 counteracted zinc promotion, as shown by a decrease in AP activity, TEER, the abundance of ZO-1 and phosphorylation of AKT and mTOR. Additionally, TJ permeability and the expression of caspase-3 and LC3II (markers of cell damage) were increased by addition of PI3K inhibitor. In conclusion, the activation of PI3K/AKT/mTOR signaling by zinc is involved in improving intestinal barrier function by enhancing cell differentiation and expression of TJ protein ZO-1. Copyright © 2017 Elsevier Inc. All rights reserved.

Induction of a non-specific permeability transition in mitochondria from Yarrowia lipolytica and Dipodascus (Endomyces) magnusii yeasts.

PubMed

Kovaleva, Mariya V; Sukhanova, Evgeniya I; Trendeleva, Tatyana A; Zyl'kova, Marina V; Ural'skaya, Ludmila A; Popova, Kristina M; Saris, Nils-Erik L; Zvyagilskaya, Renata A

2009-06-01

In this study we used tightly-coupled mitochondria from Yarrowia lipolytica and Dipodascus (Endomyces) magnusii yeasts, possessing a respiratory chain with the usual three points of energy conservation. High-amplitude swelling and collapse of the membrane potential were used as parameters for demonstrating induction of the mitochondrial permeability transition due to opening of a pore (mPTP). Mitochondria from Y. lipolytica, lacking a natural mitochondrial Ca(2+) uptake pathway, and from D. magnusii, harboring a high-capacitive, regulated mitochondrial Ca(2+) transport system (Bazhenova et al. J Biol Chem 273:4372-4377, 1998a; Bazhenova et al. Biochim Biophys Acta 1371:96-100, 1998b; Deryabina and Zvyagilskaya Biochemistry (Moscow) 65:1352-1356, 2000; Deryabina et al. J Biol Chem 276:47801-47806, 2001) were very resistant to Ca(2+) overload. However, exposure of yeast mitochondria to 50-100 microM Ca(2+) in the presence of the Ca(2+) ionophore ETH129 induced collapse of the membrane potential, possibly due to activation of the fatty acid-dependent Ca(2+)/nH(+)-antiporter, with no classical mPTP induction. The absence of response in yeast mitochondria was not simply due to structural limitations, since large-amplitude swelling occurred in the presence of alamethicin, a hydrophobic, helical peptide, forming voltage-sensitive ion channels in lipid membranes. Ca(2+)- ETH129-induced activation of the Ca(2+)/H(+)-antiport system was inhibited and prevented by bovine serum albumin, and partially by inorganic phosphate and ATP. We subjected yeast mitochondria to other conditions known to induce the permeability transition in animal mitochondria, i.e., Ca(2+) overload (in the presence of ETH129) combined with palmitic acid (Mironova et al. J Bioenerg Biomembr 33:319-331, 2001; Sultan and Sokolove Arch Biochem Biophys 386:37-51, 2001), SH-reagents, carboxyatractyloside (an inhibitor of the ADP/ATP translocator), depletion of intramitochondrial adenine nucleotide pools, deenergization of mitochondria, and shifting to acidic pH values in the presence of high phosphate concentrations. None of the above-mentioned substances or conditions induced a mPTP-like pore. It is thus evident that the permeability transition in yeast mitochondria is not coupled with Ca(2+) uptake and is differently regulated compared to the mPTP of animal mitochondria.

Numerical Modeling of Hydrothermal Circulation at the Longqi-1 Field: Southwest Indian Ridge

NASA Astrophysics Data System (ADS)

Guo, Z.; Lowell, R. P.; Tao, C.; Rupke, L.; Lewis, K. C.

2017-12-01

The Longqi-1(Dragon Flag) hydrothermal field is the first high-temperature hydrothermal system observed on the ultra-slow spreading Southwest Indian Ridge. Hydrothermal vents with temperatures near 380 °C are localized by detachment faulting within which extensional deformation likely increases permeability to provide preferred pathways for hydrothermal discharge. To better understand the Longqi-1 circulation system, we construct a 2-D numerical simulations in a NaCl- H2O fluid constrained by key observational data, such as vent temperature and heat output, crust structure derived from seismic data, and fault zone geometry deduced from seismicity. Heat output from AUV surveys is estimated to be » 300 ± 100 MW, and this value, in conjunction with vent temperature was used with the single-pass modeling approach to obtain an average permeability of 10-13 m-2 within the fault zone. In analogy with other fault-controlled hydrothermal systems such as Logatchev-1 we assume a lower background permeability of 10-14 m-2. The top boundary of the system is permeable and maintained at constant seafloor pressure, which is divided into two parts by the detachment fault. The pressure of the southern part is lower than the northern part to simulate the effect of the seafloor topography. The top boundary is upstream weighted to allow high temperature fluid to exit, while recharging fluid is maintained at 10°C. The bottom boundary is impermeable and is given a fixed temperature distribution at a depth of 7 km below the seafloor. The highest value Tmax is maintained over a distance given lateral distance and decreases linearly towards two ends to 300 °C. The salinity is set to 3.2 wt. % NaCl, and the simulations are assumed to be single phase. The results show that with a 7 km deep circulation system, Tmax = 550 oC gives a reasonable temperature and heat output of venting plume.We infer that the observed high salinity results from serpentinization reactions. Assuming all salinity in excess of seawater comes from uptake of H2O during serpentinization, we can estimate the rate of reaction and heat release of serpentinezation based on a simplified reaction equation, observed heat output and salinity data. The estimated rate of heat release during serpentinization is 20 MW. This is approximately 10% of the heat output of Dragon Flag vent field.

Amorphous Silk Fibroin Membranes for Separation of CO2

NASA Technical Reports Server (NTRS)

Aberg, Christopher M.; Patel, Anand K.; Gil, Eun Seok; Spontak, Richard J.; Hagg, May-Britt

2009-01-01

Amorphous silk fibroin has shown promise as a polymeric material derivable from natural sources for making membranes for use in removing CO2 from mixed-gas streams. For most applications of silk fibroin, for purposes other than gas separation, this material is used in its highly crystalline, nearly natural form because this form has uncommonly high tensile strength. However, the crystalline phase of silk fibroin is impermeable, making it necessary to convert the material to amorphous form to obtain the high permeability needed for gas separation. Accordingly, one aspect of the present development is a process for generating amorphous silk fibroin by treating native silk fibroin in an aqueous methanol/salt solution. The resulting material remains self-standing and can be prepared as thin film suitable for permeation testing. The permeability of this material by pure CO2 has been found to be highly improved, and its mixed-gas permeability has been found to exceed the mixed-gas permeabilities of several ultrahigh-CO2-permeable synthetic polymers. Only one of the synthetic polymers poly(trimethylsilylpropyne) [PTMSP] may be more highly permeable by CO2. PTMSP becomes unstable with time, whereas amorphous silk should not, although at the time of this reporting this has not been conclusively proven.

Fine-scale in situ measurement of riverbed nitrate production and consumption in an armored permeable riverbed.

PubMed

Lansdown, Katrina; Heppell, Catherine M; Dossena, Matteo; Ullah, Sami; Heathwaite, A Louise; Binley, Andrew; Zhang, Hao; Trimmer, Mark

2014-04-15

Alteration of the global nitrogen cycle by man has increased nitrogen loading in waterways considerably, often with harmful consequences for aquatic ecosystems. Dynamic redox conditions within riverbeds support a variety of nitrogen transformations, some of which can attenuate this burden. In reality, however, assessing the importance of processes besides perhaps denitrification is difficult, due to a sparseness of data, especially in situ, where sediment structure and hydrologic pathways are intact. Here we show in situ within a permeable riverbed, through injections of (15)N-labeled substrates, that nitrate can be either consumed through denitrification or produced through nitrification, at a previously unresolved fine (centimeter) scale. Nitrification and denitrification occupy different niches in the riverbed, with denitrification occurring across a broad chemical gradient while nitrification is restricted to more oxic sediments. The narrow niche width for nitrification is in effect a break point, with the switch from activity "on" to activity "off" regulated by interactions between subsurface chemistry and hydrology. Although maxima for denitrification and nitrification occur at opposing ends of a chemical gradient, high potentials for both nitrate production and consumption can overlap when groundwater upwelling is strong.

Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

PubMed Central

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R2=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q2ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. PMID:25560673

Graphene oxide membranes with high permeability and selectivity for dehumidification of air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, Yongsoon; Liu, Wei; Schwenzer, Birgit

Hierarchically stacked 2D graphene oxide (GO) membranes are a fascinating and promising new class of materials with the potential for radically improved water vapor/gas separation with excellent selectivity and high permeability. This paper details dehumidification results from flowing gas mixtures through free-standing GO membrane samples prepared by a casting method. The first demonstrated use of free-standing GO membranes for water vapor separation reveals outstanding water vapor permeability and H2O/N2 selectivity. Free-standing GO membranes exhibit extremely high water vapor permeability of 1.82 x 105 Barrer and a water vapor permeance of 1.01 x 10-5 mol/m2sPa, while the nitrogen permeability was belowmore » the system’s detection limit, yielding a selectivity >104 in 80% relative humidity (RH) air at 30.8 °C. The results show great potential for a range of energy conversion and environmental applications« less

Alternative complement pathway activation increases mortality in a model of burn injury in mice.

PubMed Central

Gelfand, J A; Donelan, M; Hawiger, A; Burke, J F

1982-01-01

We have studied the role of the complement system in burn injury in an experimental model in mice. A 25% body surface area, full-thickness scald wound was produced in anesthetized animals. Massive activation of the alternative complement pathway, but not the classical pathway, was seen. This activation was associated with the generation of neutrophil aggregating activity in the plasma, neutrophil aggregates in the lungs, increased pulmonary vascular permeability, and increased lung edema formation. Decomplementation with cobra venom factor (CVF) or genetic C5 deficiency diminished these pathologic changes, and CVF pretreatment substantially reduced burn mortality in the first 24 h. Preliminary data show that human burn patients have a similar pattern of complement activation involving predominantly the alternative pathway, indicating the possible relevance of the murine model to human disease. Images PMID:7174787

Regulation of tight junction permeability with switch-like speed.

PubMed

Beyenbach, Klaus W

2003-09-01

The case is made that tight junctions can undergo large reversible conductance changes in a matter of seconds and yet preserve their permselectivity. The diuretic peptide leucokinin transforms (renal) Malpighian tubules of the yellow fever mosquito from a moderately tight epithelium to a leaky epithelium by increasing the chloride-conductance of the paracellular shunt pathway. The nine-fold increase in the paracellular chloride-conductance brings about a non-selective stimulation of transepithelial sodium chloride and potassium chloride secretion, as expected from a conductance increase in the pathway taken by the counterion of sodium and potassium. The leucokinin signaling pathway consists in part of a receptor coupled G-protein, phospholipase C, inositol-1,4,5-trisphosphate, and increased intracellular calcium concentration that bring about the increase in the paracellular, tight junction chloride-conductance. As the conductance of the tight junction pathway increases it becomes more selective for the transepithelial passage of chloride. Epithelial cells in Malpighian tubules taper to tight junctions at their lateral edges exposing them directly to apical and serosal solutions. Furthermore, evolutionary pressures to excrete salt and water at high rates without the aid of glomerular filtration have led to powerful mechanisms of tubular secretion, capable of diuresis when the mosquito is challenged with the volume expansion of a blood meal. The tubular diuresis is mediated in part by increasing the paracellular chloride conductance. Thus, anatomical and physiological specializations in Malpighian tubules combine to yield the evidence for the dynamic hormonal regulation of the tight junction pathway.

Reactive transport simulations of alternative flow pathways in the ambient unsaturated zone at Yucca Mountain, Nevada

NASA Astrophysics Data System (ADS)

Browning, L.; Murphy, W.; Manepally, C.; Fedors, R.

2003-04-01

Uncertainties in simulated ambient system unsaturated zone flow could have a significant impact on performance evaluations of the proposed nuclear waste repository at Yucca Mountain, Nevada. In addition to determining variations in the quantity of water available to corrode engineered materials and transport radionuclides, model assumptions regarding flow pathways may significantly affect estimates of groundwater chemistry. The manner and extent to which groundwater compositions evolve along a flow pathway are determined mainly by thermohydrologic conditions, the types of reactive materials encountered, and the interaction times with those materials. Simulated groundwater compositions can thus vary significantly depending on whether or not the flow model includes lateral diversion of infiltrating waters, or preferential flow pathways in variably-saturated materials. To assist a regulatory review of a potential license application for a geologic repository for high-level waste, we developed a reactive transport model for the ambient hydrogeochemical system at Yucca Mountain. The model simulates two phase, nonisothermal, advective and diffusive flow and transport through a one dimensional, matrix and fracture continua (dual permeability) containing ten kinetically reactive hydrostatigraphic layers in the vicinity of the SD-9 borehole at Yucca Mountain. In this presentation, we describe how the model was used to evaluate alternative ambient unsaturated zone flow pathways proposed by the U.S. Department of Energy. This abstract is an independent product of the CNWRA and does not necessarily reflect the views or regulatory position of the NRC.

[Effect of multicomponent environment on intestinal permeability of puerarin in biopharmaceutics classification system of Chinese materia medica].

PubMed

Liu, Yang; Wang, Gang; Dong, Ling; Tang, Ming-Min; Zhu, Mei-Ling; Dong, Hong-Huant; Hou, Cheng-Bo

2014-12-01

The evaluation of permeability in biopharmaceutics classification system of Chinese materia medica (CMMBCS) requires multicomponent as a whole in order to conduct research, even in the study of a specific component, should also be put in the multicomponent environment. Based on this principle, the high content components in Gegen Qinlian decoction were used as multicomponent environmental impact factors in the experiment, and the relevant parameters of intestinal permeability about puerarin were measured with using in situ single-pass intestinal perfusion model, to investigate and evaluate the intestinal permeability of puerarin with other high content components. The experimental results showed that different proportions of baicalin, glycyrrhizic acid and berberine had certain influence on intestinal permeability of puerarin, and glycyrrhizic acid could significantly inhibit the intestinal absorption of puerarin, moreover, high concentration of berberine could promote the absorption of puerarin. The research results indicated that the important research ideas of permeability evaluation in biopharmaceutics classification system of Chinese materia medica with fully considering the effects of other ingredients in multicomponent environment.

Estimating the gas hydrate recovery prospects in the western Black Sea basin based on the 3D multiphase flow of fluid and gas components within highly permeable paleo-channel-levee systems

NASA Astrophysics Data System (ADS)

Burwicz, Ewa; Zander, Timo; Rottke, Wolf; Bialas, Joerg; Hensen, Christian; Atgin, Orhan; Haeckel, Matthias

2017-04-01

Gas hydrate deposits are abundant in the Black Sea region and confirmed by direct observations as well as geophysical evidence, such as continuous bottom simulating reflectors (BSRs). Although those gas hydrate accumulations have been well-studied for almost two decades, the migration pathways of methane that charge the gas hydrate stability zone (GHSZ) in the region are unknown. The aim of this study is to explore the most probable gas migration scenarios within a three-dimensional finite element grid based on seismic surveys and available basin cross-sections. We have used the commercial software PetroMod(TM) (Schlumberger) to perform a set of sensitivity studies that narrow the gap between the wide range of sediment properties affecting the multi-phase flow in porous media. The high-resolution model domain focuses on the Danube deep-sea fan and associated buried sandy channel-levee systems whereas the total extension of the model domain covers a larger area of the western Black Sea basin. Such a large model domain allows for investigating biogenic as well as thermogenic methane generation and a permeability driven migration of the free phase of methane on a basin scale to confirm the hypothesis of efficient methane migration into the gas hydrate reservoir layers by horizontal flow along the carrier beds.

Biomass properties and permeability in an immersed hollow fibre membrane bioreactor at high sludge concentrations.

PubMed

Wang, Z Z; Zsirai, T; Connery, K; Fabiyi, M; Larrea, A; Li, J; Judd, S J

2014-01-01

This study aimed to investigate the influence of biomass properties and high mixed liquor suspended solids (MLSS) concentrations on membrane permeability in a pilot-scale hollow fibre membrane bioreactor treating domestic wastewater. Auxiliary molasses solution was added to maintain system operation at constant food-to-microorganisms ratio (F/M = 0.13). Various physicochemical and biological biomass parameters were measured throughout the trial, comprising pre-thickening, thickening and post-thickening periods with reference to the sludge concentration and with aerobic biotreatment continuing throughout. Correlations between dynamic changes in biomass characteristics and membrane permeability decline as well as permeability recovery were further assessed by statistical analyses. Results showed the MLSS concentration to exert the greatest influence on sustainable membrane permeability, with a weaker correlation with particle size distribution. The strong dependence of absolute recovered permeability on wet accumulated solids (WACS) concentration, or clogging propensity, revealed clogging to deleteriously affect membrane permeability decline and recovery (from mechanical declogging and chemical cleaning), with WACS levels increasing with increasing MLSS. Evidence from the study indicated clogging may permanently reduce membrane permeability post declogging and chemical cleaning, corroborating previously reported findings.

Water permeability of acinar cell membranes in the isolated perfused rabbit mandibular salivary gland.

PubMed Central

Steward, M C; Seo, Y; Rawlings, J M; Case, R M

1990-01-01

1. The diffusive water permeability of epithelial cell membranes in the perfused rabbit mandibular salivary gland was measured at 37 degrees C by a 1H nuclear magnetic resonance relaxation method using an extracellular relaxation reagent, gadolinium diethylenetriaminepentaacetic acid (Gd(DTPA)). 2. In glands perfused with a HEPES-buffered solution containing 10 mmol l-1 Gd(DTPA), the spin-lattice (T1) relaxation of the water protons showed two exponential components. The water compartment responsible for the slower component corresponded in magnitude to 71 +/- 5% of the wet weight of the gland, and was attributed to the exchangeable intracellular water of the acinar cells. 3. The rate constant for water efflux from the cells was estimated to be 4.1 +/- 0.1 s-1 which would be consistent with a diffusive membrane permeability (Pd) of approximately 3 x 10(-3) cm s-1. Stimulation with acetylcholine (10(-6) mol l-1) did not cause any detectable change in membrane water permeability. 4. Since the basolateral membrane probably provides the main pathway for water efflux, the osmotic water permeability of this barrier (expressed per gland) was estimated to be less than 6.2 cm3 s-1. This would be insufficient to account for the generation of a near-isosmotic fluid at the flow rates observed during secretion, and suggests that a substantial fraction of the flow of water occurs via a paracellular route. PMID:1966053

Transformable ferroelectric control of dynamic magnetic permeability

NASA Astrophysics Data System (ADS)

Jiang, Changjun; Jia, Chenglong; Wang, Fenglong; Zhou, Cai; Xue, Desheng

2018-02-01

Magnetic permeability, which measures the response of a material to an applied magnetic field, is crucial to the performance of magnetic devices and related technologies. Its dynamic value is usually a complex number with real and imaginary parts that describe, respectively, how much magnetic power can be stored and lost in the material. Control of permeability is therefore closely related to energy redistribution within a magnetic system or energy exchange between magnetic and other degrees of freedom via certain spin-dependent interactions. To avoid a high power consumption, direct manipulation of the permeability with an electric field through magnetoelectric coupling leads to high efficiency and simple operation, but remains a big challenge in both the fundamental physics and material science. Here we report unambiguous evidence of ferroelectric control of dynamic magnetic permeability in a Co /Pb (Mg1/3Nb2/3) 0.7Ti0.3O3 (Co/PMN-PT) heterostructure, in which the ferroelectric PMN-PT acts as an energy source for the ferromagnetic Co film via an interfacial linear magnetoelectric interaction. The electric field tuning of the magnitude and line shape of the permeability offers a highly localized means of controlling magnetization with ultralow power consumption. Additionally, the emergence of negative permeability promises a new way of realizing functional nanoscale metamaterials with adjustable refraction index.

Are the Columbia River Basalts, Columbia Plateau, Idaho, Oregon, and Washington, USA, a viable geothermal target? A preliminary analysis

USGS Publications Warehouse

Burns, Erick R.; Williams, Colin F.; Tolan, Terry; Kaven, Joern Ole

2016-01-01

The successful development of a geothermal electric power generation facility relies on (1) the identification of sufficiently high temperatures at an economically viable depth and (2) the existence of or potential to create and maintain a permeable zone (permeability >10-14 m2) of sufficient size to allow efficient long-term extraction of heat from the reservoir host rock. If both occur at depth under the Columbia Plateau, development of geothermal resources there has the potential to expand both the magnitude and spatial extent of geothermal energy production. However, a number of scientific and technical issues must be resolved in order to evaluate the likelihood that the Columbia River Basalts, or deeper geologic units under the Columbia Plateau, are viable geothermal targets.Recent research has demonstrated that heat flow beneath the Columbia Plateau Regional Aquifer System may be higher than previously measured in relatively shallow (<600 m depth) wells, indicating that sufficient temperatures for electricity generation occur at depths 5 km. The remaining consideration is evaluating the likelihood that naturally high permeability exists, or that it is possible to replicate the high average permeability (approximately 10-14 to 10-12 m2) characteristic of natural hydrothermal reservoirs. From a hydraulic perspective, Columbia River Basalts are typically divided into dense, impermeable flow interiors and interflow zones comprising the top of one flow, the bottom of the overlying flow, and any sedimentary interbed. Interflow zones are highly variable in texture but, at depths <600 m, some of them form highly permeable regional aquifers with connectivity over many tens of kilometers. Below depths of ~600 m, permeability reduction occurs in many interflow zones, caused by the formation of low-temperature hydrothermal alteration minerals (corresponding to temperatures above ~35 °C). However, some high permeability (>10-14 m2) interflows are documented at depths up to ~1,400 m. If the elevated permeability in these zones persists to greater depths, they may provide natural permeability of sufficient magnitude to allow their exploitation as conventional geothermal reservoirs. Alternatively, if the permeability in these interflow zones is less than 10-14 m2 at depth, it may be possible to use hydraulic and thermal stimulation to enhance the permeability of both the interflow zones and the natural jointing within the low-permeability interior portions of individual basalt flows in order to develop Enhanced/Engineered Geothermal System (EGS) reservoirs. The key challenge for an improved Columbia Plateau geothermal assessment is acquiring and interpreting comprehensive field data that can provide quantitative constraints on the recovery of heat from the Columbia River Basalts at depths greater than those currently tested by deep boreholes.

Voltage-dependent calcium-permeable channels in the plasma membrane of a higher plant cell.

PubMed

Thuleau, P; Ward, J M; Ranjeva, R; Schroeder, J I

1994-07-01

Numerous biological assays and pharmacological studies on various higher plant tissues have led to the suggestion that voltage-dependent plasma membrane Ca2+ channels play prominent roles in initiating signal transduction processes during plant growth and development. However, to date no direct evidence has been obtained for the existence of such depolarization-activated Ca2+ channels in the plasma membrane of higher plant cells. Carrot suspension cells (Daucus carota L.) provide a well-suited system to determine whether voltage-dependent Ca2+ channels are present in the plasma membrane of higher plants and to characterize the properties of putative Ca2+ channels. It is known that both depolarization, caused by raising extracellular K+, and exposure to fungal toxins or oligogalacturonides induce Ca2+ influx into carrot cells. By direct application of patch-clamp techniques to isolated carrot protoplasts, we show here that depolarization of the plasma membrane positive to -135 mV activates Ca(2+)-permeable channels. These voltage-dependent ion channels were more permeable to Ca2+ than K+, while displaying large permeabilities to Ba2+ and Mg2+ ions. Ca(2+)-permeable channels showed slow and reversible inactivation. The single-channel conductance was 13 pS in 40 mM CaCl2. These data provide direct evidence for the existence of voltage-dependent Ca2+ channels in the plasma membrane of a higher plant cell and point to physiological mechanisms for plant Ca2+ channel regulation. The depolarization-activated Ca(2+)-permeable channels identified here could constitute a regulated pathway for Ca2+ influx in response to physiologically occurring stimulus-induced depolarizations in higher plant cells.

Hypothesis: Hemolytic Transfusion Reactions Represent an Alternative Type of Anaphylaxis

PubMed Central

Hod, Eldad A.; Sokol, Set A.; Zimring, James C.; Spitalnik, Steven L.

2009-01-01

Classical anaphylaxis is the most severe, and potentially fatal, type of allergic reaction, manifested by hypotension, bronchoconstriction, and vascular permeability. Similarly, a hemolytic transfusion reaction (HTR) is the most feared consequence of blood transfusion. Evidence for the existence of an alternative, IgG-mediated pathway of anaphylaxis may be relevant for explaining the pathophysiology of IgG-mediated-HTRs. The purpose of this review is to summarize the evidence for this alternative pathway of anaphylaxis and to present the hypothesis that an IgG-mediated HTR is one example of this type of anaphylaxis. PMID:18830382

Low power loss and field-insensitive permeability of Fe-6.5%Si powder cores with manganese oxide-coated particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Junnan, E-mail: junnanli1991@163.com, E-mail: rzhgong@hust.edu.cn; Wang, Xian; Xu, Xiaojun

Fe-6.5%Si alloy powders coated with manganese oxides using an innovative in situ process were investigated. The in-situ coating of the insulating oxides was realized with a KMnO{sub 4} solution by a chemical process. The insulating manganese oxides with mixed valance state were verified by X-ray photoelectron spectroscopy analysis. The thickness of the insulating layer on alloy particles was determined to be in a range of 20–210 nm, depending upon the KMnO{sub 4} concentration. The powder core loss and the change in permeability under a DC-bias field were measured at frequencies ranging from 50 to 100 kHz. The experiments indicated that themore » Fe-6.5%Si powder cores with a 210 nm-thick manganese oxide layer not only showed a low core loss of 459 mW/cm{sup 3} at 100 kHz but also showed a small reduction in permeability (μ(H)/μ(0) = 85% for μ = 42) at a DC-bias field of 80 Oe. This work has defined a novel pathway to realizing low core loss and field-insensitive permeability for Fe-Si powder cores.« less

Can a fractured caprock self-heal?

NASA Astrophysics Data System (ADS)

Elkhoury, Jean E.; Detwiler, Russell L.; Ameli, Pasha

2015-05-01

The ability of geologic seals to prevent leakage of fluids injected into the deep subsurface is critical for mitigating risks associated with greenhouse-gas sequestration and natural-gas production. Fractures caused by tectonic or injection-induced stresses create potential leakage pathways that may be further enhanced by mineral dissolution. We present results from reactive-flow experiments in fractured caprock (dolomitic anhydrite), where additional dissolution occurs in the rock matrix adjacent to the fracture surfaces. Preferential dissolution of anhydrite left a compacted layer of dolomite in the fractures. At lower flow rate, rock-fluid reactions proceeded to near equilibrium within the fracture with preferential flow paths persisting over the 6-month duration of the experiment and a negligible change in permeability. At higher flow rate, permeability decreased by a dramatic two orders of magnitude. This laboratory-scale observation of self-healing argues against the likelihood of runaway permeability growth in fractured porous caprock composed of minerals with different solubilities and reaction kinetics. However, scaling arguments suggest that at larger length scales this self-healing process may be offset by the formation of dissolution channels. Our results have relevance beyond the greenhouse-gas sequestration problem. Chemical disequilibrium at waste injection sites and in hydrothermal reservoirs will lead to reactive flows that may also significantly alter formation permeability.

The Relationship Between the Permeability and the Performance of Carrier-Based Dry Powder Inhalation Mixtures: New Insights and Practical Guidance.

PubMed

Shalash, Ahmed O; Khalafallah, Nawal M; Molokhia, Abdulla M; Elsayed, Mustafa M A

2018-02-01

The permeability of a powder bed reflects its particle size distribution, shape, packing, porosity, cohesivity, and tensile strength in a manner relevant to powder fluidization. The relationship between the permeability and the performance of carrier-based dry powder inhalation (DPI) mixtures has, however, aroused controversy. The current study sought to gain new insights into the relationship and to explore its potential applications. We studied eight lactose materials as DPI carriers. The carriers covered a broad permeability range of 0.42-13.53 D and moreover differed in particle size distribution, particle shape, crystal form, and/or porosity. We evaluated the performance of inhalation mixtures of each of these carriers and fluticasone propionate after aerosolization from an Aerolizer®, a model turbulent-shear inhaler, at a flow rate of 60 L/min. Starting from the high permeability side, the inhalation mixture performance increased as the carrier permeability decreased until optimum performance was reached at permeability of ~ 3.2 D. Increased resistance to air flow strengthens aerodynamic dispersion forces. The inhalation mixture performance then decreased as the carrier permeability further decreased. Very high resistance to air flow restricts powder dispersion. The permeability accounted for effects of carrier size, shape, and macroporosity on the performance. We confirmed the relationship by analysis of two literature permeability-performance datasets, representing measurements that differ from ours in terms of carrier grades, drug, technique used to determine permeability, turbulent-shear inhaler, and/or aerosolization flow rate. Permeability provides useful information that can aid development of DPI mixtures for turbulent-shear inhalers. A practical guidance is provided.

Initial results from the Nankai Trough shallow splay and frontal thrust (IODP Expedition 316): Implications for fluid flow

NASA Astrophysics Data System (ADS)

Screaton, E.; Kimura, G.; Curewitz, D.; Scientists, E.

2008-12-01

Integrated Ocean Drilling Program (IODP) Expedition 316 examined the frontal thrust and the shallow portion of the megasplay fault offshore of the Kii peninsula, and was the third drilling expedition of the Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE). NanTroSEIZE will integrate seafloor observations, drilling, and observatories to investigate the processes controlling slip along subduction zone plate boundary fault systems. Site C0004 examined a shallow portion of the splay fault system where it overrides slope basin sediments. Site C0008, located in the slope basin 1 km seaward of Site C0004, provided a reference site for the footwall sediments. Results of drilling indicate that the footwall sediments have dewatered significantly, suggesting permeable routes for fluid escape. These high-permeability pathways might be provided by coarse-grained layers within the slope sediments. In situ dewatering and multiple fluid escape paths will tend to obscure any geochemical signature of flow from depth. Sites C0006 and C0007 examined the frontal thrust system. Although poorly recovered, coarse-grained trench sediments were sampled within the footwall. These permeable sediments would be expected to allow rapid escape of any fluid pressures due to loading. At both sites, low porosities are observed at shallow depths, suggesting removal of overlying material. This observation is consistent with interpretations that the prism is unstable and currently in a period of collapse. Anomalously low temperatures were measured within boreholes at these sites. One possible explanation for the low temperatures is circulation of seawater along normal faults in the unstable prism.

Runoff sources and flowpaths in a partially burned, upland boreal catchment underlain by permafrost

USGS Publications Warehouse

Koch, Joshua C.; Kikuchi, Colin P.; Wickland, Kimberly P.; Schuster, Paul

2014-01-01

Boreal soils in permafrost regions contain vast quantities of frozen organic material that is released to terrestrial and aquatic environments via subsurface flowpaths as permafrost thaws. Longer flowpaths may allow chemical reduction of solutes, nutrients, and contaminants, with implications for greenhouse gas emissions and aqueous export. Predicting boreal catchment runoff is complicated by soil heterogeneities related to variability in active layer thickness, soil type, fire history, and preferential flow potential. By coupling measurements of permeability, infiltration potential, and water chemistry with a stream chemistry end member mixing model, we tested the hypothesis that organic soils and burned slopes are the primary sources of runoff, and that runoff from burned soils is greater due to increased hydraulic connectivity. Organic soils were more permeable than mineral soils, and 25% of infiltration moved laterally upon reaching the organic-mineral soil boundary on unburned hillslopes. A large portion of the remaining water infiltrated into deeper, less permeable soils. In contrast, burned hillslopes displayed poorly defined soil horizons, allowing rapid, mineral-rich runoff through preferential pathways at various depths. On the catchment scale, mineral/organic runoff ratios averaged 1.6 and were as high as 5.2 for an individual storm. Our results suggest that burned soils are the dominant source of water and solutes reaching the stream in summer, whereas unburned soils may provide longer term storage and residence times necessary for production of anaerobic compounds. These results are relevant to predicting how boreal catchment drainage networks and stream export will evolve given continued warming and altered fire regimes.

Transverse Chemotactic Migration of Bacteria from High to Low Permeability Regions in a Dual Permeability Porous Microfluidic Device

NASA Astrophysics Data System (ADS)

Singh, R.; Olson, M. S.

2011-12-01

Low permeability regions sandwiched between high permeability regions such as clay lenses are difficult to treat using conventional treatment methods. Trace concentrations of contaminants such as non-aqueous phase liquids (NAPLs) remain trapped in these regions and over the time diffuse out into surrounding water thereby acting as a long term source of groundwater contamination. Bacterial chemotaxis (directed migration toward a contaminant source), may be helpful in enhancing bioremediation of such contaminated sites. This study is focused on simulating a two-dimensional dual-permeability groundwater contamination scenario using microfluidic devices and evaluating transverse chemotactic migration of bacteria from high to low permeability regions. A novel bi-layer polydimethylsiloxane (PDMS) microfluidic device was fabricated using photolithography and soft lithography techniques to simulate contamination of a dual- permeability region due to leakage from an underground storage tank into a low permeability region. This device consists of a porous channel through which a bacterial suspension (Escherchia Coli HCB33) is flown and another channel for injecting contaminant/chemo-attractant (DL-aspertic acid) into the porous channel. The pore arrangement in the porous channel contains a 2-D low permeability region surrounded by high permeability regions on both sides. Experiments were performed under chemotactic and non-chemotactic (replacing attractant with buffer solution in the non porous channel) conditions. Images were captured in transverse pore throats at cross-sections 4.9, 9.8, and 19.6 mm downstream from the attractant injection point and bacteria were enumerated in the middle of each pore throat. Bacterial chemotaxis was quantified in terms of the change in relative bacterial counts in each pore throat at cross-sections 9.8 and 19.6 mm with respect to counts at the cross-section at 4.9 mm. Under non-chemotactic conditions, relative bacterial count was observed to decrease at 9.8 mm and 19.6 mm cross-sections in low permeability regions due to dilution with the injectate from the non-porous channel (Figure 1). However, relative bacterial counts increased in the low permeability region at both downstream cross-sections under chemotactic conditions. A large increase in relative bacterial count in the pore throats just outside the low permeability region was also observed at both cross-sections (Figure 1). The bacterial chemotactic response was observed to decrease linearly with increasing Darcy velocity and at flow rate 0.220 mm/s the chemotactic effect was offset by the advective flow in the porous channel.

Exfoliated BN shell-based high-frequency magnetic core-shell materials.

PubMed

Zhang, Wei; Patel, Ketan; Ren, Shenqiang

2017-09-14

The miniaturization of electric machines demands high frequency magnetic materials with large magnetic-flux density and low energy loss to achieve a decreased dimension of high rotational speed motors. Herein, we report a solution-processed high frequency magnetic composite (containing a nanometal FeCo core and a boron nitride (BN) shell) that simultaneously exhibits high electrical resistivity and magnetic permeability. The frequency dependent complex initial permeability and the mechanical robustness of nanocomposites are intensely dependent on the content of BN insulating phase. The results shown here suggest that insulating magnetic nanocomposites have potential for application in next-generation high-frequency electric machines with large electrical resistivity and permeability.

The complexity of intestinal permeability: Assigning the correct BCS classification through careful data interpretation.

PubMed

Zur, Moran; Hanson, Allison S; Dahan, Arik

2014-09-30

While the solubility parameter is fairly straightforward when assigning BCS classification, the intestinal permeability (Peff) is more complex than generally recognized. In this paper we emphasize this complexity through the analysis of codeine, a commonly used antitussive/analgesic drug. Codeine was previously classified as a low-permeability compound, based on its lower LogP compared to metoprolol, a marker for the low-high permeability class boundary. In contrast, high fraction of dose absorbed (Fabs) was reported for codeine, which challenges the generally recognized Peff-Fabs correlation. The purpose of this study was to clarify this ambiguity through elucidation of codeine's BCS solubility/permeability class membership. Codeine's BCS solubility class was determined, and its intestinal permeability throughout the small intestine was investigated, both in vitro and in vivo in rats. Codeine was found to be unequivocally a high-solubility compound. All in vitro studies indicated that codeine's permeability is higher than metoprolol's. In vivo studies in rats showed similar permeability for both drugs throughout the entire small-intestine. In conclusion, codeine was found to be a BCS Class I compound. No Peff-Fabs discrepancy is involved in its absorption; rather, it reflects the risk of assigning BCS classification based on merely limited physicochemical characteristics. A thorough investigation using multiple experimental methods is prudent before assigning a BCS classification, to avoid misjudgment in various settings, e.g., drug discovery, formulation design, drug development and regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication

PubMed Central

Morosky, Stefanie; Lennemann, Nicholas J.

2016-01-01

ABSTRACT Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. IMPORTANCE Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of BPIFB6 expression correlates with pronounced defects in the secretory pathway and greatly reduces the replication of CVB, PV, and EV71. Our results thus identify a novel host cell therapeutic target whose function could be targeted to alter enterovirus replication. PMID:26962226

BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication.

PubMed

Morosky, Stefanie; Lennemann, Nicholas J; Coyne, Carolyn B

2016-05-15

Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of BPIFB6 expression correlates with pronounced defects in the secretory pathway and greatly reduces the replication of CVB, PV, and EV71. Our results thus identify a novel host cell therapeutic target whose function could be targeted to alter enterovirus replication. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Preventive effect of a high fluoride toothpaste and arginine-carbonate toothpaste on dentinal tubules exposure followed by acid challenge: a dentine permeability evaluation

PubMed Central

2014-01-01

Background Considering the current high use of high fluoride toothpastes, the aim of the study was to quantify alterations in the root dentine permeability submitted to treatment with a high fluoride toothpaste and 8% arginine, calcium carbonate, sodium monofluorophosphate toothpaste as a preventive treatment for dentinal tubules exposure followed by acid challenge. Methods Thirty-third molars were sectioned below the cementoenamel. The root segments were connected to a hydraulic pressure apparatus to measure dentine permeability after the following sequential steps (n = 10 per group): I) Baseline; II) treatment with phosphoric acid for 30 s (maximum permeability); III) Toothbrushing (1 min) according to the experimental groups (G1- control; G2- 5000 ppm fluoride toothpaste; G3- 8% arginine-calcium carbonate toothpaste); IV) acid challenge for 5 min (orange juice). The data were converted into percentage, considering stage II as 100%. Results The results have shown a statistically significant decreasing on dentine permeability after treatment with toothpaste (Friedman test and Dunn’s post hoc test). Comparison among groups demonstrated a high increasing on dentine permeability when acid challenge was performed after toothbrushing with distilled water (control group) (Kruskal-Wallis and Dunn’s post hoc test). Conclusion The toothpaste treatment may provide sufficient resistance on dentine surface, preventing dentinal tubules exposure after acid challenge. PMID:24958423

VEGF increases paracellular permeability in brain endothelial cells via upregulation of EphA2.

PubMed

Miao, Ziwei; Dong, Yanbin; Fang, Wengang; Shang, Deshu; Liu, Dongxin; Zhang, Ke; Li, Bo; Chen, Yu-Hua

2014-05-01

Neurological disorders are associated with an increase in the permeability of human brain microvascular endothelial cells (HBMEC). Our previous findings have indicated that EphA2 could increase the permeability of HBMEC. Recent evidence has linked EphA2 and vascular endothelial growth factor (VEGF) to abnormalities in the vascular response. However, it is unclear whether EphA2 is involved in the VEGF-induced changes in the permeability of HBMEC. Here, changes in permeability were determined by measuring transendothelial electrical resistance (TEER) and the flux of FITC-dextran. We found that knockdown of EphA2 in HBMEC abolished the VEGF-induced reduction in TEER and increase in flux of fluorescent dextran. Moreover, VEGF-induced redistribution of ZO-1 and the recruitment of detergent-soluble occludin and claudin-5 were also prevented. Further results showed that VEGF increased EphA2 expression in a time- and dose-dependent manner, which was inhibited by a neutralizing antibody against VEGFR2 or SU1498. VEGF-induced EphA2 expression was suppressed in the brain endothelium following treatments with the PI3K inhibitor LY294002, Akt inhibitor or transfection with the dominant-negative PI3K mutants (Δp110). Similar results were obtained when ERK1/2 activation was inhibited by PD98059 or ERK1/2 siRNA transfection. Our data suggest that VEGF upregulates the expression of EphA2 in HBMEC through binding to VEGFR2 and subsequently activating the intracellular PI3K/Akt and ERK1/2 signaling pathways, which contribute to an increase in paracellular permeability. These data reveal a novel role for VEGF as a regulator of EphA2 expression in the brain endothelial cells and provide insights into the molecular mechanisms of VEGF-mediated changes in paracellular permeability. Copyright © 2014 Wiley Periodicals, Inc.

Plasma Membrane Ca2+-Permeable Channels are Differentially Regulated by Ethylene and Hydrogen Peroxide to Generate Persistent Plumes of Elevated Cytosolic Ca2+ During Transfer Cell Trans-Differentiation.

PubMed

Zhang, Hui-ming; van Helden, Dirk F; McCurdy, David W; Offler, Christina E; Patrick, John W

2015-09-01

The enhanced transport capability of transfer cells (TCs) arises from their ingrowth wall architecture comprised of a uniform wall on which wall ingrowths are deposited. The wall ingrowth papillae provide scaffolds to amplify plasma membranes that are enriched in nutrient transporters. Using Vicia faba cotyledons, whose adaxial epidermal cells spontaneously and rapidly (hours) undergo a synchronous TC trans-differentiation upon transfer to culture, has led to the discovery of a cascade of inductive signals orchestrating deposition of ingrowth wall papillae. Auxin-induced ethylene biosynthesis initiates the cascade. This in turn drives a burst in extracellular H2O2 production that triggers uniform wall deposition. Thereafter, a persistent and elevated cytosolic Ca(2+) concentration, resulting from Ca(2+) influx through plasma membrane Ca(2+)-permeable channels, generates a Ca(2+) signal that directs formation of wall ingrowth papillae to specific loci. We now report how these Ca(2+)-permeable channels are regulated using the proportionate responses in cytosolic Ca(2+) concentration as a proxy measure of their transport activity. Culturing cotyledons on various combinations of pharmacological agents allowed the regulatory influence of each upstream signal on Ca(2+) channel activity to be evaluated. The findings demonstrated that Ca(2+)-permeable channel activity was insensitive to auxin, but up-regulated by ethylene through two independent routes. In one route ethylene acts directly on Ca(2+)-permeable channel activity at the transcriptional and post-translational levels, through an ethylene receptor-dependent pathway. The other route is mediated by an ethylene-induced production of extracellular H2O2 which then acts translationally and post-translationally to up-regulate Ca(2+)-permeable channel activity. A model describing the differential regulation of Ca(2+)-permeable channel activity is presented. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Quantifying Glomerular Permeability of Fluorescent Macromolecules Using 2-Photon Microscopy in Munich Wistar Rats

PubMed Central

Sandoval, Ruben M.; Molitoris, Bruce A.

2013-01-01

Kidney diseases involving urinary loss of large essential macromolecules, such as serum albumin, have long been thought to be caused by alterations in the permeability barrier comprised of podocytes, vascular endothelial cells, and a basement membrane working in unison. Data from our laboratory using intravital 2-photon microscopy revealed a more permeable glomerular filtration barrier (GFB) than previously thought under physiologic conditions, with retrieval of filtered albumin occurring in an early subset of cells called proximal tubule cells (PTC)1,2,3. Previous techniques used to study renal filtration and establishing the characteristic of the filtration barrier involved micropuncture of the lumen of these early tubular segments with sampling of the fluid content and analysis4. These studies determined albumin concentration in the luminal fluid to be virtually non-existent; corresponding closely to what is normally detected in the urine. However, characterization of dextran polymers with defined sizes by this technique revealed those of a size similar to serum albumin had higher levels in the tubular lumen and urine; suggesting increased permeability5. Herein is a detailed outline of the technique used to directly visualize and quantify glomerular fluorescent albumin permeability in vivo. This method allows for detection of filtered albumin across the filtration barrier into Bowman's space (the initial chamber of urinary filtration); and also allows quantification of albumin reabsorption by proximal tubules and visualization of subsequent albumin transcytosis6. The absence of fluorescent albumin along later tubular segments en route to the bladder highlights the efficiency of the retrieval pathway in the earlier proximal tubule segments. Moreover, when this technique was applied to determine permeability of dextrans having a similar size to albumin virtually identical permeability values were reported2. These observations directly support the need to expand the focus of many proteinuric renal diseases to included alterations in proximal tubule cell reclamation. PMID:23628966

Movement of NH3 through the human urea transporter B: a new gas channel

PubMed Central

Musa-Aziz, Raif; Enkavi, Giray; Mahinthichaichan, P.; Tajkhorshid, Emad; Boron, Walter F.

2013-01-01

Aquaporins and Rh proteins can function as gas (CO2 and NH3) channels. The present study explores the urea, H2O, CO2, and NH3 permeability of the human urea transporter B (UT-B) (SLC14A1), expressed in Xenopus oocytes. We monitored urea uptake using [14C]urea and measured osmotic water permeability (Pf) using video microscopy. To obtain a semiquantitative measure of gas permeability, we used microelectrodes to record the maximum transient change in surface pH (ΔpHS) caused by exposing oocytes to 5% CO2/33 mM HCO3− (pHS increase) or 0.5 mM NH3/NH4+ (pHS decrease). UT-B expression increased oocyte permeability to urea by >20-fold, and Pf by 8-fold vs. H2O-injected control oocytes. UT-B expression had no effect on the CO2-induced ΔpHS but doubled the NH3-induced ΔpHS. Phloretin reduced UT-B-dependent urea uptake (Jurea*) by 45%, Pf* by 50%, and (−ΔpHS*)NH3 by 70%. p-Chloromercuribenzene sulfonate reduced Jurea* by 25%, Pf* by 30%, and (ΔpHS*)NH3 by 100%. Molecular dynamics (MD) simulations of membrane-embedded models of UT-B identified the monomeric UT-B pores as the main conduction pathway for both H2O and NH3 and characterized the energetics associated with permeation of these species through the channel. Mutating each of two conserved threonines lining the monomeric urea pores reduced H2O and NH3 permeability. Our data confirm that UT-B has significant H2O permeability and for the first time demonstrate significant NH3 permeability. Thus the UTs become the third family of gas channels. Inhibitor and mutagenesis studies and results of MD simulations suggest that NH3 and H2O pass through the three monomeric urea channels in UT-B. PMID:23552862

Play-fairway analysis for geothermal exploration: Examples from the Great Basin, western USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siler, Drew L; Faulds, James E

2013-10-27

Elevated permeability within fault systems provides pathways for circulation of geothermal fluids. Future geothermal development depends on precise and accurate location of such fluid flow pathways in order to both accurately assess geothermal resource potential and increase drilling success rates. The collocation of geologic characteristics that promote permeability in a given geothermal system define the geothermal ‘fairway’, the location(s) where upflow zones are probable and where exploration efforts including drilling should be focused. We define the geothermal fairway as the collocation of 1) fault zones that are ideally oriented for slip or dilation under ambient stress conditions, 2) areas withmore » a high spatial density of fault intersections, and 3) lithologies capable of supporting dense interconnected fracture networks. Areas in which these characteristics are concomitant with both elevated temperature and fluids are probable upflow zones where economic-scale, sustainable temperatures and flow rates are most likely to occur. Employing a variety of surface and subsurface data sets, we test this ‘play-fairway’ exploration methodology on two Great Basin geothermal systems, the actively producing Brady’s geothermal system and a ‘greenfield’ geothermal prospect at Astor Pass, NV. These analyses, based on 3D structural and stratigraphic framework models, reveal subsurface characteristics about each system, well beyond the scope of standard exploration methods. At Brady’s, the geothermal fairways we define correlate well with successful production wells and pinpoint several drilling targets for maintaining or expanding production in the field. In addition, hot-dry wells within the Brady’s geothermal field lie outside our defined geothermal fairways. At Astor Pass, our play-fairway analysis provides for a data-based conceptual model of fluid flow within the geothermal system and indicates several targets for exploration drilling.« less

Hydrogen Permeability of Incoloy 800H, Inconel 617, and Haynes 230 Alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pattrick Calderoni

A potential issue in the design of the NGNP reactor and high-temperature components is the permeation of fission generated tritium and hydrogen product from downstream hydrogen generation through high-temperature components. Such permeation can result in the loss of fission-generated tritium to the environment and the potential contamination of the helium coolant by permeation of product hydrogen into the coolant system. The issue will be addressed in the engineering design phase, and requires knowledge of permeation characteristics of the candidate alloys. Of three potential candidates for high-temperature components of the NGNP reactor design, the hydrogen permeability has been documented well onlymore » for Incoloy 800H, but at relatively high partial pressures of hydrogen. Hydrogen permeability data have been published for Inconel 617, but only in two literature reports and for partial pressures of hydrogen greater than one atmosphere, far higher than anticipated in the NGNP reactor. The hydrogen permeability of Haynes 230 has not been published. To support engineering design of the NGNP reactor components, the hydrogen permeability of Inconel 617 and Haynes 230 were determined using a measurement system designed and fabricated at the Idaho National Laboratory. The performance of the system was validated using Incoloy 800H as reference material, for which the permeability has been published in several journal articles. The permeability of Incoloy 800H, Inconel 617 and Haynes 230 was measured in the temperature range 650 to 950 °C and at hydrogen partial pressures of 10-3 and 10-2 atm, substantially lower pressures than used in the published reports. The measured hydrogen permeability of Incoloy 800H and Inconel 617 were in good agreement with published values obtained at higher partial pressures of hydrogen. The hydrogen permeability of Inconel 617 and Haynes 230 were similar, about 50% greater than for Incoloy 800H and with similar temperature dependence.« less

NHERF1 and CFTR restore tight junction organisation and function in cystic fibrosis airway epithelial cells: role of ezrin and the RhoA/ROCK pathway.

PubMed

Castellani, Stefano; Guerra, Lorenzo; Favia, Maria; Di Gioia, Sante; Casavola, Valeria; Conese, Massimo

2012-11-01

Tight junctions (TJs) restrict the transit of ions and molecules through the paracellular route and act as a barrier to regulate access of inflammatory cells into the airway lumen. The pathophysiology of cystic fibrosis (CF) lung disease is characterised by abnormal ion and fluid transport across the epithelium and polymorphonuclear (PMN) leukocyte-dominated inflammatory response. Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) is a protein involved in PKA-dependent activation of CFTR by interacting with CFTR via its PDZ domains and with ezrin via its C-terminal domain. We have previously found that the NHERF1-overexpression dependent rescue CFTR-dependent chloride secretion is due to the re-organisation of the actin cytoskeleton network induced by the formation of the multiprotein complex NHERF1-RhoA-ezrin-actin. In this context, we here studied whether NHERF1 and CFTR are involved in the organisation and function of TJs. F508del CFBE41o⁻ monolayers presented nuclear localisation of zonula occludens (ZO-1) and occludin as well as disorganisation of claudin 1 and junction-associated adhesion molecule 1 as compared with wild-type 16HBE14o⁻ monolayers, paralleled by increased permeability to dextrans and PMN transmigration. Overexpression of either NHERF1 or CFTR in CFBE41o⁻ cells rescued TJ proteins to their proper intercellular location and decreased permeability and PMN transmigration, while this effect was not achieved by overexpressing either NHERF1 deprived of ezrin-binding domain. Further, expression of a phospho-dead ezrin mutant, T567A, increased permeability in both 16HBE14o⁻ cells and in a CFBE clone stably overexpressing NHERF1 (CFBE/sNHERF1), whereas a constitutively active form of ezrin, T567D, achieved the opposite effect in CFBE41o⁻ cells. A dominant-negative form of RhoA (RhoA-N19) also disrupted ZO-1 localisation at the intercellular contacts dislodging it to the nucleus and increased permeability in CFBE/sNHERF1. The inhibitor Y27632 of Rho kinase (ROCK) increased permeability as well. Overall, these data suggest a significant role for the multiprotein complex CFTR-NHERF1-ezrin-actin in maintaining TJ organisation and barrier function, and suggest that the RhoA/ROCK pathway is involved.

Experimental Microfracture Permeability Development in Crystalline Rocks Under Different Tectonic Stress Regimes

NASA Astrophysics Data System (ADS)

Faulkner, D. R.; Armitage, P. J.

2011-12-01

Geothermal fields rely on permeable fracture networks that can act for significant periods of time. In crystalline rocks, permeability may be stimulated by injections of fluid pressure at depth. We show how high-pressure laboratory experiments can be used to quantify the effects of different stress states on the permeability of two rocks; Darley Dale sandstone (~10-16 m2 permeability) and Westerly granite (~10-20 m2 permeability). It is well known that microfractures start to grow at stresses around one half of the failure stress. Failure in the experiments was reproduced in several ways: (1) by fixing σ3 and increasing σ1 - equivalent to a compressive or strike-slip tectonic regime (2) by fixing σ1 and decreasing σ3 - equivalent to an extensional tectonic regime (3) by increasing the pore fluid pressure at a fixed differential stress to simulate high pore fluid pressure failure, and (4) by fixing the mean stress while increasing σ1 and decreasing σ3 in sympathy. Permeability was monitored during all of these tests. From these tests we are able to quantify the relative contributions of mean stress, differential stress and pore fluid pressure on the permeability in the pre-failure region. This provides key data on the development of microfracture permeability that might be produced during the stimulation of geothermal fields during injection within different tectonic environments.

The protective effect of supplemental calcium on colonic permeability depends on a calcium phosphate-induced increase in luminal buffering capacity.

PubMed

Schepens, Marloes A A; ten Bruggencate, Sandra J M; Schonewille, Arjan J; Brummer, Robert-Jan M; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M J

2012-04-01

An increased intestinal permeability is associated with several diseases. Previously, we have shown that dietary Ca decreases colonic permeability in rats. This might be explained by a calcium-phosphate-induced increase in luminal buffering capacity, which protects against an acidic pH due to microbial fermentation. Therefore, we investigated whether dietary phosphate is a co-player in the effect of Ca on permeability. Rats were fed a humanised low-Ca diet, or a similar diet supplemented with Ca and containing either high, medium or low phosphate concentrations. Chromium-EDTA was added as an inert dietary intestinal permeability marker. After dietary adaptation, short-chain fructo-oligosaccharides (scFOS) were added to all diets to stimulate fermentation, acidify the colonic contents and induce an increase in permeability. Dietary Ca prevented the scFOS-induced increase in intestinal permeability in rats fed medium- and high-phosphate diets but not in those fed the low-phosphate diet. This was associated with higher faecal water cytotoxicity and higher caecal lactate levels in the latter group. Moreover, food intake and body weight during scFOS supplementation were adversely affected by the low-phosphate diet. Importantly, luminal buffering capacity was higher in rats fed the medium- and high-phosphate diets compared with those fed the low-phosphate diet. The protective effect of dietary Ca on intestinal permeability is impaired if dietary phosphate is low. This is associated with a calcium phosphate-induced increase in luminal buffering capacity. Dragging phosphate into the colon and thereby increasing the colonic phosphate concentration is at least part of the mechanism behind the protective effect of Ca on intestinal permeability.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Decker, A.D.; Kuuskraa, V.A.; Klawitter, A.L.

Recurrent basement faulting is the primary controlling mechanism for aligning and compartmentalizing upper Cretaceous aged tight gas reservoirs of the San Juan and Piceance Basins. Northwest trending structural lineaments that formed in conjunction with the Uncompahgre Highlands have profoundly influenced sedimentation trends and created boundaries for gas migration; sealing and compartmentalizing sedimentary packages in both basins. Fractures which formed over the structural lineaments provide permeability pathways which allowing gas recovery from otherwise tight gas reservoirs. Structural alignments and associated reservoir compartments have been accurately targeted by integrating advanced remote sensing imagery, high resolution aeromagnetics, seismic interpretation, stratigraphic mapping and dynamicmore » structural modelling. This unifying methodology is a powerful tool for exploration geologists and is also a systematic approach to tight gas resource assessment in frontier basins.« less

Structural controls on fluid circulation at the Caviahue-Copahue Volcanic Complex (CCVC) geothermal area (Chile-Argentina), revealed by soil CO2 and temperature, self-potential, and helium isotopes

NASA Astrophysics Data System (ADS)

Roulleau, Emilie; Bravo, Francisco; Pinti, Daniele L.; Barde-Cabusson, Stéphanie; Pizarro, Marcela; Tardani, Daniele; Muñoz, Carlos; Sanchez, Juan; Sano, Yuji; Takahata, Naoto; de la Cal, Federico; Esteban, Carlos; Morata, Diego

2017-07-01

Natural geothermal systems are limited areas characterized by anomalously high heat flow caused by recent tectonic or magmatic activity. The heat source at depth is the result of the emplacement of magma bodies, controlled by the regional volcano-tectonic setting. In contrast, at a local scale a well-developed fault-fracture network favors the development of hydrothermal cells, and promotes the vertical advection of fluids and heat. The Southern Volcanic Zone (SVZ), straddling Chile and Argentina, has an important, yet unexplored and undeveloped geothermal potential. Studies on the lithological and tectonic controls of the hydrothermal circulation are therefore important for a correct assessment of the geothermal potential of the region. Here, new and dense self-potential (SP), soil CO2 and temperature (T) measurements, and helium isotope data measured in fumaroles and thermal springs from the geothermal area located in the north-eastern flank of the Copahue volcanic edifice, within the Caviahue Caldera (the Caviahue-Copahue Volcanic Complex - CCVC) are presented. Our results allowed to the constraint of the structural origin of the active thermal areas and the understanding of the evolution of the geothermal system. NE-striking faults in the area, characterized by a combination of SP, CO2, and T maxima and high 3He/4He ratios (up to 8.16 ± 0.21Ra, whereas atmospheric Ra is 1.382 × 10- 6), promote the formation of vertical permeability preferential pathways for fluid circulation. WNW-striking faults represent low-permeability pathways for hydrothermal fluid ascent, but promote infiltration of meteoric water at shallow depths, which dilute the hydrothermal input. The region is scattered with SP, CO2, and T minima, representing self-sealed zones characterized by impermeable altered rocks at depth, which create local barriers for fluid ascent. The NE-striking faults seem to be associated with the upflowing zones of the geothermal system, where the boiling process produces a high vapor-dominated zone close to the surface, whereas the WNW-striking faults could act as a boundary of the Copahue geothermal area to the south.

The geothermal system of Caviahue-Copahue Volcanic Complex (Chile-Argentina): New insights from self-potential, soil CO2 degassing, temperature measurements and helium isotopes, with structural and fluid circulation implications.

NASA Astrophysics Data System (ADS)

Roulleau, Emilie; Bravo, Francisco; Barde-Cabusson, Stephanie; Pizarro, Marcela; Muños, Carlos; Sanchez, Juan; Tardani, Daniele; Sano, Yuji; Takahata, Naoto; de Cal, Federico; Esteban, Carlos

2016-04-01

Geothermal systems represent natural heat transfer engines in a confined volume of rock which are strongly influenced by the regional volcano-tectonic setting controlling the formation of shallow magmatic reservoirs, and by the local faults/fracture network, that permits the development of hydrothermal circulation cells and promote the vertical migration of fluids and heat. In the Southern Volcanic Zone of Chile-Argentina, geothermal resources occur in close spatial relationship with active volcanism along the Cordillera which is primarily controlled by the 1000 km long, NNE Liquiñe-Ofqui Fault Zone (LOFZ), an intra-arc dextral strike-slip fault system, associated with second-order intra-arc anisotropy of overall NE-SW (extensional) and NW-SE orientation (compressional). However there is still a lack of information on how fault network (NE and WNW strinking faults) and lithology control the fluid circulation. In this study, we propose new data of dense self-potential (SP), soil CO2 emanation and temperature (T) measurements within the geothermal area from Caviahue-Copahue Volcanic Complex (CCVC), coupled with helium isotopes ratios measured in fumaroles and thermal springs. We observe that inside the geothermal system the NE-striking faults, characterized by a combination of SP-CO2 and T maxima with high 3He/4He ratios (7.86Ra), promote the formation of high vertical permeability pathways for fluid circulation. Whereas, the WNW-striking faults represent low permeability pathways for hydrothermal fluids ascent associated with moderate 3He/4He ratios (5.34Ra), promoting the infiltration of meteoric water at shallow depth. These active zones are interspersed by SP-CO2- T minima, which represent self-sealed zones (e.g. impermeable altered rocks) at depth, creating a barrier inhibiting fluids rise. The NE-striking faults seem to be associated with the upflow zones of the geothermal system, where the boiling process produces a high vapor-dominated zone close to the surface. The WNW-striking faults seems to limit to the south the Copahue geothermal area.

An analytical model for inductively coupled implantable biomedical devices with ferrite rods.

PubMed

Theilmann, P T; Asbeck, P M

2009-02-01

Using approximations applicable to near field coupled implants simplified expressions for the complex mutual inductance of coaxial aligned coils with and without a cylindrical ferrite rod are derived. Experimental results for ferrite rods of various sizes and permeabilities are presented to verify the accuracy of this expression. An equivalent circuit model for the inductive link between an implant and power coil is then presented and used to investigate how ferrite size, permeability and loss affect the power available to the implant device. Enhancements in coupling provided by high frequency, low permeability nickel zinc rods are compared with low frequency high permeability manganese zinc rods.

Oxygen-Permeable, Hydrophobic Membranes of Silanized alpha-Al2O3

NASA Technical Reports Server (NTRS)

Atwater, James E.; Akse, James R.

2006-01-01

Membranes made of silanized alumina have been prepared and tested as prototypes of derivatized ceramic membranes that are both highly permeable to oxygen and hydrophobic. Improved oxygen-permeable, hydrophobic membranes would be attractive for use in several technological disciplines, including supporting high-temperature aqueousphase oxidation in industrial production of chemicals, oxygenation of aqueous streams for bioreactors, and oxygenation of blood during open-heart surgery and in cases of extreme pulmonary dysfunction. In comparison with organic polymeric oxygen-permeable membranes now commercially available, the derivatized ceramic membranes are more chemically robust, are capable of withstanding higher temperatures, and exhibit higher oxygen-diffusion coefficients.

Pacific Northwest (PNW) Hydrologic Landscape (HL) polygons and HL code

EPA Pesticide Factsheets

A five-letter hydrologic landscape code representing five indices of hydrologic form that are related to hydrologic function: climate, seasonality, aquifer permeability, terrain, and soil permeability. Each hydrologic assessment unit is classified by one of the 81 different five-letter codes representing these indices. Polygon features in this dataset were created by aggregating (dissolving boundaries between) adjacent, similarly-coded hydrologic assessment units. Climate Classes: V-Very wet, W-Wet, M-Moist, D-Dry, S-Semiarid, A-Arid. Seasonality Sub-Classes: w-Fall or winter, s-Spring. Aquifer Permeability Classes: H-High, L-Low. Terrain Classes: M-Mountain, T-Transitional, F-Flat. Soil Permeability Classes: H-High, L-Low.

Vacuum-driven power-free microfluidics utilizing the gas solubility or permeability of polydimethylsiloxane (PDMS).

PubMed

Xu, Linfeng; Lee, Hun; Jetta, Deekshitha; Oh, Kwang W

2015-10-21

Suitable pumping methods for flow control remain a major technical hurdle in the path of biomedical microfluidic systems for point-of-care (POC) diagnostics. A vacuum-driven power-free micropumping method provides a promising solution to such a challenge. In this review, we focus on vacuum-driven power-free microfluidics based on the gas solubility or permeability of polydimethylsiloxane (PDMS); degassed PDMS can restore air inside itself due to its high gas solubility or gas permeable nature. PDMS allows the transfer of air into a vacuum through it due to its high gas permeability. Therefore, it is possible to store or transfer air into or through the gas soluble or permeable PDMS in order to withdraw liquids into the embedded dead-end microfluidic channels. This article provides a comprehensive look at the physics of the gas solubility and permeability of PDMS, a systematic review of different types of vacuum-driven power-free microfluidics, and guidelines for designing solubility-based or permeability-based PDMS devices, alongside existing applications. Advanced topics and the outlook in using micropumping that utilizes the gas solubility or permeability of PDMS will be also discussed. We strongly recommend that microfluidics and lab-on-chip (LOC) communities harness vacuum energy to develop smart vacuum-driven microfluidic systems.

The influence of slip velocity and temperature on permeability during and after high-velocity fault slip

NASA Astrophysics Data System (ADS)

Tanikawa, W.; Mukoyoshi, H.; Tadai, O.; Hirose, T.; Lin, W.

2011-12-01

Fluid transport properties in fault zones play an important role in dynamic processes during large earthquakes. If the permeability in a fault zone is low, high pore-fluid pressures caused by thermal pressurization (Sibson, 1973) or shear-induced compaction (Blanpied et al., 1992) can lead to an apparent reduction of fault strength. Changes in porosity and permeability of fault rocks within a fault zone during earthquakes and the subsequent progressive recovery of these properties may have a large influence on earthquake recurrence (Sleep and Blanpied, 1992). A rotary shear apparatus was used to investigate changes of fluid transport properties in a fault zone by real-time measurement of gas flow rates during and after shearing of hollow sandstone and granite cylinders at various slip rates. Our apparatus measures permeability parallel to the slip plane in both the slip zone and wall rocks. In all cases, permeability decreased rapidly with an increase of friction, but recovered soon after slip, reaching a steady state within several tens of minutes. The rate of reduction of permeability increased with increasing slip velocity. Permeability did not recover to pre-slip levels after low-velocity tests but recovered to exceed them after high-velocity tests. Frictional heating of gases at the slip surface increased gas viscosity, which increased gas flow rate to produce an apparent permeability increase. The irreversible permeability changes of the low-velocity tests were caused by gouge formation due to wearing and smoothing of the slip surface. The increase of permeability after high-velocity tests was caused by mesoscale fracturing in response to rapid temperature rise. Changes of pore fluid viscosity contributed more to changes of flow rate than did permeability changes caused by shear deformation, although test results from different rocks and pore fluids might be different. References Blanpied, M.L., Lockner, D.A., Byerlee, J.D., 1992. An earthquake mechanism based on rapid sealing of faults. Nature 358, 574-576 Sibson, R.H., 1973. Interactions between temperature and pore fluid pressure during earthquake faulting: A mechanism for partial or total stress relief. Nature 243, 66-68. Sleep, N.H., Blanpied, M.L., 1992. Creep, compaction and the weak rheology of major faults. Nature 359, 687-692.

Identification of small-scale low and high permeability layers using single well forced-gradient tracer tests: fluorescent dye imaging and modelling at the laboratory-scale.

PubMed

Barns, Gareth L; Thornton, Steven F; Wilson, Ryan D

2015-01-01

Heterogeneity in aquifer permeability, which creates paths of varying mass flux and spatially complex contaminant plumes, can complicate the interpretation of contaminant fate and transport in groundwater. Identifying the location of high mass flux paths is critical for the reliable estimation of solute transport parameters and design of groundwater remediation schemes. Dipole flow tracer tests (DFTTs) and push-pull tests (PPTs) are single well forced-gradient tests which have been used at field-scale to estimate aquifer hydraulic and transport properties. In this study, the potential for PPTs and DFTTs to resolve the location of layered high- and low-permeability layers in granular porous media was investigated with a pseudo 2-D bench-scale aquifer model. Finite element fate and transport modelling was also undertaken to identify appropriate set-ups for in situ tests to determine the type, magnitude, location and extent of such layered permeability contrasts at the field-scale. The characteristics of flow patterns created during experiments were evaluated using fluorescent dye imaging and compared with the breakthrough behaviour of an inorganic conservative tracer. The experimental results show that tracer breakthrough during PPTs is not sensitive to minor permeability contrasts for conditions where there is no hydraulic gradient. In contrast, DFTTs are sensitive to the type and location of permeability contrasts in the host media and could potentially be used to establish the presence and location of high or low mass flux paths. Numerical modelling shows that the tracer peak breakthrough time and concentration in a DFTT is sensitive to the magnitude of the permeability contrast (defined as the permeability of the layer over the permeability of the bulk media) between values of 0.01-20. DFTTs are shown to be more sensitive to deducing variations in the contrast, location and size of aquifer layered permeability contrasts when a shorter central packer is used. However, larger packer sizes are more likely to be practical for field-scale applications, with fewer tests required to characterise a given aquifer section. The sensitivity of DFTTs to identify layered permeability contrasts was not affected by test flow rate. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigation of properties of high-performance fiber-reinforced concrete : very early strength, toughness, permeability, and fiber distribution : final report.

DOT National Transportation Integrated Search

2017-01-01

Concrete cracking, high permeability, and leaking joints allow for intrusion of harmful solutions, resulting in concrete deterioration and corrosion of reinforcement in structures. The development of durable, high-performance concretes with limited c...

Naringin attenuates MLC phosphorylation and NF-κB activation to protect sepsis-induced intestinal injury via RhoA/ROCK pathway.

PubMed

Li, Zhiling; Gao, Ming; Yang, Bingchang; Zhang, Huali; Wang, Kangkai; Liu, Zuoliang; Xiao, Xianzhong; Yang, Mingshi

2018-07-01

Sepsis is commonly associated with excessive stimulation of host immune system and result in multi-organ failure dysfunction. Naringin has been reported to exhibit a variety of biological effects. The present study aimed to investigate the protective effect of naringin on sepsis-induced injury of intestinal barrier function in vivo and in vitro. Mice were randomly divided into 4 groups named sham (n = 20), CLP + vehicle (n = 20), CLP + NG (30 mg/kg) (n = 20) and CLP + NG (60 mg/kg) (n = 20) groups. Sepsis was induced by cecal ligation and puncture (CLP). H&E staining and transmission electron microscopy (TEM) were performed to observe intestinal mucosal morphology. ELISA was used to determine the intestinal permeability and inflammatory response in vivo and in vitro. Western blot and RhoA activity assay were performed to determine the levels of tight junction proteins and the activation of indicated signaling pathways. MTT assay was used to determine cell viability. Naringin improved survival rate of CLP mice and alleviated sepsis-induced intestinal mucosal injury. Furthermore, naringin improved impaired intestinal permeability and inhibited the release of TNF-α and IL-6, while increased IL-10 level in CLP mice and lipopolysaccharide (LPS)-stimulated MODE-K cells in a dose-dependent manner. Naringin increased the expression of tight junction proteins ZO-1 and claudin-1 via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro. Naringin improved sepsis-induced intestinal injury via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro. Copyright © 2018. Published by Elsevier Masson SAS.

Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore

PubMed Central

Barrientos, Sebastian A.; Martinez, Nicolas W.; Yoo, Soonmoon; Jara, Juan S.; Zamorano, Sebastian; Hetz, Claudio; Twiss, Jeffery L.; Alvarez, Jaime; Court, Felipe A.

2011-01-01

Axonal degeneration is an active process that has been associated with neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. This degenerative process can cause permanent loss of function, so it represents a focus for neuroprotective strategies. Several signaling pathways are implicated in axonal degeneration, but identification of an integrative mechanism for this self-destructive process has remained elusive. Here, we show that rapid axonal degeneration triggered by distinct mechanical and toxic insults is dependent on the activation of the mitochondrial permeability transition pore (mPTP). Both pharmacological and genetic targeting of cyclophilin D, a functional component of the mPTP, protects severed axons and vincristine-treated neurons from axonal degeneration in ex vivo and in vitro mouse and rat model systems. These effects were observed in axons from both the peripheral and central nervous system. Our results suggest that the mPTP is a key effector of axonal degeneration, upon which several independent signaling pathways converge. Since axonal and synapse degeneration are increasingly considered early pathological events in neurodegeneration, our work identifies a potential target for therapeutic intervention in a wide variety of conditions that lead to loss of axons and subsequent functional impairment. PMID:21248121

An Overview of Pathways of Regulated Necrosis in Acute Kidney Injury.

PubMed

Kers, Jesper; Leemans, Jaklien C; Linkermann, Andreas

2016-05-01

Necrosis is the predominant form of regulated cell death in acute kidney injury (AKI) and represents results in the formation of casts that appear in the urine sedimentation, referred to as muddy brown casts, which are part of the diagnosis of AKI. Pathologists referred to this typical feature as acute tubular necrosis. We are only beginning to understand the dynamics and the molecular pathways that underlie such typical necrotic morphology. In this review, we provide an overview of candidate pathways and summarize the emerging evidence for the relative contribution of these pathways of regulated necrosis, such as necroptosis, ferroptosis, mitochondrial permeability transition-mediated regulated necrosis, parthanatos, and pyroptosis. Inhibitors of each of these pathways are available, and clinical trials may be started after the detection of the most promising drug targets, which will be discussed here. With the global burden of AKI in mind, inhibitiors of regulated necrosis represent promising means to prevent this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapid Assessment of Logging-Associated Sediment-Delivery Pathways in an Intensively-Managed Forested Watershed in the Southern Cascades, Northern California

NASA Astrophysics Data System (ADS)

Coe, D. B.; Wopat, M. A.; Lindsay, D.; Stanish, S.; Boone, M.; Beck, B.; Wyman, A.; Bull, J.

2012-12-01

The potential for water-quality impacts in intensively-managed forested watersheds depends partly upon the frequency of overland flow paths linking logging-related hillslope sediment sources to the channel network, as well as the volume of sediment delivered along these flow paths. In response to public concerns over perceived water-quality impacts from clearcut timber harvesting, the Battle Creek Task Force, composed of subject-matter experts from 4 different state agencies, performed a rapid assessment for visible evidence of sediment delivery pathways from multiple logging-associated features in the upper Battle Creek watershed - an area underlain predominantly by Holocene- and Late Pleistocene-aged volcanic rock types, with highly permeable soils, and relatively few streams. Logging-associated features were selected for assessment based on erosion potential and proximity to stream channels. Identified sediment-delivery pathways were then characterized by dominant erosion process and the relative magnitude of sediment delivery (i.e., low, moderate, and high) was estimated. Approximately 26 km of stream buffers adjacent to 55 clearcut harvest units were assessed, and the single detected instance of sediment delivery was found to be of low magnitude and the result of illegal encroachment by logging equipment into a 5-m wide stream-adjacent equipment-limitation zone. The proportion of sampled sites delivering sediment was found to be highest for tractor-stream crossings, followed by road-stream crossings, stream-adjacent road segments, stream-adjacent landings, and clearcut harvest units, respectively. All 5 tractor-stream crossings delivered sediment, but were generally delivering a low magnitude of sediment derived from sheetwash and rilling. Road-stream crossings (n=39) and stream-adjacent road segments (n=24) delivered observable sediment 69 and 67 percent of the time, respectively. The highest magnitudes of sediment delivery from roads were associated with substandard design or maintenance practices (e.g., poor road drainage) and/or poor location (e.g., roads less than 15 m from a stream), but the magnitude of sediment delivery was generally low or unobservable where Best Management Practices (BMPs) had been implemented. Conceptually, water-quality impacts are limited by the low density of streams in the watershed, relatively low hillslope gradients, relatively high permeability of the soils, and the implementation of BMPs. Assessment results suggest that direct water-quality impacts from overland flow paths in these types of watersheds are best minimized by disconnecting flow paths linking roads to streams, and by implementing BMPs.

CONCRETE BLOCKS' ADVERSE EFFECTS ON INDOOR AIR AND RECOMMENDED SOLUTIONS

EPA Science Inventory

Air infiltration through highly permeable concrete blocks can allow entry of various serious indoor air pollutants. An easy approach to avoiding these pollutants is to select a less–air-permeable concrete block. Tests show that air permeability of concrete blocks can vary by a fa...

Greater scaffold permeability promotes growth of osteoblastic cells in a perfused bioreactor.

PubMed

Fan, Jie; Jia, Xiaoling; Huang, Yan; Fu, Bingmei M; Fan, Yubo

2015-12-01

Pore size and porosity have been widely acknowledged as important structural factors in tissue-engineered scaffolds. In fact, scaffolds with similar pore size and porosity can provide important and varied permeability due to different pore shape, interconnectivity and tortuosity. However, the effects of scaffold permeability on seeded cells remains largely unknown during tissue regeneration in vitro. In this study, we measured the Darcy permeability (K) of tri-calcium phosphate scaffolds by distributed them into three groups: Low, Medium and High. As a result, the effects of scaffold permeability on cell proliferation, cellular activity and growth in the inner pores were investigated in perfused and static cultures in vitro. Results demonstrated that higher permeable scaffolds exhibited superior performance during bone regeneration in vitro and the advantages of higher scaffold permeability were amplified in perfused culture. Based on these findings, scaffold permeability should be considered in future scaffold fabrications. Copyright © 2013 John Wiley & Sons, Ltd.

Evolution of permeability and Biot coefficient at high mean stresses in high porosity sandstone

DOE PAGES

Ingraham, Mathew D.; Bauer, Stephen J.; Issen, Kathleen A.; ...

2017-05-01

A series of constant mean stress (CMS) and constant shear stress (CSS) tests were performed to investigate the evolution of permeability and Biot coefficient at high mean stresses in a high porosity reservoir analog (Castlegate sandstone). Permeability decreases as expected with increasing mean stress, from about 20 Darcy at the beginning of the tests to between 1.5 and 0.3 Darcy at the end of the tests (mean stresses up to 275 MPa). The application of shear stress causes permeability to drop below that of a hydrostatic test at the same mean stress. Results show a nearly constant rate decrease inmore » the Biot coefficient as the mean stress increases during hydrostatic loading, and as the shear stress increases during CMS loading. In conclusion, CSS tests show a stabilization of the Biot coefficient after the application of shear stress.« less

Evolution of permeability and Biot coefficient at high mean stresses in high porosity sandstone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ingraham, Mathew D.; Bauer, Stephen J.; Issen, Kathleen A.

A series of constant mean stress (CMS) and constant shear stress (CSS) tests were performed to investigate the evolution of permeability and Biot coefficient at high mean stresses in a high porosity reservoir analog (Castlegate sandstone). Permeability decreases as expected with increasing mean stress, from about 20 Darcy at the beginning of the tests to between 1.5 and 0.3 Darcy at the end of the tests (mean stresses up to 275 MPa). The application of shear stress causes permeability to drop below that of a hydrostatic test at the same mean stress. Results show a nearly constant rate decrease inmore » the Biot coefficient as the mean stress increases during hydrostatic loading, and as the shear stress increases during CMS loading. In conclusion, CSS tests show a stabilization of the Biot coefficient after the application of shear stress.« less

Superconducting magnet and fabrication method

NASA Technical Reports Server (NTRS)

Israelsson, Ulf E. (Inventor); Strayer, Donald M. (Inventor)

1994-01-01

A method of trapping a field in a block of superconductor material, includes providing (i) a block of material defining a bore, (ii) a high permeability core within the bore that defines a low reluctance path through the bore, (iii) a high permeability external structure on the exterior of the block of material that defines a low reluctance path between opposite ends of the core, and (iv) an electromagnet configured to apply a magnetic field around the high permeability core. The method proceeds by energizing the electromagnet to produce an applied magnetic field around the high permeability core, cooling the block of material sufficiently to render the block of material superconducting, de-energizing the electromagnet to result in a trapped magnetic field, and at least partially removing the low reluctance path defined by the core and the external structure in order to increase the magnetic flux density of the trapped magnetic field.

Learning from our failures in blood-brain permeability: what can be done for new drug discovery?

PubMed

Martel, Sylvain

2015-03-01

Many existing pharmaceuticals are rendered ineffective in the treatment of cerebral diseases due to a permeability barrier well known as the blood-brain barrier (BBB). Such barrier between the blood within brain capillaries and the extracellular fluid in brain tissue has motivated several approaches aimed at delivering therapeutics to the brain. These approaches rely on strategies that can be classified as molecular modifications, the use of BBB bypassing pathways, and BBB disruptions. Although several of these approaches that have been investigated so far show promising results, none has addressed the optimization of the ratio of the dose of the drug molecules that contributes to the therapeutic effects. As such, the extensive research efforts, such as prioritizing the enhancement of the BBB permeability alone is likely to fail to provide the best therapeutic effects for a given dose if prior systemic circulation is not avoided while enhancing the spatial targeting only to regions of the brain that need treatment. Hence, new therapeutics for the brain could be synthesized to take advantage of recent technologies for non-systemic delivery and spatially targeted brain uptake.

Improving the production of 22-hydroxy-23,24-bisnorchol-4-ene-3-one from sterols in Mycobacterium neoaurum by increasing cell permeability and modifying multiple genes.

PubMed

Xiong, Liang-Bin; Liu, Hao-Hao; Xu, Li-Qin; Sun, Wan-Ju; Wang, Feng-Qing; Wei, Dong-Zhi

2017-05-22

The strategy of modifying the sterol catabolism pathway in mycobacteria has been adopted to produce steroidal pharmaceutical intermediates, such as 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC), which is used to synthesize various steroids in the industry. However, the productivity is not desirable due to some inherent problems, including the unsatisfactory uptake rate and the low metabolic efficiency of sterols. The compact cell envelope of mycobacteria is a main barrier for the uptake of sterols. In this study, a combined strategy of improving the cell envelope permeability as well as the intracellular sterol metabolism efficiency was investigated to increase the productivity of 4-HBC. MmpL3, encoding a transmembrane transporter of trehalose monomycolate, is an important gene influencing the assembly of mycobacterial cell envelope. The disruption of mmpL3 in Mycobacterium neoaurum ATCC 25795 significantly enhanced the cell permeability by 23.4% and the consumption capacity of sterols by 15.6%. Therefore, the inactivation of mmpL3 was performed in a 4-HBC-producing strain derived from the wild type M. neoaurum and the 4-HBC production in the engineered strain was increased by 24.7%. Subsequently, to enhance the metabolic efficiency of sterols, four key genes, choM1, choM2, cyp125, and fadA5, involved in the sterol conversion pathway were individually overexpressed in the engineered mmpL3-deficient strain. The production of 4-HBC displayed the increases of 18.5, 8.9, 14.5, and 12.1%, respectively. Then, the more efficient genes (choM1, cyp125, and fadA5) were co-overexpressed in the engineered mmpL3-deficient strain, and the productivity of 4-HBC was ultimately increased by 20.3% (0.0633 g/L/h, 7.59 g/L 4-HBC from 20 g/L phytosterol) compared with its original productivity (0.0526 g/L/h, 6.31 g/L 4-HBC from 20 g/L phytosterol) in an industrial resting cell bio-transformation system. Increasing cell permeability combined with the co-overexpression of the key genes (cyp125, choM1, and fadA5) involved in the conversion pathway of sterol to 4-HBC was effective to enhance the productivity of 4-HBC. The strategy might also be useful for the conversion of sterol to other steroidal intermediates by mycobacteria.

Grain-size dynamics beneath mid-ocean ridges: Implications for permeability and melt extraction.

PubMed

Turner, Andrew J; Katz, Richard F; Behn, Mark D

2015-03-01

Grain size is an important control on mantle viscosity and permeability, but is difficult or impossible to measure in situ. We construct a two-dimensional, single phase model for the steady state mean grain size beneath a mid-ocean ridge. The mantle rheology is modeled as a composite of diffusion creep, dislocation creep, dislocation accommodated grain boundary sliding, and a plastic stress limiter. The mean grain size is calculated by the paleowattmeter relationship of Austin and Evans (2007). We investigate the sensitivity of our model to global variations in grain growth exponent, potential temperature, spreading-rate, and mantle hydration. We interpret the mean grain-size field in terms of its permeability to melt transport. The permeability structure due to mean grain size may be approximated as a high permeability region beneath a low permeability region. The transition between high and low permeability regions occurs across a boundary that is steeply inclined toward the ridge axis. We hypothesize that such a permeability structure generated from the variability of the mean grain size may focus melt toward the ridge axis, analogous to Sparks and Parmentier (1991)-type focusing. This focusing may, in turn, constrain the region where significant melt fractions are observed by seismic or magnetotelluric surveys. This interpretation of melt focusing via the grain-size permeability structure is consistent with MT observation of the asthenosphere beneath the East Pacific Rise. The grain-size field beneath MORs can vary over orders of magnitude The grain-size field affects the rheology and permeability of the asthenosphere The grain-size field may focus melt toward the ridge axis.

Analytical approximations for effective relative permeability in the capillary limit

NASA Astrophysics Data System (ADS)

Rabinovich, Avinoam; Li, Boxiao; Durlofsky, Louis J.

2016-10-01

We present an analytical method for calculating two-phase effective relative permeability, krjeff, where j designates phase (here CO2 and water), under steady state and capillary-limit assumptions. These effective relative permeabilities may be applied in experimental settings and for upscaling in the context of numerical flow simulations, e.g., for CO2 storage. An exact solution for effective absolute permeability, keff, in two-dimensional log-normally distributed isotropic permeability (k) fields is the geometric mean. We show that this does not hold for krjeff since log normality is not maintained in the capillary-limit phase permeability field (Kj=k·krj) when capillary pressure, and thus the saturation field, is varied. Nevertheless, the geometric mean is still shown to be suitable for approximating krjeff when the variance of ln⁡k is low. For high-variance cases, we apply a correction to the geometric average gas effective relative permeability using a Winsorized mean, which neglects large and small Kj values symmetrically. The analytical method is extended to anisotropically correlated log-normal permeability fields using power law averaging. In these cases, the Winsorized mean treatment is applied to the gas curves for cases described by negative power law exponents (flow across incomplete layers). The accuracy of our analytical expressions for krjeff is demonstrated through extensive numerical tests, using low-variance and high-variance permeability realizations with a range of correlation structures. We also present integral expressions for geometric-mean and power law average krjeff for the systems considered, which enable derivation of closed-form series solutions for krjeff without generating permeability realizations.

The investigation of parachute fabric permeability under an unsteady pressure differential

NASA Astrophysics Data System (ADS)

Rondeau, Nichole C.

An apparatus for assessing permeability of textiles subjected to time-varying pressure differentials is presented. A Computer Numerically Controlled Piston Permeability Apparatus (CNC-PPA) that can control the volume flow rate through a fabric has been designed and built. This test device has been developed in an effort to improve the understanding and design choices for aerodynamic decelerators. Preliminary results for a low permeability fabric (PIA-C-44378, Type IV) under both steady and unsteady loads are presented. The results from this investigation do indicate a small effect of unsteady pressure differential on the fabric permeability. The fabric permeability is slightly higher than the static permeability when the pressure differential is increasing with respect to time and the opposite is true when the pressure differential is decreasing. This change in permeability is more pronounced as the pressure is higher and the pressure changes more rapidly with respect to time, suggesting dynamic permeability likely affects highly unsteady phenomena such as parachute opening.

Models of regional habitat quality and connectivity for pumas (Puma concolor) in the southwestern United States.

PubMed

Dickson, Brett G; Roemer, Gary W; McRae, Brad H; Rundall, Jill M

2013-01-01

The impact of landscape changes on the quality and connectivity of habitats for multiple wildlife species is of global conservation concern. In the southwestern United States, pumas (Puma concolor) are a well distributed and wide-ranging large carnivore that are sensitive to loss of habitat and to the disruption of pathways that connect their populations. We used an expert-based approach to define and derive variables hypothesized to influence the quality, location, and permeability of habitat for pumas within an area encompassing the entire states of Arizona and New Mexico. Survey results indicated that the presence of woodland and forest cover types, rugged terrain, and canyon bottom and ridgeline topography were expected to be important predictors of both high quality habitat and heightened permeability. As road density, distance to water, or human population density increased, the quality and permeability of habitats were predicted to decline. Using these results, we identified 67 high quality patches across the study area, and applied concepts from electronic circuit theory to estimate regional patterns of connectivity among these patches. Maps of current flow among individual pairs of patches highlighted possible pinch points along two major interstate highways. Current flow summed across all pairs of patches highlighted areas important for keeping the entire network connected, regardless of patch size. Cumulative current flow was highest in Arizona north of the Colorado River and around Grand Canyon National Park, and in the Sky Islands region owing to the many small habitat patches present. Our outputs present a first approximation of habitat quality and connectivity for dispersing pumas in the southwestern United States. Map results can be used to help target finer-scaled analyses in support of planning efforts concerned with the maintenance of puma metapopulation structure, as well as the protection of landscape features that facilitate the dispersal process.

Models of Regional Habitat Quality and Connectivity for Pumas (Puma concolor) in the Southwestern United States

PubMed Central

Dickson, Brett G.; Roemer, Gary W.; McRae, Brad H.; Rundall, Jill M.

2013-01-01

The impact of landscape changes on the quality and connectivity of habitats for multiple wildlife species is of global conservation concern. In the southwestern United States, pumas (Puma concolor) are a well distributed and wide-ranging large carnivore that are sensitive to loss of habitat and to the disruption of pathways that connect their populations. We used an expert-based approach to define and derive variables hypothesized to influence the quality, location, and permeability of habitat for pumas within an area encompassing the entire states of Arizona and New Mexico. Survey results indicated that the presence of woodland and forest cover types, rugged terrain, and canyon bottom and ridgeline topography were expected to be important predictors of both high quality habitat and heightened permeability. As road density, distance to water, or human population density increased, the quality and permeability of habitats were predicted to decline. Using these results, we identified 67 high quality patches across the study area, and applied concepts from electronic circuit theory to estimate regional patterns of connectivity among these patches. Maps of current flow among individual pairs of patches highlighted possible pinch points along two major interstate highways. Current flow summed across all pairs of patches highlighted areas important for keeping the entire network connected, regardless of patch size. Cumulative current flow was highest in Arizona north of the Colorado River and around Grand Canyon National Park, and in the Sky Islands region owing to the many small habitat patches present. Our outputs present a first approximation of habitat quality and connectivity for dispersing pumas in the southwestern United States. Map results can be used to help target finer-scaled analyses in support of planning efforts concerned with the maintenance of puma metapopulation structure, as well as the protection of landscape features that facilitate the dispersal process. PMID:24367495

Mechanistic investigations into the species differences in pinometostat clearance: impact of binding to alpha-1-acid glycoprotein and permeability-limited hepatic uptake.

PubMed

Smith, Sherri A; Gagnon, Sandra; Waters, Nigel J

2017-03-01

1. The plasma clearance of the first-in-class DOT1L inhibitor, EPZ-5676 (pinometostat), was shown to be markedly lower in human compared to the preclinical species, mouse, rat and dog. 2. This led to vertical allometry where various interspecies scaling methods were applied to the data, with fold-errors between 4 and 13. We had previously reported the elimination and metabolic pathways of EPZ-5676 were similar across species. Therefore, the aim of this work was to explore the mechanistic basis for the species difference in clearance for EPZ-5676, focusing on other aspects of disposition. 3. The protein binding of EPZ-5676 in human plasma demonstrated a non-linear relationship suggesting saturable binding at physiologically relevant concentrations. Saturation of protein binding was not observed in plasma from preclinical species. Kinetic determinations using purified serum albumin and alpha-1-acid glycoprotein (AAG) confirmed that EPZ-5676 is a high affinity ligand for AAG with a dissociation constant (K d ) of 0.24 μM. 4. Permeability limited uptake was also considered since hepatocyte CL int was much lower in human relative to preclinical species. Passive unbound CL int for EPZ-5676 was estimated using a correlation analysis of logD and data previously reported on seven drugs in sandwich cultured human hepatocytes. 5. Incorporation of AAG binding and permeability limited hepatic uptake into the well-stirred liver model gave rise to a predicted clearance for EPZ-5676 within 2-fold of the observed value of 1.4 mL min -1  kg -1 . This analysis suggests that the marked species difference in EPZ-5676 clearance is driven by high affinity binding to human AAG as well as species-specific hepatic uptake invoking the role of transporters.

High Temperature Permeability of Carbon Cloth Phenolic Composite

NASA Technical Reports Server (NTRS)

Park, O. Y.; Lawrence, T. W.

2003-01-01

The carbon fiber phenolic resin composite material used for the RSRM nozzle insulator occasionally experiences problems during operation from pocketing or spalling-like erosion and lifting of plies into the char layer. This phenomenon can be better understood if the permeability of the material at elevated temperatures is well defined. This paper describes an experimental approach to determining high temperature permeability of the carbon phenolic material used as the RSRM nozzle liner material. Two different approaches were conducted independently using disk and bar type specimens with the designed permeability apparatus. The principle of the apparatus was to subject a test specimen to a high pressure differential and a heat supply and to monitor both the pressure and temperature variations resulting from gas penetration through the permeable wall between the two chambers. The bar types, especially designed to eliminate sealing difficulties at a high temperature environment, were directly exposed to real time temperature elevation from 22 C to 260 C during the test period. The disk types were pre-heat treated up to 300 C for 8 hours and cooled to room temperature before testing. Nonlinear variation of downstream pressure at a certain temperature range implied moisture release and matrix pyrolysis. Permeability was calculated using a semi-numerical model of quasi-steady state. The test results and the numerical model are discussed in the paper.

Investigation on porosity and permeability change of Mount Simon sandstone (Knox County, IN, USA) under geological CO 2 sequestration conditions: a numerical simulation approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Liwei; Soong, Yee; Dilmore, Robert M.

In this paper, a numerical model was developed to simulate reactive transport with porosity and permeability change of Mount Simon sandstone (samples from Knox County, IN) after 180 days of exposure to CO 2-saturated brine under CO 2 sequestration conditions. The model predicted formation of a high-porosity zone adjacent to the surface of the sample in contact with bulk brine, and a lower porosity zone just beyond that high-porosity zone along the path from sample/bulk brine interface to sample core. The formation of the high porosity zone was attributed to dissolution of quartz and muscovite/illite, while the formation of themore » lower porosity zone adjacent to the aforementioned high porosity zone was attributed to precipitation of kaolinite and feldspar. The model predicted a 40% permeability increase for the Knox sandstone sample after 180 days of exposure to CO 2-saturated brine, which was consistent with laboratory-measured permeability results. Model-predicted solution chemistry results were also found to be consistent with laboratory-measured solution chemistry data. Finally, initial porosity, initial feldspar content and the exponent n value (determined by pore structure and tortuosity) used in permeability calculations were three important factors affecting permeability evolution of sandstone samples under CO 2 sequestration conditions.« less

Investigation on porosity and permeability change of Mount Simon sandstone (Knox County, IN, USA) under geological CO 2 sequestration conditions: a numerical simulation approach

DOE PAGES

Zhang, Liwei; Soong, Yee; Dilmore, Robert M.

2016-01-14

In this paper, a numerical model was developed to simulate reactive transport with porosity and permeability change of Mount Simon sandstone (samples from Knox County, IN) after 180 days of exposure to CO 2-saturated brine under CO 2 sequestration conditions. The model predicted formation of a high-porosity zone adjacent to the surface of the sample in contact with bulk brine, and a lower porosity zone just beyond that high-porosity zone along the path from sample/bulk brine interface to sample core. The formation of the high porosity zone was attributed to dissolution of quartz and muscovite/illite, while the formation of themore » lower porosity zone adjacent to the aforementioned high porosity zone was attributed to precipitation of kaolinite and feldspar. The model predicted a 40% permeability increase for the Knox sandstone sample after 180 days of exposure to CO 2-saturated brine, which was consistent with laboratory-measured permeability results. Model-predicted solution chemistry results were also found to be consistent with laboratory-measured solution chemistry data. Finally, initial porosity, initial feldspar content and the exponent n value (determined by pore structure and tortuosity) used in permeability calculations were three important factors affecting permeability evolution of sandstone samples under CO 2 sequestration conditions.« less

Determination of hydrogen permeability in uncoated and coated superalloys

NASA Technical Reports Server (NTRS)

Bhattacharyya, S.; Vesely, E. J., Jr.; Hill, V. L.

1981-01-01

Hydrogen permeability, diffusivity, and solubility data were obtained for eight wrought and cast high temperature alloys over the range 650 to 815 C. Data were obtained for both uncoated alloys and wrought alloys coated with four commercially available coatings. Activation energies for permeability, diffusivity and solubility were calculated.

Neutrophil-derived 5′-Adenosine Monophosphate Promotes Endothelial Barrier Function via CD73-mediated Conversion to Adenosine and Endothelial A2B Receptor Activation

PubMed Central

Lennon, Paul F.; Taylor, Cormac T.; Stahl, Gregory L.; Colgan, Sean P.

1998-01-01

During episodes of inflammation, polymorphonuclear leukocyte (PMN) transendothelial migration has the potential to disturb vascular barrier function and give rise to intravascular fluid extravasation and edema. However, little is known regarding innate mechanisms that dampen fluid loss during PMN-endothelial interactions. Using an in vitro endothelial paracellular permeability model, we observed a PMN-mediated decrease in endothelial paracellular permeability. A similar decrease was elicited by cell-free supernatants from activated PMN (FMLP 10−6 M), suggesting the presence of a PMN-derived soluble mediator(s). Biophysical and biochemical analysis of PMN supernatants revealed a role for PMN-derived 5′-adenosine monophosphate (AMP) and its metabolite, adenosine, in modulation of endothelial paracellular permeability. Supernatants from activated PMN contained micromolar concentrations of bioactive 5′-AMP and adenosine. Furthermore, exposure of endothelial monolayers to authentic 5′-AMP and adenosine increased endothelial barrier function more than twofold in both human umbilical vein endothelial cells and human microvascular endothelial cells. 5′-AMP bioactivity required endothelial CD73-mediated conversion of 5′-AMP to adenosine via its 5′-ectonucleotidase activity. Decreased endothelial paracellular permeability occurred through adenosine A2B receptor activation and was accompanied by a parallel increase in intracellular cAMP. We conclude that activated PMN release soluble mediators, such as 5′-AMP and adenosine, that promote endothelial barrier function. During inflammation, this pathway may limit potentially deleterious increases in endothelial paracellular permeability and could serve as a basic mechanism of endothelial resealing during PMN transendothelial migration. PMID:9782120

Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton

PubMed Central

Parker, William H.; Rhea, Elizabeth Meredith; Qu, Zhi-Chao; Hecker, Morgan R.

2016-01-01

Vitamin C, or ascorbic acid, both tightens the endothelial permeability barrier in basal cells and also prevents barrier leak induced by inflammatory agents. Barrier tightening by ascorbate in basal endothelial cells requires nitric oxide derived from activation of nitric oxide synthase. Although ascorbate did not affect cyclic AMP levels in our previous study, there remains a question of whether it might activate downstream cyclic AMP-dependent pathways. In this work, we found in both primary and immortalized cultured endothelial cells that ascorbate tightened the endothelial permeability barrier by ∼30%. In human umbilical vein endothelial cells, this occurred at what are likely physiologic intracellular ascorbate concentrations. In so doing, ascorbate decreased measures of oxidative stress and also flattened the cells to increase cell-to-cell contact. Inhibition of downstream cyclic AMP-dependent proteins via protein kinase A did not prevent ascorbate from tightening the endothelial permeability barrier, whereas inhibition of Epac1 did block the ascorbate effect. Although Epac1 was required, its mediator Rap1 was not activated. Furthermore, ascorbate acutely stabilized microtubules during depolymerization induced by colchicine and nocodazole. Over several days in culture, ascorbate also increased the amount of stable acetylated α-tubulin. Microtubule stabilization was further suggested by the finding that ascorbate increased the amount of Epac1 bound to α-tubulin. These results suggest that physiologic ascorbate concentrations tighten the endothelial permeability barrier in unstimulated cells by stabilizing microtubules in a manner downstream of cyclic AMP that might be due both to increasing nitric oxide availability and to scavenging of reactive oxygen or nitrogen species. PMID:27605450

A high-performance dual-scale porous electrode for vanadium redox flow batteries

NASA Astrophysics Data System (ADS)

Zhou, X. L.; Zeng, Y. K.; Zhu, X. B.; Wei, L.; Zhao, T. S.

2016-09-01

In this work, we present a simple and cost-effective method to form a dual-scale porous electrode by KOH activation of the fibers of carbon papers. The large pores (∼10 μm), formed between carbon fibers, serve as the macroscopic pathways for high electrolyte flow rates, while the small pores (∼5 nm), formed on carbon fiber surfaces, act as active sites for rapid electrochemical reactions. It is shown that the Brunauer-Emmett-Teller specific surface area of the carbon paper is increased by a factor of 16 while maintaining the same hydraulic permeability as that of the original carbon paper electrode. We then apply the dual-scale electrode to a vanadium redox flow battery (VRFB) and demonstrate an energy efficiency ranging from 82% to 88% at current densities of 200-400 mA cm-2, which is record breaking as the highest performance of VRFB in the open literature.

Temperature dependence dynamical permeability characterization of magnetic thin film using near-field microwave microscopy

NASA Astrophysics Data System (ADS)

Hung, Le Thanh; Phuoc, Nguyen N.; Wang, Xuan-Cong; Ong, C. K.

2011-08-01

A temperature dependence characterization system of microwave permeability of magnetic thin film up to 5 GHz in the temperature range from room temperature up to 423 K is designed and fabricated as a prototype measurement fixture. It is based on the near field microwave microscopy technique (NFMM). The scaling coefficient of the fixture can be determined by (i) calibrating the NFMM with a standard sample whose permeability is known; (ii) by calibrating the NFMM with an established dynamic permeability measurement technique such as shorted microstrip transmission line perturbation method; (iii) adjusting the real part of the complex permeability at low frequency to fit the value of initial permeability. The algorithms for calculating the complex permeability of magnetic thin films are analyzed. A 100 nm thick FeTaN thin film deposited on Si substrate by sputtering method is characterized using the fixture. The room temperature permeability results of the FeTaN film agree well with results obtained from the established short-circuited microstrip perturbation method. Temperature dependence permeability results fit well with the Landau-Lifshitz-Gilbert equation. The temperature dependence of the static magnetic anisotropy H_K^{sta}, the dynamic magnetic anisotropy H_K^{dyn}, the rotational anisotropy Hrot, together with the effective damping coefficient αeff, ferromagnetic resonance fFMR, and frequency linewidth Δf of the thin film are investigated. These temperature dependent magnetic properties of the magnetic thin film are important to the high frequency applications of magnetic devices at high temperatures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beckingham, Lauren E.; Peters, Catherine A.; Um, Wooyong

Although the impact of subsurface geochemical reactions on porosity is relatively well understood, changes in permeability remain difficult to estimate. In this work, pore-network modeling was used to predict permeability based on pore- and pore-throat size distributions determined from analysis of 2D scanning electron microscopy (SEM) images of thin sections and 3D X-ray computed microtomography (CMT) data. The analyzed specimens were a Viking sandstone sample from the Alberta sedimentary basin and an experimental column of reacted Hanford sediments. For the column, a decrease in permeability due to mineral precipitation was estimated, but the permeability estimates were dependent on imaging techniquemore » and resolution. X-ray CT imaging has the advantage of reconstructing a 3D pore network while 2D SEM imaging can easily analyze sub-grain and intragranular variations in mineralogy. Pore network models informed by analyses of 2D and 3D images at comparable resolutions produced permeability esti- mates with relatively good agreement. Large discrepancies in predicted permeabilities resulted from small variations in image resolution. Images with resolutions 0.4 to 4 lm predicted permeabilities differ- ing by orders of magnitude. While lower-resolution scans can analyze larger specimens, small pore throats may be missed due to resolution limitations, which in turn overestimates permeability in a pore-network model in which pore-to-pore conductances are statistically assigned. Conversely, high-res- olution scans are capable of capturing small pore throats, but if they are not actually flow-conducting predicted permeabilities will be below expected values. In addition, permeability is underestimated due to misinterpreting surface-roughness features as small pore throats. Comparison of permeability pre- dictions with expected and measured permeability values showed that the largest discrepancies resulted from the highest resolution images and the best predictions of permeability will result from images between 2 and 4 lm resolution. To reduce permeability underestimation from analyses of high-resolu- tion images, a resolution threshold between 3 and 15 lm was found to be effective, but it is not known whether this range is applicable beyond the samples studied here.« less

Hereditary angioedema: a bradykinin-mediated swelling disorder.

PubMed

Björkqvist, Jenny; Sala-Cunill, Anna; Renné, Thomas

2013-03-01

Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

Ion pathways in the taste bud and their significance for transduction.

PubMed

DeSimone, J A; Ye, Q; Heck, G L

1993-01-01

Taste buds share a topology with ion-transporting epithelial and evidence now indicates that neural responses in rats to Na+ salts of differing anion are mediated by both transcellular and paracellular ion transport. Na+ exerts its effects mainly on the transcellular pathway. Neural responses to Na+ salts are enhanced by negative voltage clamp and suppressed by positive clamp in a manner indicating modulation of the apical membrane potential of receptor cells. Anion effects are mainly paracellular. Under zero current clamp increasing anion size reduces the neural response at constant Na+ concentration. Below about 50 mM this difference is entirely eliminated under voltage clamp. This suggests that paracellular transepithelial potentials normally create an anion difference. At higher concentrations the relatively high permeability of the paracellular shunt to Cl- permits sufficient electroneutral diffusion of NaCl below the tight junctions to stimulate cells that do not make direct contact with the oral cavity. In general, the sensitivity of a response to perturbations in the apical membrane potential indicates that some phase of Na+ salt taste transduction is accompanied by changes in an apical membrane channel conductance.

Synchrotron-based transmission x-ray microscopy for improved extraction in shale during hydraulic fracturing

NASA Astrophysics Data System (ADS)

Kiss, Andrew M.; Jew, Adam D.; Joe-Wong, Claresta; Maher, Kate M.; Liu, Yijin; Brown, Gordon E.; Bargar, John

2015-09-01

Engineering topics which span a range of length and time scales present a unique challenge to researchers. Hydraulic fracturing (fracking) of oil shales is one of these challenges and provides an opportunity to use multiple research tools to thoroughly investigate a topic. Currently, the extraction efficiency from the shale is low but can be improved by carefully studying the processes at the micro- and nano-scale. Fracking fluid induces chemical changes in the shale which can have significant effects on the microstructure morphology, permeability, and chemical composition. These phenomena occur at different length and time scales which require different instrumentation to properly study. Using synchrotron-based techniques such as fluorescence tomography provide high sensitivity elemental mapping and an in situ micro-tomography system records morphological changes with time. In addition, the transmission X-ray microscope (TXM) at the Stanford Synchrotron Radiation Lightsource (SSRL) beamline 6-2 is utilized to collect a nano-scale three-dimensional representation of the sample morphology with elemental and chemical sensitivity. We present the study of a simplified model system, in which pyrite and quartz particles are mixed and exposed to oxidizing solution, to establish the basic understanding of the more complex geology-relevant oxidation reaction. The spatial distribution of the production of the oxidation reaction, ferrihydrite, is retrieved via full-field XANES tomography showing the reaction pathway. Further correlation between the high resolution TXM data and the high sensitivity micro-probe data provides insight into potential morphology changes which can decrease permeability and limit hydrocarbon recovery.

Characterizing flow pathways in a sandstone aquifer at multiple depths

NASA Astrophysics Data System (ADS)

Medici, Giacomo; West, Jared; Mountney, Nigel

2017-04-01

Sandstone aquifers are commonly assumed to represent porous media characterized by a permeable matrix. However, such aquifers may be heavily fractured where rock properties and timing of deformation favour brittle failure and crack opening. In many aquifer types, fractures associated with faults, bedding planes and stratabound joints represent preferential pathways for fluids and contaminants. This presentation reports well-test results and outcrop-scale studies that reveal how strongly lithified siliciclastic rocks may be entirely dominated by fracture flow at shallow depths (≤ 150 m), similar to limestone and crystalline aquifers. The Triassic St Bees Sandstone Formation of the UK East Irish Sea Basin represents an optimum succession for study of the influence of both sedimentary and tectonic aquifer heterogeneities in a strongly lithified sandstone aquifer-type. This sedimentary succession of fluvial origin accumulated in rapidly subsiding basins, which typically favour preservation of complete depositional cycles, including fine-grained mudstone and silty sandstone layers of floodplain origin interbedded with sandstone-dominated fluvial channel deposits. Vertical joints in the St Bees Sandstone Formation form a pervasive stratabound system whereby joints terminate at bedding-parallel discontinuities. Additionally, normal faults are present through the succession and record development of open-fractures in their damage zones. Here, the shallow aquifer (depth ≤150 m BGL) was characterized in outcrop and well tests. Fluid temperature, conductivity and flow-velocity logs record inflows and outflows from normal faults, as well as from pervasive bed-parallel fractures. Quantitative flow logging analyses in boreholes that cut fault planes indicate that zones of fault-related open fractures typically represent ˜ 50% of well transmissivity. The remaining flow component is dominated by bed-parallel fractures. However, such sub-horizontal fractures become the principal flow conduits in wells that penetrate the exterior parts of fault damage zones, as well as in non-faulted areas. Optical televiewer logs show development of karst-like conduits in correspondence of bedding fractures and faults up to 150 m below the ground surface, where recharge water containing dissolved carbonic acid enlarges fractures; these features may be responsible for the relatively high field-scale permeability (K˜0.1-1 m/day) of the phreatic zone at these depths. Below this 'karstifed' zone, field-scale permeability progressively decreases from K˜10-2 to 10-4 m/day from 150 m to 1100 m depth. Notably, differences between plug and field-scale permeability, and frequency of well in-flows seen in temperature and conductivity logs, also decrease between intermediate (150 to 450 m) and elevated (450 to 1100 m) depths. This confirms how fracture closure leads to a progressively more important matrix contribution to flow with increasing lithostatic stress, leading to intergranular flow dominance at ˜ 1 km depth.

Flow zone characterisation in a fractured aquifer using spring and open-well T and EC monitoring.

NASA Astrophysics Data System (ADS)

Agbotui, Prodeo; West, Landis; Bottrell, Simon

2017-04-01

The Cretaceous Chalk is a very important aquifer in England, and its relatively high transmissivity derives essentially from a well-developed network of solutionally-enhanced fractures and conduits. Like other fractured aquifers, characterisation and delineation of flow pathways and hence catchment boundaries is important. Determination of flow pathways for source catchment delineation (e.g. identification of safeguarding zones around wells) is critical for the effective management and protection of the groundwater resource. It also determines the areal extent of contamination from known sources, and enables the targeted sampling of flow zones e.g. for monitored natural attenuation (MNA). A rather simplistic conceptualisation of the unconfined chalk aquifer of East Yorkshire is currently used as a basis for numerical simulations: linearly reducing hydraulic conductivity (K) with depth below the maximum groundwater elevation, reducing to a minimum value below the zone of groundwater table fluctuation. This study represents an attempt to improve this conceptualisation via improved characterisation of permeable zones within the aquifer. The methods used are: pumping test drawdown analyses for transmissivity, ambient open-well dilution testing; rainfall, groundwater head, and spring / open-well specific electrical conductance (SEC) and temperature monitoring. Pumping test analyses yield overall well transmissivity; the open-well dilution/monitoring approach identifies inflow, outflow, crossflow zones and direction and rate of flow in wells; seasonal changes in flows in wells and springs reflect the annual recharge and recession cycle and the impact of seasonal hydraulic head variation on the activation/deactivation of permeable pathways. Variations in spring and well-water electrical conductivity / temperature provide insight into groundwater residence times and the degree of isolation of groundwater from atmospheric and soil zone sources of CO2. The results of the study combined with stratigraphic information on the aquifer, allows the characterisation of the development of bedding-controlled features such as solutionally-enhanced fractures or conduits, and the role of steeply inclined normal faults. The results have implications for catchment management because it will inform a refinement and improvement of the regulatory body) groundwater model for assessment, evaluation and protection of groundwater resource. The method and techniques used can be applicable for characterising fractured aquifers in other jurisdictions.

Injection of Emulsified Vegetable Oil for Long-Term Bioreduction of Uranium

NASA Astrophysics Data System (ADS)

Brooks, S. C.; Watson, D. B.; Schadt, C. W.; Jardine, P. M.; Gihring, T. M.; Zhang, G.; Mehlhorn, T.; Lowe, K.; Phillips, J.; Earles, J.; Wu, W.; Criddle, C. S.; Kemner, K. M.; Boyanov, M.

2011-12-01

In situ bioremediation of a uranium and nitrate-contaminated aquifer with the slow-release electron donor, emulsified vegetable oil (EVO), was tested at the US DOE Subsurface Biogeochemical Research Program (SBR) Integrated Field Research Challenge (IFRC) site, in Oak Ridge, TN. The EVO injection took place in Area 2 of the IFRC located about 300 m downgradient of the former S-3 disposal ponds. Liquid wastes, disposed in the ponds from 1951 to 1983, were primarily composed of nitric acid, plating wastes containing various metals (Cr, Ni) radionuclides (U, Tc), inorganics (nitrate, sulfate) and organic contaminants (tetrachloroethylene, acetone). Prior pond closure in 1987, large volumes of waste fluids migrated into the subsurface, down Bear Creek Valley and into Bear Creek. Contaminants detected at Area 2 were transported through a high permeability gravelly fill that is considered a preferred transport pathway for U to Bear Creek. Groundwater in the gravelly fill is contaminated with U (1-3 mg/L), sulfate (95-130 mg/L), and nitrate (20-40 mg/L) and 500 mg/kg or higher U has been detected on the solid phase of the fill material. The objective of this study is to investigate the feasibility and long-term sustainability of U(VI) reduction and immobilization, and nitrate degradation in the high permeability, high flow gravel fill using EVO as the electron donor. A one-time EVO injection was conducted over a 2 hour period in the highly permeable gravel (hydraulic conductivity 0.08 cm/sec) in the well instrumented IFRC Area 2 field plot. Extensive monitoring of geochemical parameters, dissolved gases and microbial populations were conducted during the test. A bromide tracer test was conducted prior to the injection of the EVO to assess transport pathways and rates. Geochemical analysis of site groundwater demonstrated the sequential bioreduction of oxygen, nitrate, Mn(IV), Fe(III) and sulfate. Transient accumulation of acetate was observed as an intermediate in the oil degradation. Reduction and removal of U and nitrate from groundwater was observed in all wells in hydraulic connection to the injection wells after 2-4 weeks. U concentrations in groundwater were reduced to below 30 ppb (US EPA drinking water standard) at some well locations and nitrate was reduced to below detectable levels. Rebound of U in groundwater was observed together with the rebound of sulfate concentrations as the EVO was consumed. The flux of U and nitrate contamination from groundwater to the surface water receptor (Bear Creek) was significantly reduced by the EVO injection over a one year period. Uranium (VI) reduction to U(IV) in the field tests was confirmed by X-ray absorption near-edge spectroscopy (XANES) analysis. The reduced U(IV) was determined by X-ray absorption fine structure (XAFS) to be in an Fe-U complex, not uraninite. The activities of major Fe(III)- and sulfate-reducing bacteria with U(VI)-reducing capability as well as methanogens was stimulated after injection of the oil.

Fracture distribution and porosity in a fault-bound hydrothermal system (Grimsel Pass, Swiss Alps)

NASA Astrophysics Data System (ADS)

Egli, Daniel; Küng, Sulamith; Baumann, Rahel; Berger, Alfons; Baron, Ludovic; Herwegh, Marco

2017-04-01

The spatial distribution, orientation and continuity of brittle and ductile structures strongly control fluid pathways in a rock mass by joining existing pores and creating new pore space (fractures, joints) but can also act as seals to fluid flow (e.g. ductile shear zones, clay-rich fault gouges). In long-lived hydrothermal systems, permeability and the related fluid flow paths are therefore dynamic in space and time. Understanding the evolution and behaviour of naturally porous and permeable rock masses is critical for the successful exploration and sustainable exploitation of hydrothermal systems and can advance methods for planning and implementation of enhanced geothermal systems. This study focuses on an active fault-bound hydrothermal system in the crystalline basement of the Aar Massif (hydrothermal field Grimsel Pass, Swiss Alps) that has been exhumed from few kilometres depth and which documents at least 3 Ma of hydrothermal activity. The explored rock unit of the Aar massif is part of the External Crystalline Massifs that hosts a multitude of thermal springs on its southern border in the Swiss Rhône valley and furthermore represents the exhumed equivalent of potentially exploitable geothermal reservoirs in the deep crystalline subsurface of the northern Alpine foreland basin. This study combines structural data collected from a 125 m long drillhole across the hydrothermal zone, the corresponding drill core and surface mapping. Different methods are applied to estimate the porosity and the structural evolution with regard to porosity, permeability and fracture distribution. Analyses are carried out from the micrometre to decametre scale with main focus on the flow path evolution with time. This includes a large variety of porosity-types including fracture-porosity with up to cm-sized aperture down to grain-scale porosity. Main rock types are granitoid host rocks, mylonites, paleo-breccia and recent breccias. The porosity of the host rock as well as the cemented paleo-hydrothermal breccia is typically very low with values <1%. The high volume of mineralized fractures in the paleo-breccia indicates high porosity in former times, which is today closed by newly developed cements. The preservation of such paleo-breccias allow the investigation of contrasts between the fossil porosity/permeability and the present day active flow path, which is defined by fracture porosity that generally follows the regional deformation pattern and forms a wide network of interconnected fractures of variable orientation.

Microwave permeability of stripe patterned FeCoN thin film

NASA Astrophysics Data System (ADS)

Wu, Yuping; Yang, Yong; Ma, Fusheng; Zong, Baoyu; Yang, Zhihong; Ding, Jun

2017-03-01

Magnetic stripe patterns are of great importance for microwave applications owing to their highly tunable microwave permeability by adjusting the geometrical dimensions. In this work, stripe patterned FeCoN films with 160 nm thickness are fabricated by using standard UV photolithography. Their microwave permeability are investigated systematically via both experiment and micromagnetic simulation. The good agreement between experimental and simulation results suggests that stripe width is crucial for the microwave magnetic properties of the stripe pattern. It is demonstrated by simulation that with increasing stripe width from 1 to 80 μm the initial permeability shows a continuous growth from about 8-322, whiles the resonance frequency drops dramatically from 18.7 to 3.1 GHz at 4 μm gap size. Smaller gap size would result in slightly increased initial permeability due to larger magnetic volume ratio, accompanied by decreased resonance frequency because of stronger magnetostatic interaction. Moreover, the experimental investigation on stripe length effect indicates that the stripe length should be kept as long as possible to achieve uniform bulk resonance mode and high permeability value. Insufficient stripe length would result in low frequency edge mode and decayed bulk mode. This study could provide valuable guidelines on the selection of proper geometry dimensions of FeCoN stripe patterns for high frequency applications.

Bioinspired Layer-by-Layer Microcapsules Based on Cellulose Nanofibers with Switchable Permeability.

PubMed

Paulraj, Thomas; Riazanova, Anastasia V; Yao, Kun; Andersson, Richard L; Müllertz, Anette; Svagan, Anna J

2017-04-10

Green, all-polysaccharide based microcapsules with mechanically robust capsule walls and fast, stimuli-triggered, and switchable permeability behavior show great promise in applications based on selective and timed permeability. Taking a cue from nature, the build-up and composition of plant primary cell walls inspired the capsule wall assembly, because the primary cell walls in plants exhibit high mechanical properties despite being in a highly hydrated state, primarily owing to cellulose microfibrils. The microcapsules (16 ± 4 μm in diameter) were fabricated using the layer-by-layer technique on sacrificial CaCO 3 templates, using plant polysaccharides (pectin, cellulose nanofibers, and xyloglucan) only. In water, the capsule wall was permeable to labeled dextrans with a hydrodynamic diameter of ∼6.6 nm. Upon exposure to NaCl, the porosity of the capsule wall quickly changed allowing larger molecules (∼12 nm) to permeate. However, the porosity could be restored to its original state by removal of NaCl, by which permeants became trapped inside the capsule's core. The high integrity of cell wall was due to the CNF and the ON/OFF alteration of the permeability properties, and subsequent loading/unloading of molecules, could be repeated several times with the same capsule demonstrating a robust microcontainer with controllable permeability properties.

Monodisperse CNT Microspheres for High Permeability and Efficiency Flow-Through Filtration Applications.

PubMed

Copic, Davor; Maggini, Laura; De Volder, Michael

2018-03-01

Carbon nanotube (CNT)-based filters have the potential to revolutionize water treatment because of their high capacity and fast kinetics in sorption of organic, inorganic, and biological pollutants. To date, CNT filters either rely on CNTs dispersed in liquids, which are difficult to recover and cause safety concerns, or on CNT buckypaper, which offers high efficiency, but suffers from an intrinsic trade-off between filter permeability and capacity. Here, a new approach is presented that bypasses this trade-off and achieves buckypaper-like efficiency combined with filter-column-like permeability and capacity. For this, CNTs are first assembled into porous microspheres and then are packed into microfluidic column filters. These microcolumns exhibit large flow-through filtration efficiencies, while maintaining membrane permeabilities an order of magnitude larger then CNT buckypaper and specific permeabilities double that of activated carbon for similar flowrates (232 000 L m -2 h -1 bar -1 , 1.23 × 10 -12 m 2 ). Moreover, in a test to remove sodium dodecyl sulfate (SDS) from water, these microstructured CNT columns outperform activated carbon columns. This improved filtration efficiency and permeability is an important step toward a broader implementation of CNT-based filtration devices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of Pore-Lining Residues in Defining the Rate of Water Conduction by Aquaporin-0.

PubMed

Saboe, Patrick O; Rapisarda, Chiara; Kaptan, Shreyas; Hsiao, Yu-Shan; Summers, Samantha R; De Zorzi, Rita; Dukovski, Danijela; Yu, Jiaheng; de Groot, Bert L; Kumar, Manish; Walz, Thomas

2017-03-14

Compared to other aquaporins (AQPs), lens-specific AQP0 is a poor water channel, and its permeability was reported to be pH-dependent. To date, most water conduction studies on AQP0 were performed on protein expressed in Xenopus oocytes, and the results may therefore also reflect effects introduced by the oocytes themselves. Experiments with purified AQP0 reconstituted into liposomes are challenging because the water permeability of AQP0 is only slightly higher than that of pure lipid bilayers. By reconstituting high amounts of AQP0 and using high concentrations of cholesterol to reduce the permeability of the lipid bilayer, we improved the signal-to-noise ratio of water permeability measurements on AQP0 proteoliposomes. Our measurements show that mutation of two pore-lining tyrosine residues, Tyr-23 and Tyr-149 in sheep AQP0, to the corresponding residues in the high-permeability water channel AQP1 have additive effects and together increase the water permeability of AQP0 40-fold to a level comparable to that of AQP1. Molecular dynamics simulations qualitatively support these experimental findings and suggest that mutation of Tyr-23 changes the pore profile at the gate formed by residue Arg-187. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Resin Film Infusion (RFI) Process Modeling for Large Transport Aircraft Wing Structures

NASA Technical Reports Server (NTRS)

Knott, Tamara W.; Loos, Alfred C.

2000-01-01

Resin film infusion (RFI) is a cost-effective method for fabricating stiffened aircraft wing structures. The RFI process lends itself to the use of near net shape textile preforms manufactured through a variety of automated textile processes such as knitting and braiding. Often, these advanced fiber architecture preforms have through-the-thickness stitching for improved damage tolerance and delamination resistance. The challenge presently facing RFI is to refine the process to ensure complete infiltration and cure of a geometrically complex shape preform with the high fiber volume fraction needed for structural applications. An accurate measurement of preform permeability is critical for successful modeling of the RFI resin infiltration process. Small changes in the permeability can result in very different infiltration behavior and times. Therefore, it is important to accurately measure the permeabilities of the textile preforms used in the RFI process. The objective of this investigation was to develop test methods that can be used to measure the compaction behavior and permeabilities of high fiber volume fraction, advanced fiber architecture textile preforms. These preforms are often highly compacted due to through-the-thickness stitching used to improve damage tolerance. Test fixtures were designed and fabricated and used to measure both transverse and in-plane permeabilities. The fixtures were used to measure the permeabilities of multiaxial warp knit and triaxial braided preforms at fiber volume fractions from 55% to 65%. In addition, the effects of stitching characteristics, thickness, and batch variability on permeability and compaction behavior were investigated.

Molecular basis of usher pore gating in Escherichia coli pilus biogenesis.

PubMed

Volkan, Ender; Kalas, Vasilios; Pinkner, Jerome S; Dodson, Karen W; Henderson, Nadine S; Pham, Thieng; Waksman, Gabriel; Delcour, Anne H; Thanassi, David G; Hultgren, Scott J

2013-12-17

Extracellular fibers called chaperone-usher pathway pili are critical virulence factors in a wide range of Gram-negative pathogenic bacteria that facilitate binding and invasion into host tissues and mediate biofilm formation. Chaperone-usher pathway ushers, which catalyze pilus assembly, contain five functional domains: a 24-stranded transmembrane β-barrel translocation domain (TD), a β-sandwich plug domain (PLUG), an N-terminal periplasmic domain, and two C-terminal periplasmic domains (CTD1 and 2). Pore gating occurs by a mechanism whereby the PLUG resides stably within the TD pore when the usher is inactive and then upon activation is translocated into the periplasmic space, where it functions in pilus assembly. Using antibiotic sensitivity and electrophysiology experiments, a single salt bridge was shown to function in maintaining the PLUG in the TD channel of the P pilus usher PapC, and a loop between the 12th and 13th beta strands of the TD (β12-13 loop) was found to facilitate pore opening. Mutation of the β12-13 loop resulted in a closed PapC pore, which was unable to efficiently mediate pilus assembly. Deletion of the PapH terminator/anchor resulted in increased OM permeability, suggesting a role for the proper anchoring of pili in retaining OM integrity. Further, we introduced cysteine residues in the PLUG and N-terminal periplasmic domains that resulted in a FimD usher with a greater propensity to exist in an open conformation, resulting in increased OM permeability but no loss in type 1 pilus assembly. These studies provide insights into the molecular basis of usher pore gating and its roles in pilus biogenesis and OM permeability.

Quantitative imaging of intracellular signaling for personalized pancreatic cancer therapy in an in vivo avatar (Conference Presentation)

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Schultz, Emily; Park, Yeonjae; Fischer, Dawn; Pogue, Brian W.; Smith, Kerrington; Tichauer, Kenneth M.; Gibbs, Summer L.

2017-02-01

Pancreatic ductal adenocarcinomas (PDAC) are notoriously difficult to treat and in general, molecular targeted therapies have failed even when the targeted protein is overexpressed in the tumor tissue. Genetic mutations in extracellular receptors and downstream signaling proteins (i.e., RAS signaling pathway) and convoluted intracellular cross-talk between cell signaling pathways are likely reasons that these promising therapies fail. Monitoring the complex relationship between intracellular protein signaling is difficult and to-date, standard techniques that are used (Western blot, flow cytometry, immunohistochemistry, etc.) are invasive, static and do not accurately represent in vivo structure-function relationships. Here, we describe the development of an in ovo avatar using patient derived tumors grown on the chicken chorioallantoic membrane (CAM) and the novel fluorescence-based Quantitative Protein Expression Tracking (QUIET) methodology to bridge the gap between oncology, genomics and patient outcomes. Previously developed paired-agent imaging, was extended to a three-compartment model system in QUIET, which utilizes three types of imaging agents: novel fluorophore conjugated cell permeable targeted and untargeted small molecule paired-agents, in addition to a tumor perfusion agent that is not cell membrane permeable. We have demonstrated the ability to quantify the intracellular binding domain of a trans-membrane protein in vitro using cell permeable fluorescent agents (erlotinib-TRITC and control isotype-BODIPY FL). In addition, we have demonstrated imaging protocols to simultaneously image up to 6 spectrally distinct organic fluorophores in in ovo avatars using the Nuance EX (Perkin Elmer) and established proof-of-principle intracellular and extracellular protein concentrations of epidermal growth factor receptor using QUIET and traditional paired-agent imaging.

Calcium-permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors Trigger Neuronal Nitric-oxide Synthase Activation to Promote Nerve Cell Death in an Src Kinase-dependent Fashion*

PubMed Central

Socodato, Renato; Santiago, Felipe N.; Portugal, Camila C.; Domingues, Ana F.; Santiago, Ana R.; Relvas, João B.; Ambrósio, António F.; Paes-de-Carvalho, Roberto

2012-01-01

In the retina information decoding is dependent on excitatory neurotransmission and is critically modulated by AMPA glutamate receptors. The Src-tyrosine kinase has been implicated in modulating neurotransmission in CNS. Thus, our main goal was to correlate AMPA-mediated excitatory neurotransmission with the modulation of Src activity in retinal neurons. Cultured retinal cells were used to access the effects of AMPA stimulation on nitric oxide (NO) production and Src phosphorylation. 4-Amino-5-methylamino-2′,7′-difluorofluorescein diacetate fluorescence mainly determined NO production, and immunocytochemistry and Western blotting evaluated Src activation. AMPA receptors activation rapidly up-regulated Src phosphorylation at tyrosine 416 (stimulatory site) and down-regulated phosphotyrosine 527 (inhibitory site) in retinal cells, an effect mainly mediated by calcium-permeable AMPA receptors. Interestingly, experiments confirmed that neuronal NOS was activated in response to calcium-permeable AMPA receptor stimulation. Moreover, data suggest NO pathway as a key regulatory signaling in AMPA-induced Src activation in neurons but not in glial cells. The NO donor SNAP (S-nitroso-N-acetyl-dl-penicillamine) and a soluble guanylyl cyclase agonist (YC-1) mimicked AMPA effect in Src Tyr-416 phosphorylation, reinforcing that Src activation is indeed modulated by the NO pathway. Gain and loss-of-function data demonstrated that ERK is a downstream target of AMPA-induced Src activation and NO signaling. Furthermore, AMPA stimulated NO production in organotypic retinal cultures and increased Src activity in the in vivo retina. Additionally, AMPA-induced apoptotic retinal cell death was regulated by both NOS and Src activity. Because Src activity is pivotal in several CNS regions, the data presented herein highlight that Src modulation is a critical step in excitatory retinal cell death. PMID:22992730

Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

PubMed

Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

2018-01-15

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

Calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors trigger neuronal nitric-oxide synthase activation to promote nerve cell death in an Src kinase-dependent fashion.

PubMed

Socodato, Renato; Santiago, Felipe N; Portugal, Camila C; Domingues, Ana F; Santiago, Ana R; Relvas, João B; Ambrósio, António F; Paes-de-Carvalho, Roberto

2012-11-09

In the retina information decoding is dependent on excitatory neurotransmission and is critically modulated by AMPA glutamate receptors. The Src-tyrosine kinase has been implicated in modulating neurotransmission in CNS. Thus, our main goal was to correlate AMPA-mediated excitatory neurotransmission with the modulation of Src activity in retinal neurons. Cultured retinal cells were used to access the effects of AMPA stimulation on nitric oxide (NO) production and Src phosphorylation. 4-Amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence mainly determined NO production, and immunocytochemistry and Western blotting evaluated Src activation. AMPA receptors activation rapidly up-regulated Src phosphorylation at tyrosine 416 (stimulatory site) and down-regulated phosphotyrosine 527 (inhibitory site) in retinal cells, an effect mainly mediated by calcium-permeable AMPA receptors. Interestingly, experiments confirmed that neuronal NOS was activated in response to calcium-permeable AMPA receptor stimulation. Moreover, data suggest NO pathway as a key regulatory signaling in AMPA-induced Src activation in neurons but not in glial cells. The NO donor SNAP (S-nitroso-N-acetyl-DL-penicillamine) and a soluble guanylyl cyclase agonist (YC-1) mimicked AMPA effect in Src Tyr-416 phosphorylation, reinforcing that Src activation is indeed modulated by the NO pathway. Gain and loss-of-function data demonstrated that ERK is a downstream target of AMPA-induced Src activation and NO signaling. Furthermore, AMPA stimulated NO production in organotypic retinal cultures and increased Src activity in the in vivo retina. Additionally, AMPA-induced apoptotic retinal cell death was regulated by both NOS and Src activity. Because Src activity is pivotal in several CNS regions, the data presented herein highlight that Src modulation is a critical step in excitatory retinal cell death.

A three-pathway pore model describes extensive transport data from Mammalian microvascular beds and frog microvessels.

PubMed

Wolf, Matthew B

2002-12-01

To show that a three-pathway pore model can describe extensive transport data in cat and rat skeletal muscle microvascular beds and in frog mesenteric microvessels. A three-pathway pore model was used to predict transport data measured in various microcirculatory preparations. The pathways consist of 4- and 24-nm radii pore systems with a 2.5:1 ratio of hydraulic conductivities and a water-only pathway of variable conductivity. The pore sizes and relative hydraulic conductivities of the small- and large-pore systems were derived from a model fit to reflection coefficient (sigma) data in the cat hindlimb. The fraction (alpha(w)) of total hydraulic conductivity (L(p)) or hydraulic capacity (L(p)S) contributed by the water-only pathway was uniquely determined for each preparation by a fit of the three-pathway model (parameters fixed as above) to sigma data measured in that preparation. These parameter values were unchanged when the model was used to predict diffusion capacity (permeability-surface area product, P(d)S) data in the cat or rat preparations or diffusional permeability (P(d)) data in frog microvessels. The values for L(p) or L(p)S used to predict diffusional data in each preparation were taken from the literature. Predictions of P(d) ratios for solute pairs were also compared with experimental data. The three-pathway model closely predicted the trend of P(d)S or P(d) experimental data in all three preparations; in general, predicted P(d) ratios for paired solutes were quite similar to experimental data. For these comparisons, the only parameter varied between these preparations was alpha(w). It varied considerably, from 7 to 16 to 41% of total in frog, rat, and cat preparations. Individual P(d)S or P(d) experimental data were closely predicted in the cat but somewhat overestimated in the frog and rat. This result could be due the use of L(p) or L(p)S values in the model that were affected by methodological problems. Calculated hydraulic conductivities of the water-only pathway in the three preparations were quite similar. : These results support the hypothesis of a common structure of the transmembrane pathways in these three, very different, microcirculatory preparations. What varies considerably between them is the total number of solute-conducting pathways, but not their dimensions, nor the hydraulic conductivities of their water-only pathways. Because of the wide variation of alpha(w) among these preparations, the ratio of P(d) to L(p) for any solute is not constant, but the deviation from constancy may not be detectable because of errors in the experimental data.

Influence of Normal and Shear Stress on the Hydraulic Transmissivity of Thin Cracks in a Tight Quartz Sandstone, a Granite, and a Shale

NASA Astrophysics Data System (ADS)

Rutter, Ernest H.; Mecklenburgh, Julian

2018-02-01

Transmissivity of fluids along fractures in rocks is reduced by increasing normal stress acting across them, demonstrated here through gas flow experiments on Bowland shale, and oil flow experiments on Pennant sandstone and Westerly granite. Additionally, the effect of imposing shear stress at constant normal stress was determined, until frictional sliding started. In all cases, increasing shear stress causes an accelerating reduction of transmissivity by 1 to 3 orders of magnitude as slip initiated, as a result of the formation of wear products that block fluid pathways. Only in the case of granite, and to a lesser extent in the sandstone, was there a minor amount of initial increase of transmissivity prior to the onset of slip. These results cast into doubt the commonly applied presumption that cracks with high resolved shear stresses are the most conductive. In the shale, crack transmissivity is commensurate with matrix permeability, such that shales are expected always to be good seals. For the sandstone and granite, unsheared crack transmissivity was respectively 2 and 2.5 orders of magnitude greater than matrix permeability. For these rocks crack transmissivity can dominate fluid flow in the upper crust, potentially enough to permit maintenance of a hydrostatic fluid pressure gradient in a normal (extensional) faulting regime.

Development of practical red fluorescent probe for cytoplasmic calcium ions with greatly improved cell-membrane permeability.

PubMed

Hirabayashi, Kazuhisa; Hanaoka, Kenjiro; Egawa, Takahiro; Kobayashi, Chiaki; Takahashi, Shodai; Komatsu, Toru; Ueno, Tasuku; Terai, Takuya; Ikegaya, Yuji; Nagano, Tetsuo; Urano, Yasuteru

2016-10-01

Fluorescence imaging of calcium ions (Ca(2+)) has become an essential technique for investigation of signaling pathways involving Ca(2+) as a second messenger. But, Ca(2+) signaling is involved in many biological phenomena, and therefore simultaneous visualization of Ca(2+) and other biomolecules (multicolor imaging) would be particularly informative. For this purpose, we set out to develop a fluorescent probe for Ca(2+) that would operate in a different color region (red) from that of probes for other molecules, many of which show green fluorescence, as exemplified by green fluorescent protein (GFP). We previously developed a red fluorescent probe for monitoring cytoplasmic Ca(2+) concentration, based on our established red fluorophore, TokyoMagenta (TM), but there remained room for improvement, especially as regards efficiency of introduction into cells. We considered that this issue was probably mainly due to limited water solubility of the probe. So, we designed and synthesized a red-fluorescent probe with improved water solubility. We confirmed that this Ca(2+) red-fluorescent probe showed high cell-membrane permeability with bright fluorescence. It was successfully applied to fluorescence imaging of not only live cells, but also brain slices, and should be practically useful for multicolor imaging studies of biological mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aminopurvalanol A, a Potent, Selective, and Cell Permeable Inhibitor of Cyclins/Cdk Complexes, Causes the Reduction of in Vitro Fertilizing Ability of Boar Spermatozoa, by Negatively Affecting the Capacitation-Dependent Actin Polymerization

PubMed Central

Bernabò, Nicola; Valbonetti, Luca; Greco, Luana; Capacchietti, Giulia; Ramal Sanchez, Marina; Palestini, Paola; Botto, Laura; Mattioli, Mauro; Barboni, Barbara

2017-01-01

The adoption of high-througput technologies demonstrated that in mature spermatozoa are present proteins that are thought to be not present or active in sperm cells, such as those involved in control of cell cycle. Here, by using an in silico approach based on the application of networks theory, we found that Cyclins/Cdk complexes could play a central role in signal transduction active during capacitation. Then, we tested this hypothesis in the vitro model. With this approach, spermatozoa were incubated under capacitating conditions in control conditions (CTRL) or in the presence of Aminopurvalanol A a potent, selective and cell permeable inhibitor of Cyclins/Cdk complexes at different concentrations (2, 10, and 20 μM). We found that this treatment caused dose-dependent inhibition of sperm fertilizing ability. We attribute this event to the loss of acrosome integrity due to the inhibition of physiological capacitation-dependent actin polymerization, rather than to a detrimental effect on membrane lipid remodeling or on other signaling pathways such as tubulin reorganization or MAPKs activation. In our opinion, these data could revamp the knowledge on biochemistry of sperm capacitation and could suggest new perspectives in studying male infertility. PMID:29312003

Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability.

PubMed

Lew, V L; Ortiz, O E; Bookchin, R M

1997-06-01

To explore basic properties of the sickling-induced cation permeability pathway, the Ca2+ component (Psickle-Ca) was studied in density-fractionated sickle cell anemia (SS) discocytes through its effects on the activity of the cells' Ca2+sensitive K+-channels (KCa). The instant state of KCa channel activation was monitored during continuous or cyclic deoxygenation of the cells using a novel thiocyanate-densecell formation method. Each deoxy pulse caused a reversible, sustained Psickle-Ca, which activated KCa channels in only 10-45% of cells at physiological [Ca2+]o ("activated cells"). After removal of cells activated by each previous deoxy pulse, subsequent pulses generated similar activated cell fractions, indicating a random determination rather than the response of a specific vulnerable subpopulation. The fraction of activated cells rose monotonically with [Ca2+]o along a curve reflecting the cells' distribution of Psickle-Ca, with values high enough in a small cell fraction to trigger near-maximal KCa channels. Consistent with the stochastic nature of Psickle-Ca, repeated deoxygenated-oxygenated pulsing led to progressive dense cell formation, whereas single long pulses caused one early density shift. Thus deoxygenation-induced Ca2+-permeabilization in SS cells is a probabilistic event with large cumulative dehydrating potential. The possible molecular nature of Psickle-Ca is discussed.

Preliminary Test Results of Heshe Hydrogeological Experimental Well Station in Taiwan

NASA Astrophysics Data System (ADS)

Chuang, P.; Liu, C.; Lin, M.; Chan, W.; Lee, T.; Chia, Y.; Teng, M.; Liu, C.

2013-12-01

Safe disposal of radioactive waste is a critical issue for the development of nuclear energy. The design of final disposal system is based on the concept of multiple barriers which integrate the natural barriers and engineering barriers for long-term isolation of radioactive wastes. As groundwater is the major medium that can transport radionuclides to our living environment, it is essential to characterize groundwater flow at the disposal site. Taiwan is located at the boundary between the Eurasian plate and the Philippine Sea plate. Geologic formations are often fractured due to tectonic compression and extension. In this study, a well station for the research and development of hydrogeological techniques was established at the Experimental Forest of the National Taiwan University in central Taiwan. There are 10 testing wells, ranging in depth from 25 m to 100 m, at the station. The bedrock beneath the regolith is highly fractured mudstone. As fracture is the preferential pathway of the groundwater flow, the focus of in-situ tests is to investigate the location of permeable fractures and the connection of permeable fractures. Several field tests have been conducted, including geophysical logging, heat-pulse flowmeter, hydraulic test, tracer test and double packer test, for the development of advanced technologies to detect the preferential groundwater flow in fractured rocks.

Analytical solutions for flow fields near drain-and-gate reactive barriers.

PubMed

Klammler, Harald; Hatfield, Kirk; Kacimov, Anvar

2010-01-01

Permeable reactive barriers (PRBs) are a popular technology for passive contaminant remediation in aquifers through installation of reactive materials in the pathway of a plume. Of fundamental importance are the degree of remediation inside the reactor (residence time) and the portion of groundwater intercepted by a PRB (capture width). Based on a two-dimensional conformal mapping approach (previously used in related work), the latter is studied in the present work for drain-and-gate (DG) PRBs, which may possess a collector and a distributor drain ("full" configuration) or a collector drain only ("simple" configuration). Inherent assumptions are a homogeneous unbounded aquifer with a uniform far field, in which highly permeable drains establish constant head boundaries. Solutions for aquifer flow fields in terms of the complex potential are derived, illustrated, and analyzed for doubly symmetric DG configurations and arbitrary reactor hydraulic resistance as well as ambient groundwater flow direction. A series of practitioner-friendly charts for capture width is given to assist in PRB design and optimization without requiring complex mathematics. DG PRBs are identified as more susceptible to flow divergence around the reactor than configurations using impermeable side structures (e.g., funnel-and-gate), and deployment of impermeable walls on drains is seen to mitigate this problem under certain circumstances.

Direct push injection logging for high resolution characterization of low permeability zones

NASA Astrophysics Data System (ADS)

Liu, G.; Knobbe, S.; Butler, J. J., Jr.; Reboulet, E. C.; Borden, R. C.; Bohling, G.

2017-12-01

One of the grand challenges for groundwater protection and contaminated site remediation efforts is dealing with the slow, yet persistent, release of contaminants from low permeability zones. In zones of higher permeability, groundwater flow is relatively fast and contaminant transport can be more effectively affected by treatment activities. In the low permeability zones, however, groundwater flow and contaminant transport are slow and thus become largely insensitive to many in-situ treatment efforts. Clearly, for sites with low permeability zones, accurate depiction of the mass exchange between the low and higher permeability zones is critical for designing successful groundwater protection and remediation systems, which requires certain information such as the hydraulic conductivity (K) and porosity of the subsurface. The current generation of field methods is primarily developed for relatively permeable zones, and little work has been undertaken for characterizing zones of low permeability. For example, the direct push injection logging (DPIL) approach (e.g., Hydraulic Profiling Tool by Geoprobe) is commonly used for high resolution estimation of K over a range of 0.03 to 23 m/d. When K is below 0.03 m/d, the pressure responses from the current DPIL are generally too high for both the formation (potential formation alteration at high pressure) and measuring device (pressure exceeding the upper sensor limit). In this work, we modified the current DPIL tool by adding a low-flow pump and flowmeter so that injection logging can be performed with much reduced flow rates when K is low. Numerical simulations showed that the reduction in injection rates (reduced from 250 to 1 mL/min) allowed pressures to be measurable even when K was as low as 0.001 m/d. They also indicated that as the K decreased, the pore water pressure increase induced by probe advancement had a more significant impact on DPIL results. A new field DPIL profiling procedure was developed for reducing that impact. Our preliminary test results in both the lab and at a field site have demonstrated the promise of the modified DPIL approach as a practical method for characterizing low permeability zones.

Numerical Simulation of Hydraulic Fracturing in Low-/High-Permeability, Quasi-Brittle and Heterogeneous Rocks

NASA Astrophysics Data System (ADS)

Pakzad, R.; Wang, S. Y.; Sloan, S. W.

2018-04-01

In this study, an elastic-brittle-damage constitutive model was incorporated into the coupled fluid/solid analysis of ABAQUS to iteratively calculate the equilibrium effective stress of Biot's theory of consolidation. The Young's modulus, strength and permeability parameter of the material were randomly assigned to the representative volume elements of finite element models following the Weibull distribution function. The hydraulic conductivity of elements was associated with their hydrostatic effective stress and damage level. The steady-state permeability test results for sandstone specimens under different triaxial loading conditions were reproduced by employing the same set of material parameters in coupled transient flow/stress analyses of plane-strain models, thereby indicating the reliability of the numerical model. The influence of heterogeneity on the failure response and the absolute permeability was investigated, and the post-peak permeability was found to decrease with the heterogeneity level in the coupled analysis with transient flow. The proposed model was applied to the plane-strain simulation of the fluid pressurization of a cavity within a large-scale block under different conditions. Regardless of the heterogeneity level, the hydraulically driven fractures propagated perpendicular to the minimum principal far-field stress direction for high-permeability models under anisotropic far-field stress conditions. Scattered damage elements appeared in the models with higher degrees of heterogeneity. The partially saturated areas around propagating fractures were simulated by relating the saturation degree to the negative pore pressure in low-permeability blocks under high pressure. By replicating previously reported trends in the fracture initiation and breakdown pressure for different pressurization rates and hydraulic conductivities, the results showed that the proposed model for hydraulic fracture problems is reliable for a wide range of pressurization rates and permeability conditions.

Permeability structure and its influence on microbial activity at off-Shimokita basin, Japan

NASA Astrophysics Data System (ADS)

Tanikawa, W.; Yamada, Y.; Sanada, Y.; Kubo, Y.; Inagaki, F.

2016-12-01

The microbial populations and the limit of microbial life are probably limited by chemical, physical, and geological conditions, such as temperature, pore water chemistry, pH, and water activity; however, the key parameters affecting growth in deep subseafloor sediments remain unclarified (Hinrichs and Inagaki 2012). IODP expedition 337 was conducted near a continental margin basin off Shimokita Peninsula, Japan to investigate the microbial activity under deep marine coalbed sediments down to 2500 mbsf. Inagaki et al. (2015) discovered that microbial abundance decreased markedly with depth (the lowest cell density of <1 cell/cm3 was recorded below 2000 mbsf), and that the coal bed layers had relatively higher cell densities. In this study, permeability was measured on core samples from IODP Expedition 337 and Expedition CK06-06 in the D/V Chikyu shakedown cruise. Permeability was measured at in-situ effective pressure condition. Permeability was calculated by the steady state flow method by keeping differential pore pressure from 0.1 to 0.8 MPa.Our results show that the permeability for core samples decreases with depth from 10-16 m2 on the seafloor to 10-20 m2 at the bottom of hole. However, permeability is highly scattered within the coal bed unit (1900 to 2000 mbsf). Permeabilities for sandstone and coal is higher than those for siltstone and shale, therefore the scatter of the permeabilities at the same unit is due to the high variation of lithology. The highest permeability was observed in coal samples and this is probably due to formation of micro cracks (cleats). Permeability estimated from the NMR logging using the empirical parameters is around two orders of magnitude higher than permeability of core samples, even though the relative permeability variation at vertical direction is quite similar between core and logging data.The higher cell density is observed in the relatively permeable formation. On the other hand, the correlation between cell density, water activity, and porosity is not clear. On the assumption that pressure gradient is constant through the depth, flow rate can be proportional to permeability of sediments. Flow rate probably restricts the availability of energy and nutrient for microorganism, therefore permeability might have influenced on the microbial activity in the coalbed basin.

Determination of osthol and its metabolites in a phase I reaction system and the Caco-2 cell model by HPLC-UV and LC-MS/MS

PubMed Central

Yuan, Zhenting; Xu, Haiyan; Wang, Ke; Zhao, Zhonghua; Hu, Ming

2012-01-01

A straightforward and sensitive reversed-phase high-performance liquid chromatography (HPLC) assay was developed and validated for the analysis of osthol and its phase I metabolites (internal standard: umbelliferone). The method was validated for the determination of osthol with respect to selectivity, precision, linearity, limit of detection, recovery, and stability. The linear response range was 0.47 ~ 60 μM, and the average recoveries ranged from 98 to 101%. The inter-day and intra-day relative standard deviations were both less than 5%. Using this method, we showed that more than 80% of osthol was metabolized in 20 min in a phase I metabolic reaction system. Transport experiments in the Caco-2 cell culture model indicated that osthol was easily absorbed with high absorptive permeability (>10×10-6 cm/sec). The permeability did not display concentration-dependence or vectorial-dependence and is mildly temperature sensitive (activation energy less than 10 Kcal/mole), indicating passive mechanism of transport. When analyzed by LC-MS/MS, five metabolites were detected in a phase I reaction system and in the receiver side of a modified Caco-2 cell model, which was supplemented with the phase I reaction system. The major metabolites appeared to be desmethyl-osthol and multiple isomers of dehydro-osthol. In conclusion, a likely cause of poor osthol bioavailability is rapid phase I metabolism via the cytochrome P-450 pathways. PMID:19304430

Alveolar edema dispersion and alveolar protein permeability during high volume ventilation: effect of positive end-expiratory pressure.

PubMed

de Prost, Nicolas; Roux, Damien; Dreyfuss, Didier; Ricard, Jean-Damien; Le Guludec, Dominique; Saumon, Georges

2007-04-01

To evaluate whether PEEP affects intrapulmonary alveolar edema liquid movement and alveolar permeability to proteins during high volume ventilation. Experimental study in an animal research laboratory. 46 male Wistar rats. A (99m)Tc-labeled albumin solution was instilled in a distal airway to produce a zone of alveolar flooding. Conventional ventilation (CV) was applied for 30 min followed by various ventilation strategies for 3 h: CV, spontaneous breathing, and high volume ventilation with different PEEP levels (0, 6, and 8 cmH(2)O) and different tidal volumes. Dispersion of the instilled liquid and systemic leakage of (99m)Tc-albumin from the lungs were studied by scintigraphy. The instillation protocol produced a zone of alveolar flooding that stayed localized during CV or spontaneous breathing. High volume ventilation dispersed alveolar liquid in the lungs. This dispersion was prevented by PEEP even when tidal volume was the same and thus end-inspiratory pressure higher. High volume ventilation resulted in the leakage of instilled (99m)Tc-albumin from the lungs. This increase in alveolar albumin permeability was reduced by PEEP. Albumin permeability was more affected by the amplitude of tidal excursions than by overall lung distension. PEEP prevents the dispersion of alveolar edema liquid in the lungs and lessens the increase in alveolar albumin permeability due to high volume ventilation.

Hot and Steamy Fractures in the Philippines: The Geological Characterization and Permeability Evaluation of Fractures in the Southern Negros Geothermal Field, Philippines

NASA Astrophysics Data System (ADS)

Pastoriza, L. R.; Holdsworth, R.; McCaffrey, K. J. W.; Dempsey, E. D.; Walker, R. J.; Gluyas, J.; Reyes, J. K.

2016-12-01

Fluid flow pathway characterization is critical to geothermal exploration and exploitation. It requires a good understanding of the structural evolution, fault distribution and fluid flow properties. A dominantly fieldwork-based approach has been used to evaluate the potential fracture permeability characteristics of a typical high-temperature geothermal reservoir in the Southern Negros Geothermal Field, Philippines. This is a liquid-dominated geothermal resource hosted in the andesitic to dacitic Quaternary Cuernos de Negros Volcano in Negros Island. Fieldwork reveals two main fracture groups based on fault rock characteristics, alteration type, relative age of deformation, and associated thermal manifestation, with the younger fractures mainly related to the development of the modern geothermal system. Palaeostress analyses of cross-cutting fault and fracture arrays reveal a progressive counterclockwise rotation of stress axes from the (?)Pliocene up to the present-day, which is consistent with the regional tectonic models. A combined slip and dilation tendency analysis of the mapped faults indicates that NW-SE structures should be particularly promising drilling targets. Frequency versus length and aperture plots of fractures across six to eight orders of magnitude show power-law relationships with a change in scaling exponent in the region of 100 to 500m length-scales. Finally, evaluation of the topology of the fracture branches shows the dominance of Y-nodes that are mostly doubly connected suggesting good connectivity and permeability within the fracture networks. The results obtained in this study illustrate the value of methods that can be globally applied during exploration to better characterize fracture systems in geothermal reservoirs using multiscale datasets.

Hot and steamy fractures in the Philippines: the characterisation and permeability evaluation of fractures of the Southern Negros Geothermal Field, Negros Oriental, Philippines

NASA Astrophysics Data System (ADS)

Pastoriza, Loraine; Holdsworth, Robert; McCaffrey, Kenneth; Dempsey, Eddie; Walker, Richard; Gluyas, Jon; Reyes, Jonathan

2017-04-01

Fluid flow pathway characterisation is critical to geothermal exploration and exploitation. It requires a good understanding of the structural evolution, fault distribution and fluid flow properties. A dominantly fieldwork-based approach has been used to evaluate the potential fracture permeability characteristics of a typical high-temperature geothermal reservoir in the Southern Negros Geothermal Field, Philippines. This is a liquid-dominated geothermal resource hosted in the andesitic to dacitic Quaternary Cuernos de Negros Volcano in Negros Island. Fieldwork reveals two main fracture groups based on fault rock characteristics, alteration type, relative age of deformation, and associated thermal manifestation, with the younger fractures mainly related to the development of the modern geothermal system. Palaeostress analyses of cross-cutting fault and fracture arrays reveal a progressive counterclockwise rotation of stress axes from the (?)Pliocene up to the present-day, which is consistent with the regional tectonic models. A combined slip and dilation tendency analysis of the mapped faults indicates that NW-SE structures should be particularly promising drilling targets. Frequency versus length and aperture plots of fractures across six to eight orders of magnitude show power-law relationships with a change in scaling exponent in the region of 100 to 500m length-scales. Finally, evaluation of the topology of the fracture branches shows the dominance of Y-nodes that are mostly doubly connected suggesting good connectivity and permeability within the fracture networks. The results obtained in this study illustrate the value of methods that can be globally applied during exploration to better characterize fracture systems in geothermal reservoirs using multiscale datasets.

EFFECTS OF METHYLMERCURY ON SPINAL CORD AFFERENTS AND EFFERENTS—A REVIEW

PubMed Central

Colón-Rodríguez, Alexandra; Hannon, Heidi E.; Atchison, William D.

2017-01-01

Methylmercury (MeHg) is an environmental neurotoxicant of public health concern. It readily accumulates in exposed humans, primarily in neuronal tissue. Exposure to MeHg, either acutely or chronically, causes severe neuronal dysfunction in the central nervous system and spinal neurons; dysfunction of susceptible neuronal populations results in neurodegeneration, at least in part through Ca2+-mediated pathways. Biochemical and morphologic changes in peripheral neurons precede those in central brain regions, despite the fact that MeHg readily crosses the blood-brain barrier. Consequently, it is suggested that unique characteristics of spinal cord afferents and efferents could heighten their susceptibility to MeHg toxicity. Transient receptor potential (TRP) ion channels are a class of Ca2+-permeable cation channels that are highly expressed in spinal afferents, among other sensory and visceral organs. These channels can be activated in numerous ways, including directly via chemical irritants or indirectly via Ca2+ release from intracellular storage organelles. Early studies demonstrated that MeHg interacts with heterologous TRPs, though definitive mechanisms of MeHg toxicity on sensory neurons may involve more complex interaction with, and among, differentially-expressed TRP populations. In spinal efferents, glutamate receptors of the N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and possibly kainic acid (KA) classes are thought to play a major role in MeHg-induced neurotoxicity. Specifically, the Ca2+-permeable AMPA receptors, which are abundant in motor neurons, have been identified as being involved in MeHg-induced neurotoxicity. In this review, we will describe the mechanisms that could contribute to MeHg-induced spinal cord afferent and efferent neuronal degeneration, including the possible mediators, such as uniquely expressed Ca2+-permeable ion channels. PMID:28041893

Remediation of PCB contaminated soils in the Canadian Arctic: excavation and surface PRB technology.

PubMed

Kalinovich, Indra; Rutter, Allison; Poland, John S; Cairns, Graham; Rowe, R Kerry

2008-12-15

The site BAF-5 is located on the summit of Resolution Island, Nunavut, just southeast of Baffin Island at 61 degrees 35'N and 60 degrees 40'W. The site was part of a North American military defense system established in the 1950s that became heavily contaminated with PCBs during and subsequent, its operational years. Remediation through excavation of the PCB contaminated soil at Resolution Island began in 1999 and at its completion in 2006 approximately 5 tonnes of pure PCBs in approximately 20,000 m3 of soil were remediated. Remediation strategies were based on both quantity of soil and level of contamination in the soil. Excavation removed 96% of the PCB contaminated soil on site. In 2003, a surface funnel-and-gate permeable reactive barrier was design and constructed to treat the remaining contamination left in rock crevices and inaccessible areas of the site. Excavation had destabilized contaminated soil in the area, enabling contaminant migration through erosion and runoff pathways. The barrier was designed to maximize sedimentation through settling ponds. This bulk removal enabled the treatment of highly contaminated fines and water through a permeable gate. The increased sediment loading during excavation required both modifications to the funnel and a shift to a more permeable, granular system. Granulated activated charcoal was chosen for its ability to both act as a particle retention filter and adsorptive filter. The reduction in mass of PCB and volume of soils trapped by the funnel of the barrier indicate that soils are re-stabilizing. In 2007, nonwoven geotextiles were re-introduced back into the filtration system as fine filtering could be achieved without clogging. Monitoring sites downstream indicate that the barrier system is effective. This paper describes the field progress of PCB remediation at Resolution Island.

Can we model solute transfer in heterogeneous soils with MIM model?

NASA Astrophysics Data System (ADS)

Ben Slimene, Erij; Lassabatere, Laurent; Winiarski, Thierry; Gourdon, Remy

2017-04-01

The fate of pollutants in the vadose zone must be understood, in particular, underneath infiltration basins for an optimum management of these plants. Stormwaters carry pollutants (heavy metals, organics, emerging pollutant like nanoparticles, etc.) and thus constitute a risk for groundwater and soil quality. Most infiltration basins are settled over highly permeable soils that exhibit a strong lithological heterogeneity. The impact of such lithological heterogeneity on flow and solute transfer has already been questioned. Previous studies have already proved that lithological heterogeneity was prone to the establishment of preferential flows. In more details, the concomitance of several materials with contrasting hydraulic properties induces funneled flow at the interfaces between less permeable and more permeable lithofacies. Solutes are then carried by water fluxes quickly along preferential flow pathways and have restricted access to zones far from these pathways. It can clearly be imagined that such pattern could be modeled by a MIM model postulating water fraction into two fractions, one mobile and the other immobile, with solute transport by convection and dispersion in mobile water fraction and solute diffusion at the interface between mobile and immobile water fractions. The application of MIM approach to the case of solute transport in strongly heterogeneous soils may be quite advantageous: simplification of the problem, fewer parameters, ease of modeling, numerical computation, gain in computation time, etc. However, such consistency has never been investigated in details. In this paper, we focus on the possibility to model solute transport in a strongly heterogeneous deposit using MIM model. The deposit has been the subject of intensive campaigns of characterization of its lithology and the hydraulic and hydrodispersive properties of its lithofacies. Numerical computations were performed for a section of deposit 13.5 m wide and 2.5 m deep. Numerical results clearly showed the establishment of preferential flows with funneling mostly under unsaturated conditions. Solute elution at 2.5 m depth was characterized and discussed as a function of solute reactivity. Solutes breakthrough curves show clear evidence of MIM like pattern. In this paper, we clearly demonstrate that MIM model accurately reproduces solute elution at 2.5m depths but also at different depths. MIM approach accuracy is ensured provided that related parameters are optimized as a function of depth, hydric and hydraulic conditions and the contrast in hydraulic parameters of the lithofacies that constitute the deposit.

Gracilaria lemaneiformis polysaccharide as integrin-targeting surface decorator of selenium nanoparticles to achieve enhanced anticancer efficacy.

PubMed

Jiang, Wenting; Fu, Yuanting; Yang, Fang; Yang, Yufeng; Liu, Ting; Zheng, Wenjie; Zeng, Lilan; Chen, Tianfeng

2014-08-27

The poor permeability of glioma parenchyma represents a major limit for antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP), which has a high binding affinity to αvβ3 integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (SeNPs) to achieve antiglioblastoma efficacy. GLP-SeNPs showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. In U87 glioma cell membrane, which has a high integrin expression level, GLP-SeNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP-SeNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP-SeNPs was inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via αvβ3 integrin-mediated endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was enhanced significantly because of the induction of various apoptosis signaling pathways. Internalized GLP-SeNPs triggered intracellular reactive oxygen species downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance cell apoptosis. These findings suggest that surface decoration of nanomaterials with GLP could be an efficient strategy for design and preparation of glioblastoma targeting nanodrugs.

A computational assessment of the permeability and salt rejection of carbon nanotube membranes and their application to water desalination

PubMed Central

Thomas, Michael; Corry, Ben

2016-01-01

Membranes made from nanomaterials such as nanotubes and graphene have been suggested to have a range of applications in water filtration and desalination, but determining their suitability for these purposes requires an accurate assessment of the properties of these novel materials. In this study, we use molecular dynamics simulations to determine the permeability and salt rejection capabilities for membranes incorporating carbon nanotubes (CNTs) at a range of pore sizes, pressures and concentrations. We include the influence of osmotic gradients and concentration build up and simulate at realistic pressures to improve the reliability of estimated membrane transport properties. We find that salt rejection is highly dependent on the applied hydrostatic pressure, meaning high rejection can be achieved with wider tubes than previously thought; while membrane permeability depends on salt concentration. The ideal size of the CNTs for desalination applications yielding high permeability and high salt rejection is found to be around 1.1 nm diameter. While there are limited energy gains to be achieved in using ultra-permeable CNT membranes in desalination by reverse osmosis, such membranes may allow for smaller plants to be built as is required when size or weight must be minimized. There are diminishing returns in further increasing membrane permeability, so efforts should focus on the fabrication of membranes containing narrow or functionalized CNTs that yield the desired rejection or selection properties rather than trying to optimize pore densities. PMID:26712639

Cell permeability beyond the rule of 5.

PubMed

Matsson, Pär; Doak, Bradley C; Over, Björn; Kihlberg, Jan

2016-06-01

Drug discovery for difficult targets that have large and flat binding sites is often better suited to compounds beyond the "rule of 5" (bRo5). However, such compounds carry higher pharmacokinetic risks, such as low solubility and permeability, and increased efflux and metabolism. Interestingly, recent drug approvals and studies suggest that cell permeable and orally bioavailable drugs can be discovered far into bRo5 space. Tactics such as reduction or shielding of polarity by N-methylation, bulky side chains and intramolecular hydrogen bonds may be used to increase cell permeability in this space, but often results in decreased solubility. Conformationally flexible compounds can, however, combine high permeability and solubility, properties that are keys for cell permeability and intestinal absorption. Recent developments in computational conformational analysis will aid design of such compounds and hence prediction of cell permeability. Transporter mediated efflux occurs for most investigated drugs in bRo5 space, however it is commonly overcome by high local intestinal concentrations on oral administration. In contrast, there is little data to support significant impact of transporter-mediated intestinal absorption in bRo5 space. Current knowledge of compound properties that govern transporter effects of bRo5 drugs is limited and requires further fundamental and comprehensive studies. Copyright © 2016 Elsevier B.V. All rights reserved.

A 2D Model of Hydraulic Fracturing, Damage and Microseismicity

NASA Astrophysics Data System (ADS)

Wangen, Magnus

2018-03-01

We present a model for hydraulic fracturing and damage of low-permeable rock. It computes the intermittent propagation of rock damage, microseismic event locations, microseismic frequency-magnitude distributions, stimulated rock volume and the injection pressure. The model uses a regular 2D grid and is based on ideas from invasion percolation. All damaged and connected cells during a time step constitute a microseismic event, where the size of the event is the number of cells in the cluster. The magnitude of the event is the log _{10} of the event size. The model produces events with a magnitude-frequency distribution having a b value that is approximately 0.8. The model is studied with respect to the physical parameters: permeability of damaged rock and the rock strength. "High" permeabilities of the damaged rock give the same b value ≈ 0.8, but "moderate" permeabilities give higher b values. Another difference is that "high" permeabilities produce a percolation-like fracture network, while "moderate" permeabilities result in damage zones that expand circularly away from the injection point. In the latter case of "moderate" permeabilities, the injection pressure increases substantially beyond the fracturing level. The rock strength and the time step do not change the observed b value of the model for moderate changes.

Effective High-Frequency Permeability of Compacted Metal Powders

NASA Astrophysics Data System (ADS)

Volkovskaya, I. I.; Semenov, V. E.; Rybakov, K. I.

2018-03-01

We propose a model for determination of the effective complex permeability of compacted metal-powder media. It is based on the equality of the magnetic moment in a given volume of the media with the desired effective permeability to the total magnetic moment of metal particles in the external high-frequency magnetic field, which arises due to excitation of electric eddy currents in the particles. Calculations within the framework of the proposed model allow us to refine the values of the real and imaginary components of the permeability of metal powder compacts in the microwave band. The conditions of applicability of the proposed model are formulated, and their fulfillment is verified for metal powder compacts in the microwave and millimeter wavelength bands.

Morphological Characterization of Silicone Hydrogels

NASA Astrophysics Data System (ADS)

Gido, Samuel

2007-03-01

Silicone hydrogel materials are used in the latest generation of extended wear soft contact lenses. To ensure comfort and eye health, these materials must simultaneously exhibit high oxygen permeability and high water permeability / hydrophilicity. The materials achieve these opposing requirements based on bicontinuous composite of nanoscale domains of oxygen permeable (silicones) and hydrophilic (water soluble polymer) materials. The microphase separated morphology of silicone hydrogel contact lens materials was imaged using field emission gun scanning transmission electron microscopy (FEGSTEM), and atomic force microscopy (AFM). Additional morphological information was provided by small angle X-ray scattering (SAXS). These results all indicate a nanophase separated structure of silicone rich (oxygen permeable) and carbon rich (water soluble polymer) domains separated on a length scale of about 10 nm.

Apparatus for providing directional permeability measurements in subterranean earth formations

DOEpatents

Shuck, Lowell Z.

1977-01-01

Directional permeability measurements are provided in a subterranean earth formation by injecting a high-pressure gas from a wellbore into the earth formation in various azimuthal directions with the direction having the largest pressure drop being indicative of the maximum permeability direction. These measurements are provided by employing an inflatable boot containing a plurality of conduits in registry with a like plurality of apertures penetrating the housing at circumferentially spaced-apart locations. These conduits are, in turn, coupled through a valved manifold to a source of pressurized gas so that the high-pressure gas may be selectively directed through any conduit into the earth formation defining the bore with the resulting difference in the pressure drop through the various conduits providing the permeability measurements.

Dynamo Enhancement and Mode Selection Triggered by High Magnetic Permeability.

PubMed

Kreuzahler, S; Ponty, Y; Plihon, N; Homann, H; Grauer, R

2017-12-08

We present results from consistent dynamo simulations, where the electrically conducting and incompressible flow inside a cylinder vessel is forced by moving impellers numerically implemented by a penalization method. The numerical scheme models jumps of magnetic permeability for the solid impellers, resembling various configurations tested experimentally in the von Kármán sodium experiment. The most striking experimental observations are reproduced in our set of simulations. In particular, we report on the existence of a time-averaged axisymmetric dynamo mode, self-consistently generated when the magnetic permeability of the impellers exceeds a threshold. We describe a possible scenario involving both the turbulent flow in the vicinity of the impellers and the high magnetic permeability of the impellers.

Numerical Investigation of the Turbulent Wind Flow Through Elevated Windbreak

NASA Astrophysics Data System (ADS)

Agarwal, Ashish; Irtaza, Hassan

2018-06-01

Analysis of airflow through elevated windbreaks is presented in this paper. Permeable nets and impermeable film increases considerable wind forces on the windbreaks which is susceptible to damage during high wind. A comprehensive numerical investigation has been carried out to analyze the effects of wind on standalone elevated windbreak clad with various permeable nets and an impermeable film. The variation of airflow behavior around and through permeable nets and airflow behavior around impermeable film were also been investigated. Computational fluid dynamics techniques using Reynolds Averaged Navier-Stokes equations has been used to predict the wind force coefficient and thus wind forces on panels supporting permeable nets and impermeable film for turbulent wind flow. Elevated windbreak panels were analyzed for seven different permeable nets having various solidity ratio, specific permeability and aerodynamic resistant coefficients. The permeable nets were modelled as porous jump media obeying Forchheimer's law and an impermeable film modelled as rigid wall.

Numerical Investigation of the Turbulent Wind Flow Through Elevated Windbreak

NASA Astrophysics Data System (ADS)

Agarwal, Ashish; Irtaza, Hassan

2018-04-01

Analysis of airflow through elevated windbreaks is presented in this paper. Permeable nets and impermeable film increases considerable wind forces on the windbreaks which is susceptible to damage during high wind. A comprehensive numerical investigation has been carried out to analyze the effects of wind on standalone elevated windbreak clad with various permeable nets and an impermeable film. The variation of airflow behavior around and through permeable nets and airflow behavior around impermeable film were also been investigated. Computational fluid dynamics techniques using Reynolds Averaged Navier-Stokes equations has been used to predict the wind force coefficient and thus wind forces on panels supporting permeable nets and impermeable film for turbulent wind flow. Elevated windbreak panels were analyzed for seven different permeable nets having various solidity ratio, specific permeability and aerodynamic resistant coefficients. The permeable nets were modelled as porous jump media obeying Forchheimer's law and an impermeable film modelled as rigid wall.

Development of Helium-Mass-Spectrometry-Permeameter for the Measurement of Permeability of Near-Impermeable Rock

NASA Astrophysics Data System (ADS)

Lee, Moo Y.; Bauer, Stephen J.

2016-12-01

A helium leakage detection system was modified to measure gas permeability on extracted cores of nearly impermeable rock. The Helium-Mass-Spectrometry-Permeameter (HMSP) is duplicating the classic Darcy's experiment with a constant pressure differential and steady-state flow through a sample using helium gas. Under triaxial stress condition, the newly developed HMSP can measure hydraulic permeability of rocks and geomaterials down to the nanoDarcy scale (10-21 m2). The extension of measuring the lower end of the permeability scale may help answer important questions regarding the permeability of rock at great depth where fractures may close completely under high lithostatic stress.

Air Permeability of Renovation Plasters Evaluated with Torrent’s Method

NASA Astrophysics Data System (ADS)

Brasse, Krystian; Tracz, Tomasz

2017-10-01

The aim of research was to determine the air permeability of the renovation plasters, using Torrent’s method. The scope of this research included three renovation plaster systems. Each of them was applied on experimental, masonry element and had a different rendering coat. Permeability measurements were performed after 28 days of curing in a natural state. In order to calculate the coefficient of air permeability (kT), the partial data was registered during the measurements. The test results indicate the possibility of determination the coefficient of air permeability kT in relation to the renovation plasters. At the same time results confirm the high porosity of the renovation plasters.

Fluid activity within the North Anatolian Fault Zone according to 3D marine seismic data on the Sea of Marmara Western High

NASA Astrophysics Data System (ADS)

Grall, C.; Henry, P.; Thomas, Y.; Marsset, B.; Westbrook, G.; Saritas, H.; Géli, L.; Ruffine, L.; Dupré, S.; Scalabrin, C.; Augustin, J. M.; Cifçi, G.; Zitter, T.

2012-04-01

Along the northern branch of the North Anatolian Fault Zone (NAFZ) within the Sea of Marmara, numerous gas seeps occur. A large part of the gas origin is biogenic but on the Western High, gas bubbles and gas hydrate with a thermogenic signature have been sampled. The expulsion of deep fluids opened new perspective about the permeability, the mechanical properties and the monitoring of the NAFZ. Consequently, the Western High was selected for the deployment of a 3D seismic acquisition layout during the MARMESONET cruise (2009). Thirty-three km2 of high resolution seismic data (with a frequency content of 50-180 Hz) have been collected within the shear band of the fault. The SIMRAD EM-302 was also operated to detect acoustic anomalies related to the presence of gas bubbles in the water column. Within the upper sedimentary cover (seismic penetration ranges from 100 to 500 m bsf), high seismic amplitude variations of the reflectors allow to identify gas traps and gas pathways. Local high amplitude of negative polarity, such as flat spots and bright spots, are observed. Amplitude anomalies are located above and within anticlines and along normal faults. They often correlate with seafloor manifestations of fluid outflow and gas plumes in the water column. This suggests that gas migrates from depth towards the seafloor along normal faults and permeable strata, and part of it is trapped in anticlines. North of the NAF, seabed mounds, corresponding to active hydrocarbon gas seeps, are aligned along a NE-SW direction. They are linked in depth to buried mud volcanoes with an episodic activity. The last mud eruption activity apparently just before or during the Red-H1 horizon deposition which is a prominent reflector of high amplitude and negative polarity occurring all over the Sea of Marmara. It has been interpreted as a stratigraphic horizon, corresponding to slow sedimentation and high sea-level interglacial period.

Petrophysics of low-permeability medina sandstone, northwestern Pennsylvania, Appalachian Basin

USGS Publications Warehouse

Castle, J.W.; Byrnes, A.P.

1998-01-01

Petrophysical core testing combined with geophysical log analysis of low-permeability, Lower Silurian sandstones of the Appalachian basin provides guidelines and equations for predicting gas producibility. Permeability values are predictable from the borehole logs by applying empirically derived equations based on correlation between in-situ porosity and in-situ effective gas permeability. An Archie-form equation provides reasonable accuracy of log-derived water saturations because of saturated brine salinities and low clay content in the sands. Although measured porosity and permeability average less than 6% and 0.1 mD, infrequent values as high as 18% and 1,048 mD occur. Values of effective gas permeability at irreducible water saturation (Swi) range from 60% to 99% of routine values for the highest permeability rocks to several orders of magnitude less for the lowest permeability rocks. Sandstones having porosity greater than 6% and effective gas permeability greater than 0.01 mD exhibit Swi less than 20%. With decreasing porosity, Swi sharply increases to values near 40% at 3 porosity%. Analysis of cumulative storage and flow capacity indicates zones with porosity greater than 6% generally contain over 90% of flow capacity and hold a major portion of storage capacity. For rocks with Swi < 20%, gas relative permeabilities exceed 45%. Gas relative permeability and hydrocarbon volume decrease rapidly with increasing Swi as porosity drops below 6%. At Swi above 40%, gas relative permeabilities are less than approximately 10%.

Correlation between tunability and anisotropy in magnetoelectric voltage tunable inductor (VTI).

PubMed

Yan, Yongke; Geng, Liwei D; Zhang, Lujie; Gao, Xiangyu; Gollapudi, Sreenivasulu; Song, Hyun-Cheol; Dong, Shuxiang; Sanghadasa, Mohan; Ngo, Khai; Wang, Yu U; Priya, Shashank

2017-11-22

Electric field modulation of magnetic properties via magnetoelectric coupling in composite materials is of fundamental and technological importance for realizing tunable energy efficient electronics. Here we provide foundational analysis on magnetoelectric voltage tunable inductor (VTI) that exhibits extremely large inductance tunability of up to 1150% under moderate electric fields. This field dependence of inductance arises from the change of permeability, which correlates with the stress dependence of magnetic anisotropy. Through combination of analytical models that were validated by experimental results, comprehensive understanding of various anisotropies on the tunability of VTI is provided. Results indicate that inclusion of magnetic materials with low magnetocrystalline anisotropy is one of the most effective ways to achieve high VTI tunability. This study opens pathway towards design of tunable circuit components that exhibit field-dependent electronic behavior.

Design and synthesis of (aza)indolyl maleimide-based covalent inhibitors of glycogen synthase kinase 3β.

PubMed

Yang, Zhimin; Liu, Hui; Pan, Botao; He, Fengli; Pan, Zhengying

2018-05-21

As an important kinase in multiple signal transduction pathways, GSK-3β has been an attractive target for chemical probe discovery and drug development. Compared to numerous reversible inhibitors that have been developed, covalent inhibitors of GSK-3β are noticeably lacking. Here, we report the discovery of a series of covalent GSK-3β inhibitors by optimizing both non-covalent interactions and reactive groups. Among these covalent inhibitors, compound 38b with a mild α-fluoromethyl amide reactive group emerges as a selective and covalent inhibitor against GSK-3β, effectively inhibits the phosphorylation of glycogen synthase and tau protein, and increases β-catenin's levels in living cells. In addition, compound 38b is highly permeable and not a substrate of P-glycoprotein.

Permeability anisotropy in marine mudstones in the Nankai Trough, SW Japan: Implications for hypothesized lateral fluid flow and chemical transport outboard of the trench

NASA Astrophysics Data System (ADS)

Saffer, D. M.; McKiernan, A. W.; Skarbek, R. M.

2008-12-01

Characterizing dewatering pathways and chemical fluxes near and outboard of subduction trenches is important toward understanding early sediment dewatering and devolatilization. Quantifying fluid flow rates also constrains the hydraulic gradients driving flow, and thus ultimately hold implications for pore pressure distribution and fault mechanical strength. We focus on the well-studied Nankai Trough offshore SW Japan, where drilling has sampled the sedimentary section at several boreholes from ~11 km outboard of the trench to 3 km landward. At these drillsites, &δ37Cl data and correlation of distinct extrema in downhole chloride profiles have been interpreted to reflect substantial horizontal fluid flow to >10 km outboard of the trench within the ~400 m-thick, homogeneous Lower Shikoku Basin (LSB) facies mudstone. The estimated horizontal velocities are 13 ± 5 cm yr-1; the flow is presumably driven by loading during subduction, and mediated by either permeable conduits or strong anisotropy in permeability. However, the pressure gradients and sediment permeabilities necessary for such flow have not been quantified. Here, we address this problem by combining (1) laboratory measurement of horizontal and vertical sediment permeability from a combination of constant rate of strain (CRS) consolidation tests and flow-through measurements on core samples; and (2) numerical models of fluid flow within a cross section perpendicular to the trench. In our models, we assign hydrostatic pressure at the top and seaward edges, a no-flow condition at the base of the sediments, and pore pressures ranging from 40%-100% of lithostatic at the arcward model boundary. We assign sediment permeability on the basis of our laboratory measurements, and evaluate the possible role of thin permeable conduits as well as strong anisotropy in the incoming section. Our laboratory results define a systematic log-linear relationship between sediment permeability and porosity within the LSB mudstones. The overall variation in permeability for our suite of samples is ~1 order of magnitude. Notably, horizontal permeabilities fall within the range of measured vertical permeabilities, and indicate no significant anisotropy. Using laboratory-derived permeability values, simulated horizontal flow rates range from 10-4 to 10-1 cm yr-1, and decrease dramatically with distance seaward of the trench. With permeability anisotropy of 1000x (i.e. kh = 1000kv), simulated flow rates peak at 3 cm yr-1 at the trench, and decrease to 3x10-1 cm yr-1 by 10 km seaward. These flow rates are substantially lower than those inferred from the geochemical data and also lower than the plate convergence rate of 4 cm yr-1, such that net transport of fluids out of the subduction zone is not likely. If discrete conduits are included in our models, permeabilities of ~10-114m2 are required to sustain the inferred flow rates. However, no potential conduits in the LSB were observed by coring or logging- while-drilling. In contrast, net egress of fluids - and associated chemical transport and pressure translation - are plausible at margins where continuous permeable strata are subducting. Overall, our results highlight a major discrepancy between constraints on fluid flow derived from physical hydrogeology and inferences from geochemical data. In this case, we suggest that the chemical signals may be affected by other processes such as in situ clay dehydration and down-section chemical variations.

Coupled Fracture and Flow in Shale in Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Carey, J. W.; Mori, H.; Viswanathan, H.

2014-12-01

Production of hydrocarbon from shale requires creation and maintenance of fracture permeability in an otherwise impermeable shale matrix. In this study, we use a combination of triaxial coreflood experiments and x-ray tomography characterization to investigate the fracture-permeability behavior of Utica shale at in situ reservoir conditions (25-50 oC and 35-120 bars). Initially impermeable shale core was placed between flat anvils (compression) or between split anvils (pure shear) and loaded until failure in the triaxial device. Permeability was monitored continuously during this process. Significant deformation (>1%) was required to generate a transmissive fracture system. Permeability generally peaked at the point of a distinct failure event and then dropped by a factor of 2-6 when the system returned to hydrostatic failure. Permeability was very small in compression experiments (< 1 mD), possibly because of limited fracture connectivity through the anvils. In pure share experiments, shale with bedding planes perpendicular to shear loading developed complex fracture networks with narrow apertures and peak permeability of 30 mD. Shale with bedding planes parallel to shear loading developed simple fractures with large apertures and a peak permeability as high as 1 D. Fracture systems held at static conditions for periods of several hours showed little change in effective permeability at hydrostatic conditions as high as 140 bars. However, permeability of fractured systems was a function of hydrostatic pressure, declining in a pseudo-linear, exponential fashion as pressure increased. We also observed that permeability decreased with increasing fluid flow rate indicating that flow did not follow Darcy's Law, possibly due to non-laminar flow conditions, and conformed to Forscheimer's law. The coupled deformation and flow behavior of Utica shale, particularly the large deformation required to initiate flow, indicates the probable importance of activation of existing fractures in hydraulic fracturing and that these fractures can have adequate permeability for the production of hydrocarbon.

Recovery of ammonia and production of high-grade phosphates from side-stream digester effluents using gas-permeable membranes

USDA-ARS?s Scientific Manuscript database

Phosphorus recovery was combined with ammonia recovery using gas-permeable membranes. In a first step, the ammonia and alkalinity were removed from municipal side-stream wastewater using low-rate aeration and a gas-permeable membrane manifold. In a second step, the phosphorus was removed using magne...

Selective Permeability of PVA Membranes. I: Radiation-Crosslinked Membranes

NASA Technical Reports Server (NTRS)

Katz, Moshe G.; Wydeven, Theodore, Jr.

1981-01-01

The water and salt transport properties of ionizing radiation crosslinked poly(vinyl alcohol) (PVA) membranes were investigated. The studied membranes showed high permeabilities and low selectivities for both water and salt. The results were found to be in accord with a modified solution-diffusion model for transport across the membranes, in which pressure-dependent permeability coefficients are employed.

Selective permeability of PVA membranes. I - Radiation-crosslinked membranes

NASA Technical Reports Server (NTRS)

Katz, M. G.; Wydeven, T., Jr.

1981-01-01

The water and salt transport properties of ionizing radiation crosslinked poly(vinyl alcohol) (PVA) membranes were investigated. The studied membranes showed high permeabilities and low selectivities for both water and salt. The results were found to be in accord with a modified solution-diffusion model for transport across the membranes, in which pressure-dependent permeability coefficients are employed.

BBB-Permeable, Neuroprotective, and Neurotrophic Polysaccharide, Midi-GAGR.

PubMed

Makani, Vishruti; Jang, Yong-Gil; Christopher, Kevin; Judy, Wesley; Eckstein, Jacob; Hensley, Kenneth; Chiaia, Nicolas; Kim, Dong-Shik; Park, Joshua

2016-01-01

An enormous amount of efforts have been poured to find an effective therapeutic agent for the treatment of neurodegenerative diseases including Alzheimer's disease (AD). Among those, neurotrophic peptides that regenerate neuronal structures and increase neuron survival show a promise in slowing neurodegeneration. However, the short plasma half-life and poor blood-brain-barrier (BBB)-permeability of neurotrophic peptides limit their in vivo efficacy. Thus, an alternative neurotrophic agent that has longer plasma half-life and better BBB-permeability has been sought for. Based on the recent findings of neuroprotective polysaccharides, we searched for a BBB-permeable neuroprotective polysaccharide among natural polysaccharides that are approved for human use. Then, we discovered midi-GAGR, a BBB-permeable, long plasma half-life, strong neuroprotective and neurotrophic polysaccharide. Midi-GAGR is a 4.7kD cleavage product of low acyl gellan gum that is approved by FDA for human use. Midi-GAGR protected rodent cortical neurons not only from the pathological concentrations of co-/post-treated free reactive radicals and Aβ42 peptide but also from activated microglial cells. Moreover, midi-GAGR showed a good neurotrophic effect; it enhanced neurite outgrowth and increased phosphorylated cAMP-responsive element binding protein (pCREB) in the nuclei of primary cortical neurons. Furthermore, intra-nasally administered midi-GAGR penetrated the BBB and exerted its neurotrophic effect inside the brain for 24 h after one-time administration. Midi-GAGR appears to activate fibroblast growth factor receptor 1 (FGFR1) and its downstream neurotrophic signaling pathway for neuroprotection and CREB activation. Additionally, 14-day intranasal administration of midi-GAGR not only increased neuronal activity markers but also decreased hyperphosphorylated tau, a precursor of neurofibrillary tangle, in the brains of the AD mouse model, 3xTg-AD. Taken together, midi-GAGR with good BBB-permeability, long plasma half-life, and strong neuroprotective and neurotrophic effects has a great therapeutic potential for the treatment of neurodegenerative diseases, especially AD.

BBB-Permeable, Neuroprotective, and Neurotrophic Polysaccharide, Midi-GAGR

PubMed Central

Makani, Vishruti; Jang, Yong-gil; Christopher, Kevin; Judy, Wesley; Eckstein, Jacob; Hensley, Kenneth; Chiaia, Nicolas; Kim, Dong-Shik; Park, Joshua

2016-01-01

An enormous amount of efforts have been poured to find an effective therapeutic agent for the treatment of neurodegenerative diseases including Alzheimer’s disease (AD). Among those, neurotrophic peptides that regenerate neuronal structures and increase neuron survival show a promise in slowing neurodegeneration. However, the short plasma half-life and poor blood-brain-barrier (BBB)-permeability of neurotrophic peptides limit their in vivo efficacy. Thus, an alternative neurotrophic agent that has longer plasma half-life and better BBB-permeability has been sought for. Based on the recent findings of neuroprotective polysaccharides, we searched for a BBB-permeable neuroprotective polysaccharide among natural polysaccharides that are approved for human use. Then, we discovered midi-GAGR, a BBB-permeable, long plasma half-life, strong neuroprotective and neurotrophic polysaccharide. Midi-GAGR is a 4.7kD cleavage product of low acyl gellan gum that is approved by FDA for human use. Midi-GAGR protected rodent cortical neurons not only from the pathological concentrations of co-/post-treated free reactive radicals and Aβ42 peptide but also from activated microglial cells. Moreover, midi-GAGR showed a good neurotrophic effect; it enhanced neurite outgrowth and increased phosphorylated cAMP-responsive element binding protein (pCREB) in the nuclei of primary cortical neurons. Furthermore, intra-nasally administered midi-GAGR penetrated the BBB and exerted its neurotrophic effect inside the brain for 24 h after one-time administration. Midi-GAGR appears to activate fibroblast growth factor receptor 1 (FGFR1) and its downstream neurotrophic signaling pathway for neuroprotection and CREB activation. Additionally, 14-day intranasal administration of midi-GAGR not only increased neuronal activity markers but also decreased hyperphosphorylated tau, a precursor of neurofibrillary tangle, in the brains of the AD mouse model, 3xTg-AD. Taken together, midi-GAGR with good BBB-permeability, long plasma half-life, and strong neuroprotective and neurotrophic effects has a great therapeutic potential for the treatment of neurodegenerative diseases, especially AD. PMID:26939023

Fault current limiter

DOEpatents

Darmann, Francis Anthony

2013-10-08

A fault current limiter (FCL) includes a series of high permeability posts for collectively define a core for the FCL. A DC coil, for the purposes of saturating a portion of the high permeability posts, surrounds the complete structure outside of an enclosure in the form of a vessel. The vessel contains a dielectric insulation medium. AC coils, for transporting AC current, are wound on insulating formers and electrically interconnected to each other in a manner such that the senses of the magnetic field produced by each AC coil in the corresponding high permeability core are opposing. There are insulation barriers between phases to improve dielectric withstand properties of the dielectric medium.

Distribution of effluent injected into the Boulder Zone of the Floridan aquifer system at the North District Wastewater Treatment Plant, southeastern Florida, 1997–2011

USGS Publications Warehouse

King, Jeffrey N.; Decker, Jeremy D.

2018-02-09

Nonhazardous, secondarily treated, domestic wastewater (effluent) has been injected about 1 kilometer below land surface into the Boulder Zone of the Floridan aquifer system at the North District Wastewater Treatment Plant in southeastern Florida. The Boulder Zone contains saline, nonpotable water. Effluent transport out of the injection zone is a risk of underground effluent injection. At the North District Wastewater Treatment Plant, injected effluent was detected outside the Boulder Zone. The U.S. Geological Survey, in cooperation with Miami-Dade Water and Sewer Department, investigated effluent transport from the Boulder Zone to overlying permeable zones in the Floridan aquifer system.One conceptual model is presented to explain the presence of effluent outside of the injection zone in which effluent injected into the Boulder Zone was transported to the Avon Park permeable zone, forced by buoyancy and injection pressure. In this conceptual model, effluent injected primarily into the Boulder Zone reaches a naturally occurring feature (a karst-collapse structure) near an injection well, through which the effluent is transported vertically upward to the uppermost major permeable zone of the Lower Floridan aquifer. The effluent is then transported laterally through the uppermost major permeable zone of the Lower Floridan aquifer to another naturally occurring feature northwest of the North District Wastewater Treatment Plant, through which it is then transported vertically upward into the Avon Park permeable zone. In addition, a leak within a monitoring well, between monitoring zones, allowed interflow between the Avon Park permeable zone and the Upper Floridan aquifer. A groundwater flow and effluent transport simulation of the hydrogeologic system at the North District Wastewater Treatment Plant, based on the hypothesized and non-unique conceptualization of the subsurface hydrogeology and flow system, generally replicated measured effluent constituent concentration trends. The model was calibrated to match observed concentration trends for total ammonium (NH4+) and total dissolved solids.The investigation qualitatively indicates that fractures, karst-collapse structures, faults, or other hydrogeologic features may permit effluent injected into the Boulder Zone to be transported to overlying permeable zones in the Floridan aquifer system. These findings, however, are qualitative because the locations of transport pathways that might exist from the Boulder Zone to the Avon Park permeable zone are largely unknown.

Study on Biopharmaceutics Classification and Oral Bioavailability of a Novel Multikinase Inhibitor NCE for Cancer Therapy

PubMed Central

Yang, Yang; Fan, Chun-Mei; He, Xuan; Ren, Ke; Zhang, Jin-Kun; He, Ying-Ju; Yu, Luo-Ting; Zhao, Ying-Lan; Gong, Chang-Yang; Zheng, Yu; Song, Xiang-Rong; Zeng, Jun

2014-01-01

Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (Peff) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 μg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10−4 mg·min−1·cm−2. The Peff value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates. PMID:24776763

Study on biopharmaceutics classification and oral bioavailability of a novel multikinase inhibitor NCE for cancer therapy.

PubMed

Yang, Yang; Fan, Chun-Mei; He, Xuan; Ren, Ke; Zhang, Jin-Kun; He, Ying-Ju; Yu, Luo-Ting; Zhao, Ying-Lan; Gong, Chang-Yang; Zheng, Yu; Song, Xiang-Rong; Zeng, Jun

2014-04-25

Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (P(eff)) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 μg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10⁻⁴ mg·min⁻¹·cm⁻². The P(eff) value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates.

The Permeability Transition Pore Controls Cardiac Mitochondrial Maturation and Myocyte Differentiation

PubMed Central

Hom, Jennifer R.; Quintanilla, Rodrigo A.; Hoffman, David L.; Karen L., de Mesy Bentley; Molkentin, Jeffery D.; Sheu, Shey-Shing; Porter, George A.

2011-01-01

SUMMARY Although mature myocytes rely on mitochondria as the primary source of energy, the role of mitochondria in the developing heart is not well known. Here, we find closure of the mitochondrial permeability transition pore (mPTP) drives maturation of mitochondrial structure and function and myocyte differentiation. Cardiomyocytes at embryonic day (E) 9.5, when compared to E13.5, displayed fragmented mitochondria with few cristae, a less polarized mitochondrial membrane potential, higher reactive oxygen species (ROS) levels, and an open mPTP. Pharmacologic and genetic closing of the mPTP yielded maturation of mitochondrial structure and function, lowered ROS, and increased myocyte differentiation (measured by counting Z-bands). Furthermore, myocyte differentiation was inhibited and enhanced with oxidant and antioxidant treatment, respectively, suggesting that redox signaling pathways lie downstream of mitochondria to regulate cardiac myocyte differentiation. PMID:21920313

Effects of metformin treatment on glioma-induced brain edema

PubMed Central

Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

2016-01-01

Considerable evidence has demonstrated that metformin can activate 5’-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo. PMID:27648126

Effects of metformin treatment on glioma-induced brain edema.

PubMed

Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

2016-01-01

Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

Activation of rho is involved in the mechanism of hydrogen-peroxide-induced lung edema in isolated perfused rabbit lung.

PubMed

Chiba, Y; Ishii, Y; Kitamura, S; Sugiyama, Y

2001-09-01

Acute lung injury is attributed primarily to increased vascular permeability caused by reactive oxygen species derived from neutrophils, such as hydrogen peroxide (H2O2). Increased permeability is accompanied by the contraction and cytoskeleton reorganization of endothelial cells, resulting in intercellular gap formation. The Rho family of Ras-like GTPases is implicated in the regulation of the cytoskeleton and cell contraction. We examined the role of Rho in H2O2-induced pulmonary edema with the use of isolated perfused rabbit lungs. To our knowledge, this is the first study to examine the role of Rho in increased vascular permeability induced by H2O2 in perfused lungs. Vascular permeability was evaluated on the basis of the capillary filtration coefficient (Kfc, ml/min/cm H2O/100 g). We found that H2O2 (300 microM) increased lung weight, Kfc, and pulmonary capillary pressure. These effects of H2O2 were abolished by treatment with Y-27632 (50 microM), an inhibitor of the Rho effector p160 ROCK. In contrast, the muscular relaxant papaverine inhibited the H2O2-induced rise in pulmonary capillary pressure, but did not suppress the increases in lung weight and Kfc. These findings indicate that H2O2 causes pulmonary edema by elevating hydrostatic pressure and increasing vascular permeability. Y-27632 inhibited the formation of pulmonary edema by blocking both of these H2O2-induced effects. Our results suggest that Rho-related pathways have a part in the mechanism of H2O2-induced pulmonary edema. Copyright 2001 Academic Press.

Gas separation performance of carbon molecular sieve membranes based on 6FDA-mPDA/DABA (3:2) polyimide.

PubMed

Qiu, Wulin; Zhang, Kuang; Li, Fuyue Stephanie; Zhang, Ke; Koros, William J

2014-04-01

6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The membranes were characterized with thermogravimetric analysis, FTIR spectroscopy, wide-angle X-ray diffraction, and gas permeation tests. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes were discussed in relation to pyrolysis protocols. The uncross-linked polymer membranes showed high CO2 /CH4 selectivity, whereas thermally crosslinked membranes exhibited significantly improved CO2 permeability and excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2 permeability and CO2 /CH4 selectivity. An increase in the pyrolysis temperature resulted in CMS membranes with lower gas permeability but higher selectivity. The 550 °C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750 Barrer with CO2 /CH4 selectivity of approximately 52. Even 800 °C pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with high CO2 /CH4 selectivity of approximately 118. Both polymer membranes and the CMS membranes are very attractive in aggressive natural gas purification applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In silico and in vitro prediction of gastrointestinal absorption from potential drug eremantholide C.

PubMed

Caldeira, Tamires G; Saúde-Guimarães, Dênia A; Dezani, André B; Serra, Cristina Helena Dos Reis; de Souza, Jacqueline

2017-11-01

Analysis of the biopharmaceutical properties of eremantholide C, sesquiterpene lactone with proven pharmacological activity and low toxicity, is required to evaluate its potential to become a drug. Preliminary analysis of the physicochemical characteristics of eremantholide C was performed in silico. Equilibrium solubility was evaluated using the shake-flask method, at 37.0 °C, 100 rpm during 72 h in biorelevant media. The permeability was analysed using parallel artificial membrane permeability assay, at 37.0 °C, 50 rpm for 5 h. The donor compartment was composed of an eremantholide C solution in intestinal fluid simulated without enzymes, while the acceptor compartment consisted of phosphate buffer. Physicochemical characteristics predicted in silico indicated that eremantholide C has a low solubility and high permeability. In-vitro data of eremantholide C showed low solubility, with values for the dose/solubility ratio (ml): 9448.82, 10 389.61 e 15 000.00 for buffers acetate (pH 4.5), intestinal fluid simulated without enzymes (pH 6.8) and phosphate (pH 7.4), respectively. Also, it showed high permeability, with effective permeability of 30.4 × 10 -6 cm/s, a higher result compared with propranolol hydrochloride (9.23 × 10 -6 cm/s). The high permeability combined with its solubility, pharmacological activity and low toxicity demonstrate the importance of eremantholide C as a potential drug candidate. © 2017 Royal Pharmaceutical Society.

Analytical solutions of one-dimensional multispecies reactive transport in a permeable reactive barrier-aquifer system

NASA Astrophysics Data System (ADS)

Mieles, John; Zhan, Hongbin

2012-06-01

The permeable reactive barrier (PRB) remediation technology has proven to be more cost-effective than conventional pump-and-treat systems, and has demonstrated the ability to rapidly reduce the concentrations of specific chemicals of concern (COCs) by up to several orders of magnitude in some scenarios. This study derives new steady-state analytical solutions to multispecies reactive transport in a PRB-aquifer (dual domain) system. The advantage of the dual domain model is that it can account for the potential existence of natural degradation in the aquifer, when designing the required PRB thickness. The study focuses primarily on the steady-state analytical solutions of the tetrachloroethene (PCE) serial degradation pathway and secondly on the analytical solutions of the parallel degradation pathway. The solutions in this study can also be applied to other types of dual domain systems with distinct flow and transport properties. The steady-state analytical solutions are shown to be accurate and the numerical program RT3D is selected for comparison. The results of this study are novel in that the solutions provide improved modeling flexibility including: 1) every species can have unique first-order reaction rates and unique retardation factors, and 2) daughter species can be modeled with their individual input concentrations or solely as byproducts of the parent species. The steady-state analytical solutions exhibit a limitation that occurs when interspecies reaction rate factors equal each other, which result in undefined solutions. Excel spreadsheet programs were created to facilitate prompt application of the steady-state analytical solutions, for both the serial and parallel degradation pathways.

Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease

PubMed Central

Hannemann, Anke; Cytlak, Urszula M; Rees, David C; Tewari, Sanjay; Gibson, John S

2014-01-01

The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with the abnormal form of haemoglobin (Hb), HbS, in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization and RBC sickling during hypoxia. We hypothesized that should 5HMF also inhibit the main cation pathways implicated in the dehydration of RBCs from SCD patients – the deoxygenation-induced cation pathway (Psickle), the Ca2+-activated K+ channel (the Gardos channel) and the K+–Cl− cotransporter (KCC) – it would have a synergistic effect in protection against sickling, directly through interacting with HbS, and indirectly through maintaining hydration and reducing [HbS]. This study was therefore designed to investigate the effects of 5HMF on RBC volume and K+ permeability in vitro. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation/re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca2+ through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N-ethylmaleimide (NEM, 1 mm)-treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis. PMID:25015917

Combined interpretation of radar, hydraulic, and tracer data from a fractured-rock aquifer near Mirror Lake, New Hampshire, USA

USGS Publications Warehouse

Day-Lewis, F. D.; Lane, J.W.; Gorelick, S.M.

2006-01-01

An integrated interpretation of field experimental cross-hole radar, tracer, and hydraulic data demonstrates the value of combining time-lapse geophysical monitoring with conventional hydrologic measurements for improved characterization of a fractured-rock aquifer. Time-lapse difference-attenuation radar tomography was conducted during saline tracer experiments at the US Geological Survey Fractured Rock Hydrology Research Site near Mirror Lake, Grafton County, New Hampshire, USA. The presence of electrically conductive saline tracer effectively illuminates permeable fractures or pathways for geophysical imaging. The geophysical results guide the construction of three-dimensional numerical models of ground-water flow and solute transport. In an effort to explore alternative explanations for the tracer and tomographic data, a suite of conceptual models involving heterogeneous hydraulic conductivity fields and rate-limited mass transfer are considered. Calibration data include tracer concentrations, the arrival time of peak concentration at the outlet, and steady-state hydraulic head. Results from the coupled inversion procedure suggest that much of the tracer mass migrated outside the three tomographic image planes, and that solute is likely transported by two pathways through the system. This work provides basic and site-specific insights into the control of permeability heterogeneity on ground-water flow and solute transport in fractured rock. ?? Springer-Verlag 2004.

Changes in migration mode of brine and supercritical CO2 in imbibition process under steady flow state of very slow fluid velocities

NASA Astrophysics Data System (ADS)

Kogure, Tetsuya; Zhang, Yi; Nishizawa, Osamu; Xue, Ziqiu

2018-05-01

Relative permeability curves and flow mechanisms of CO2 and brine in Berea sandstone were investigated during a two-phase flow imbibition process, where CO2 saturation in the rock decreased from 55 per cent to 9 per cent by stepwise decrease of CO2/brine injection ratios. Total fluid flow velocity was 4.25 × 10-6 m/s, corresponding to the capillary number of order ˜10-8 for CO2 flow. The relative permeability curves showed a slight hysteresis compared to those during the drainage process. Local CO2 saturation and the differential pressure showed temporal fluctuations when the average differential pressure showed constant values or very small trends. The fluctuations in local CO2 saturation correlate with local porosity distributions. The differential pressure between the inlet and outlet ends showed the largest fluctuation when the CO2/brine ratio equals to one. A final brine-only injection resulted in more CO2 trapped within low porosity zones. These results suggest important roles of ganglion dynamics in the low flow rate ranges, where fluid pathways undergo repetitive brine snap-off and coalescence of CO2 ganglia that causes morphological changes in distributions of CO2 pathways.

Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shibuya, Masabumi; Claesson-Welsh, Lena

2006-03-10

The VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates. VEGF-A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). VEGFR1, which occurs in transmembrane and soluble forms, negatively regulates vasculogenesis and angiogenesis during early embryogenesis, but it also acts as a positive regulator of angiogenesis and inflammatory responses, playing a role in several human diseases such as rheumatoid arthritis and cancer. The soluble VEGFR1 is overexpressed in placenta in preeclampsia patients. VEGFR2 has critical functions in physiological and pathologicalmore » angiogenesis through distinct signal transduction pathways regulating proliferation and migration of endothelial cells. VEGFR3, a receptor for the lymphatic growth factors VEGF-C and VEGF-D, but not for VEGF-A, regulates vascular and lymphatic endothelial cell function during embryogenesis. Loss-of-function variants of VEGFR3 have been identified in lymphedema. Formation of tumor lymphatics may be stimulated by tumor-produced VEGF-C, allowing increased spread of tumor metastases through the lymphatics. Mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases.« less

Effects of eddy current and dispersion of magnetic anisotropy on the high-frequency permeability of Fe-based nanocomposites

NASA Astrophysics Data System (ADS)

Han, M.; Rozanov, K. N.; Zezyulina, P. A.; Wu, Yan-Hui

2015-06-01

Fe-Cu-Nb-Si-B microflakes have been prepared by ball milling. The structural, magnetostatic and microwave permeability of the flakes and flake-filled composites have been studied. Two ferromagnetic phases, nanograins and amorphous matrix, are found in the flakes. The Mössbauer study shows that the nanograins are α-Fe3(Si) with D03 superlattice structure. High resolution transmission electron microscopy shows that the nanograins are well dispersed in the matrix. The microwave permeability of composites containing the flakes has been measured. The comparison of the intrinsic permeability of the flakes obtained from the permeability measurements and from the anisotropy field distribution reveals a disagreement in the magnetic loss peak location. It is concluded that the low-frequency loss in the composites is not due to the effect of eddy currents. The low-frequency loss may be attributed to other sources, such as domain wall motion or peculiarities of the magnetic structure of the flakes in the composite.

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.

PubMed

Vazana, Udi; Veksler, Ronel; Pell, Gaby S; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio; Friedman, Alon

2016-07-20

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. Copyright © 2016 the authors 0270-6474/16/367727-13$15.00/0.

Advantageous Solubility-Permeability Interplay When Using Amorphous Solid Dispersion (ASD) Formulation for the BCS Class IV P-gp Substrate Rifaximin: Simultaneous Increase of Both the Solubility and the Permeability.

PubMed

Beig, Avital; Fine-Shamir, Noa; Lindley, David; Miller, Jonathan M; Dahan, Arik

2017-05-01

Rifaximin is a BCS class IV (low-solubility, low-permeability) drug and also a P-gp substrate. The aims of this work were to assess the efficiency of different rifaximin amorphous solid dispersion (ASDs) formulations in achieving and maintaining supersaturation and to investigate the consequent solubility-permeability interplay. Spray-dried rifaximin ASDs were prepared with different hydrophilic polymers and their ability to achieve and maintain supersaturation was assessed. Then, rifaximin's apparent intestinal permeability was investigated as a function of increasing supersaturation both in vitro using the parallel artificial membrane permeability assay (PAMPA) and in vivo using the single-pass rat intestinal perfusion (SPIP) model. The efficiency of the different ASDs to achieve and maintain supersaturation of rifaximin was found to be highly polymer dependent, and the copovidone/HPC-SL formulation was found to be superior to the other two, allowing supersaturation of 200× that of the crystalline solubility for 20 h. In vitro, rifaximin flux was increased and the apparent permeability was constant as a function of increasing supersaturation level. In vivo, on the other hand, absorption rate coefficient (k a ) was first constant as a function of increasing supersaturation, but at 250×, the crystalline solubility k a was doubled, similar to the k a in the presence of the strong P-gp inhibitor GF120918. In conclusion, a new and favorable nature of solubility-permeability interplay was revealed in this work: delivering high supersaturation level of the BCS class IV drug rifaximin via ASD, thereby saturating the drugs' P-gp-mediated efflux transport, led to the favorable unique win-win situation, where both the solubility and the permeability increased simultaneously.

Glutamate-Mediated Blood–Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery

PubMed Central

Vazana, Udi; Veksler, Ronel; Pell, Gaby S.; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio

2016-01-01

The blood–brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood–brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood–brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo. Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood–brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood–brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT In this study, we reveal a new mechanism that governs blood–brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. PMID:27445149

Polyethylene glycol versus dual sugar assay for gastrointestinal permeability analysis: is it time to choose?

PubMed

van Wijck, Kim; Bessems, Babs Afm; van Eijk, Hans Mh; Buurman, Wim A; Dejong, Cornelis Hc; Lenaerts, Kaatje

2012-01-01

Increased intestinal permeability is an important measure of disease activity and prognosis. Currently, many permeability tests are available and no consensus has been reached as to which test is most suitable. The aim of this study was to compare urinary probe excretion and accuracy of a polyethylene glycol (PEG) assay and dual sugar assay in a double-blinded crossover study to evaluate probe excretion and the accuracy of both tests. Gastrointestinal permeability was measured in nine volunteers using PEG 400, PEG 1500, and PEG 3350 or lactulose-rhamnose. On 4 separate days, permeability was analyzed after oral intake of placebo or indomethacin, a drug known to increase intestinal permeability. Plasma intestinal fatty acid binding protein and calprotectin levels were determined to verify compromised intestinal integrity after indomethacin consumption. Urinary samples were collected at baseline, hourly up to 5 hours after probe intake, and between 5 and 24 hours. Urinary excretion of PEG and sugars was determined using high-pressure liquid chromatography-evaporative light scattering detection and liquid chromatography-mass spectrometry, respectively. Intake of indomethacin increased plasma intestinal fatty acid-binding protein and calprotectin levels, reflecting loss of intestinal integrity and inflammation. In this state of indomethacin-induced gastrointestinal compromise, urinary excretion of the three PEG probes and lactulose increased compared with placebo. Urinary PEG 400 excretion, the PEG 3350/PEG 400 ratio, and the lactulose/rhamnose ratio could accurately detect indomethacin-induced increases in gastrointestinal permeability, especially within 2 hours of probe intake. Hourly urinary excretion and diagnostic accuracy of PEG and sugar probes show high concordance for detection of indomethacin-induced increases in gastrointestinal permeability. This comparative study improves our knowledge of permeability analysis in man by providing a clear overview of both tests and demonstrates equivalent performance in the current setting.

Measurements on stress dependent permeability

NASA Astrophysics Data System (ADS)

Risnes, R.; Faldaas, I.; Korsnes, R. I.; Norland, T.

2003-04-01

Hydrostatic loading is the conventional test procedure to determine the stress dependence of permeability. However, hydrostatic tests do not truly reflect the deviatoric stress state that exists in most reservoirs. The main objective of the present project was to study permeability changes under deviatoric stresses, like encountered in standard triaxial tests. However in measuring permeability in a triaxial cell, end effects may be important. The friction between the axial steel pistons and the sample may cause stress concentrations and thereby a non-homogeneous strain pattern towards the sample ends. To overcome this problem, the cell was modified to have pressure outlets from the mid-section of the sample, with the pressure tubes connected to the outside of the cell for pressure recording. The cell was designed for 1.5 in plugs with plug lengths of about 80 mm. Tests have been performed on two types of high porosity outcrop chalk: Liège chalk with porosity around 40 percent and permeability 1-2 millidarcy, and Aalborg chalk with porosity around 45 percent and permeability in the range 3-5 millidarcy. Methanol was used as saturating fluid for the chalks. In addition some sandstone samples from core material were included. The porosity values were rather high, around 30 percent, and the permeability ranged from around 50 millidarcy to over one Darcy. Synthetic oil was used as saturating fluid for the sandstone samples, to avoid any reactions with clay minerals. The results so far can be summarized as follows:(1) In almost all the tests, the permeability calculated by the overall pressure drop is smaller than the mid-section permeability. The reduction could typically be around 20 percent. This means that end-effects play an important role.(2) The permeability generally decrease with increasing hydrostatic stresses. This is in agreement with observations from other sources.(3) During deviatoric phases the average stress level is increasing, but the changes in permeability are rather small, even if the tests are run beyond yield. The mid-section permeability seems to show a small increasing trend with increasing deviatoric stresses after yield. But the yield point does not seem to have any drastic effect on the permeability.(4) The overall permeability seems in general to show a decreasing trend under deviatoric stresses. The results indicate that permeability changes with pressure depletion under reservoir conditions may be much less than expected from hydrostatic tests or tests uncorrected for end-effects.

Permeability of continental crust influenced by internal and external forcing

USGS Publications Warehouse

Rojstaczer, S.A.; Ingebritsen, S.E.; Hayba, D.O.

2008-01-01

The permeability of continental crust is so highly variable that it is often considered to defy systematic characterization. However, despite this variability, some order has been gleaned from globally compiled data. What accounts for the apparent coherence of mean permeability in the continental crust (and permeability-depth relations) on a very large scale? Here we argue that large-scale crustal permeability adjusts to accommodate rates of internal and external forcing. In the deeper crust, internal forcing - fluxes induced by metamorphism, magmatism, and mantle degassing - is dominant, whereas in the shallow crust, external forcing - the vigor of the hydrologic cycle - is a primary control. Crustal petrologists have long recognized the likelihood of a causal relation between fluid flux and permeability in the deep, ductile crust, where fluid pressures are typically near-lithostatic. It is less obvious that such a relation should pertain in the relatively cool, brittle upper crust, where near-hydrostatic fluid pressures are the norm. We use first-order calculations and numerical modeling to explore the hypothesis that upper-crustal permeability is influenced by the magnitude of external fluid sources, much as lower-crustal permeability is influenced by the magnitude of internal fluid sources. We compare model-generated permeability structures with various observations of crustal permeability. ?? 2008 The Authors Journal compilation ?? 2008 Blackwell Publishing Ltd.

Biowaiver or Bioequivalence: Ambiguity in Sildenafil Citrate BCS Classification.

PubMed

Miranda, Claudia; Pérez-Rodríguez, Zenia; Hernández-Armengol, Rosario; Quiñones-García, Yaidel; Betancourt-Purón, Tania; Cabrera-Pérez, Miguel Ángel

2018-05-01

The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its "high permeability" suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1.2-6.8 at a temperature of 37 °C in aqueous media. The intestinal permeability was determined in rat by a closed-loop in situ perfusion method (the Doluisio technique). The solubility of sildenafil citrate is pH-dependent and at pH 6.8 the dose/solubility ratio obtained does not meet the WHO criteria for "high solubility." The high permeability values obtained by in situ intestinal perfusion in rat reinforce the published permeability data for sildenafil citrate. The experimental results obtained and the data available in the literature suggest that sildenafil citrate is clearly a Class II of BCS, according to the current biopharmaceutics classification system and WHO guidance.

Unified pipe network method for simulation of water flow in fractured porous rock

NASA Astrophysics Data System (ADS)

Ren, Feng; Ma, Guowei; Wang, Yang; Li, Tuo; Zhu, Hehua

2017-04-01

Rock masses are often conceptualized as dual-permeability media containing fractures or fracture networks with high permeability and porous matrix that is less permeable. In order to overcome the difficulties in simulating fluid flow in a highly discontinuous dual-permeability medium, an effective unified pipe network method is developed, which discretizes the dual-permeability rock mass into a virtual pipe network system. It includes fracture pipe networks and matrix pipe networks. They are constructed separately based on equivalent flow models in a representative area or volume by taking the advantage of the orthogonality of the mesh partition. Numerical examples of fluid flow in 2-D and 3-D domain including porous media and fractured porous media are presented to demonstrate the accuracy, robustness, and effectiveness of the proposed unified pipe network method. Results show that the developed method has good performance even with highly distorted mesh. Water recharge into the fractured rock mass with complex fracture network is studied. It has been found in this case that the effect of aperture change on the water recharge rate is more significant in the early stage compared to the fracture density change.

Improved CO sub 2 enhanced oil recovery -- Mobility control by in-situ chemical precipitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ameri, S.; Aminian, K.; Wasson, J.A.

1991-06-01

The overall objective of this study has been to evaluate the feasibility of chemical precipitation to improve CO{sub 2} sweep efficiency and mobility control. The laboratory experiments have indicated that carbonate precipitation can alter the permeability of the core samples under reservoir conditions. Furthermore, the relative permeability measurements have revealed that precipitation reduces the gas permeability in favor of liquid permeability. This indicates that precipitation is occurring preferentially in the larger pores. Additional experimental work with a series of connected cores have indicated that the permeability profile can be successfully modified. However, Ph control plays a critical role in propagationmore » of the chemical precipitation reaction. A numerical reservoir model has been utilized to evaluate the effects of permeability heterogeneity and permeability modification on the CO{sub 2} sweep efficiency. The computer simulation results indicate that the permeability profile modification can significantly enhance CO{sub 2} vertical and horizontal sweep efficiencies. The scoping studies with the model have further revealed that only a fraction of high permeability zones need to be altered to achieve sweep efficiency enhancement. 64 refs., 30 figs., 16 tabs.« less

Porins in the Cell Wall of Mycobacteria

NASA Astrophysics Data System (ADS)

Trias, Joaquim; Jarlier, Vincent; Benz, Roland

1992-11-01

The cell wall of mycobacteria is an efficient permeability barrier that makes mycobacteria naturally resistant to most antibiotics. Liposome swelling assays and planar bilayer experiments were used to investigate the diffusion process of hydrophilic molecules through the cell wall of Mycobacterium chelonae and identify the main hydrophilic pathway. A 59-kilodalton cell wall protein formed a water-filled channel with a diameter of 2.2 nanometers and an average single-channel conductance equal to 2.7 nanosiemens in 1 M potassium chloride. These results suggest that porins can be found in the cell wall of a Gram-positive bacterium. A better knowledge of the hydrophilic pathways should help in the design of more effective antimycobacterial agents.

Screening of pharmacokinetic properties of fifty dihydropyrimidin(thi)one derivatives using a combo of in vitro and in silico assays.

PubMed

Matias, Mariana; Fortuna, Ana; Bicker, Joana; Silvestre, Samuel; Falcão, Amílcar; Alves, Gilberto

2017-11-15

The heterocycles dihydropyrimidin(thi)ones have been under intensive pharmacological research, but their pharmacokinetic properties remain almost unknown. Herein, fifty dihydropyrimidin(thi)ones were submitted to in vitro screening tests using parallel artificial membrane permeability assays (PAMPA) to evaluate their apparent permeability (Papp) through intestinal membrane and blood-brain barrier models, and cell-based assays to assess their interference on the efflux transporter P-glycoprotein (P-gp). Moreover, a set of kinetic and toxicological parameters was also estimated employing a new computational tool, the pkCSM. The in vitro results suggested that 82% of the test compounds have good intestinal permeability (Papp>1.1×10 -6 cm/s), and 66% of these are also expected to exhibit good permeability through blood-brain barrier (Papp>2.0×10 -6 cm/s); these findings are consistent with a high transport rate by passive transcellular pathway. In both PAMPA models, thiourea derivatives presented higher Papp values than the respective urea analogues, which were further corroborated by in silico predictions. The in vitro results also suggested a low extent of plasma protein binding for all compounds (Papp<1.0×10 -5 cm/s), and these findings were also supported by in silico data (unbound fraction ranging from 0.13 to 0.59). In addition, although approximately half of the compounds did not modulate P-gp at the tested concentrations (10 and 50μM), nine of them presented a trend to induce P-gp and particularly the chlorinated compounds exhibited a marked P-gp inhibition at 50μM. Furthermore, the in silico predictions suggested that half of the compounds have hepatotoxic potential. Overall, within this group of compounds, the thiourea derivatives containing an unsubstituted or a monosubstituted (NO 2 , CH 3 , OCH 3 ) phenyl ring attached to the position 4 of the dihydropyrimidine ring represented the most promising structures and should be considered in the subsequent studies of the development of new structurally related drug candidates. Copyright © 2017 Elsevier B.V. All rights reserved.

Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

PubMed

Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

2016-09-02

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability

NASA Astrophysics Data System (ADS)

Palomba, R.; Parodi, A.; Evangelopoulos, M.; Acciardo, S.; Corbo, C.; De Rosa, E.; Yazdi, I. K.; Scaria, S.; Molinaro, R.; Furman, N. E. Toledano; You, J.; Ferrari, M.; Salvatore, F.; Tasciotti, E.

2016-10-01

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

Patch clamp reveals powerful blockade of the mitochondrial permeability transition pore by the D2-receptor agonist pramipexole.

PubMed

Sayeed, Iqbal; Parvez, Suhel; Winkler-Stuck, Kirstin; Seitz, Gordon; Trieu, Isabelle; Wallesch, Claus-Werner; Schönfeld, Peter; Siemen, Detlef

2006-03-01

The dopamine-D2-agonist pramipexole (PPX) was tested for blocking mitochondrial permeability transition (PT) in order to give a possible explanation for its neuroprotective effect seen in PPX-treated Parkinson's disease patients. Patch-clamp techniques for studying single-channel currents in the inner mitochondrial membrane and large-amplitude swelling of energized mitochondria were used to study PPX action on the permeability transition pore (PTP), a key player in the mitochondrial route of the apoptotic cascade. Identity of the PTP was proven by measuring the concentration-response relation for cyclosporin A-blockade (IC50=26 nM). PPX inhibits the PTP reversibly with an IC50 of 500 nM, which is close to the values determined earlier as plasma concentrations after PPX medication in patients. Interaction of PPX with the PTP is further supported by demonstrating that it abolished Ca2+-triggered swelling in functionally intact mitochondria. Blockade of the PTP by PPX was attenuated by increasing concentrations of inorganic phosphate and by acidification. We suggest that PPX could exert part of its neuroprotective effect by inhibition of the PTP and thus, probably, blocking of the mitochondrial pathway of the apoptosis cascade.

Endothelial glycocalyx: permeability barrier and mechanosensor.

PubMed

Curry, F E; Adamson, R H

2012-04-01

Endothelial cells are covered with a polysaccharide rich layer more than 400 nm thick, mechanical properties of which limit access of circulating plasma components to endothelial cell membranes. The barrier properties of this endothelial surface layer are deduced from the rate of tracer penetration into the layer and the mechanics of red and white cell movement through capillary microvessels. This review compares the mechanosensor and permeability properties of an inner layer (100-150 nm, close to the endothelial membrane) characterized as a quasi-periodic structure which accounts for key aspects of transvascular exchange and vascular permeability with those of the whole endothelial surface layers. We conclude that many of the barrier properties of the whole surface layer are not representative of the primary fiber matrix forming the molecular filter determining transvascular exchange. The differences between the properties of the whole layer and the inner glycocalyx structures likely reflect dynamic aspects of the endothelial surface layer including tracer binding to specific components, synthesis and degradation of key components, activation of signaling pathways in the endothelial cells when components of the surface layer are lost or degraded, and the spatial distribution of adhesion proteins in microdomains of the endothelial cell membrane.

Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

PubMed Central

Badhan, Raj K. Singh; Chenel, Marylore; Penny, Jeffrey I.

2014-01-01

Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways. PMID:24647103

Quantification of Water Flux in Vesicular Systems.

PubMed

Hannesschläger, Christof; Barta, Thomas; Siligan, Christine; Horner, Andreas

2018-06-04

Water transport across lipid membranes is fundamental to all forms of life and plays a major role in health and disease. However, not only typical water facilitators like aquaporins facilitate water flux, but also transporters, ion channels or receptors represent potent water pathways. The efforts directed towards a mechanistic understanding of water conductivity determinants in transmembrane proteins, the development of water flow inhibitors, and the creation of biomimetic membranes with incorporated membrane proteins or artificial water channels depend on reliable and accurate ways of quantifying water permeabilities P f . A conventional method is to subject vesicles to an osmotic gradient in a stopped-flow device: Fast recordings of scattered light intensity are converted into the time course of vesicle volume change. Even though an analytical solution accurately acquiring P f from scattered light intensities exists, approximations potentially misjudging P f by orders of magnitude are used. By means of computational and experimental data we point out that erroneous results such as that the single channel water permeability p f depends on the osmotic gradient are direct results of such approximations. Finally, we propose an empirical solution of which calculated permeability values closely match those calculated with the analytical solution in the relevant range of parameters.

Mixed-Matrix Membranes Containing Carbon Nanotubes Composite with Hydrogel for Efficient CO2 Separation.

PubMed

Zhang, Haiyang; Guo, Ruili; Hou, Jinpeng; Wei, Zhong; Li, Xueqin

2016-10-26

In this study, a carbon nanotubes composite coated with N-isopropylacrylamide hydrogel (NIPAM-CNTs) was synthesized. Mixed-matrix membranes (MMMs) were fabricated by incorporating NIPAM-CNTs composite filler into poly(ether-block-amide) (Pebax MH 1657) matrix for efficient CO 2 separation. The as-prepared NIPAM-CNTs composite filler mainly plays two roles: (i) The extraordinary smooth one-dimensional nanochannels of CNTs act as the highways to accelerate CO 2 transport through membranes, increasing CO 2 permeability; (ii) The NIPAM hydrogel layer coated on the outer walls of CNTs acts as the super water absorbent to increase water content of membranes, appealing both CO 2 permeability and CO 2 /gas selectivity. MMM containing 5 wt % NIPAM-CNTs exhibited the highest CO 2 permeability of 567 barrer, CO 2 /CH 4 selectivity of 35, and CO 2 /N 2 selectivity of 70, transcending 2008 Robeson upper bound line. The improved CO 2 separation performance of MMMs is mainly attributed to the construction of the efficient CO 2 transport pathways by NIPAM-CNTs. Thus, MMMs incorporated with NIPAM-CNTs composite filler can be used as an excellent membrane material for efficient CO 2 separation.

Sources, Fluxes, and Effects of Fluids in the Alpine Fault Zone, South Island, New Zealand

NASA Astrophysics Data System (ADS)

Menzies, C. D.; Teagle, D. A. H.; Niedermann, S.; Cox, S.; Craw, D.; Zimmer, M.; Cooper, M. J.; Erzinger, J.

2015-12-01

Historic ruptures on some plate boundary faults occur episodically. Fluids play a key role in modifying the chemical and physical properties of fault zones, which may prime them for repeated rupture by the generation of high pore fluid pressures. Modelling of fluid loss rates from fault zones has led to estimates of fluid fluxes required to maintain overpressure (Faulkner and Rutter, 2001), but fluid sources and fluxes, and permeability evolution in fault zones remain poorly constrained. High mountains in orogenic belts can drive meteoric water to the middle crust, and metamorphic water is generated during rock dehydration. Additionally, fluids from the mantle are transported into the crust when fluid pathways are created by tectonism or volcanism. Here we use geochemical tracers to determine fluid flow budgets for meteoric, metamorphic and mantle fluids at a major compressional tectonic plate boundary. The Alpine Fault marks the transpressional Pacific-Australian plate boundary through South Island of New Zealand, it has historically produced large earthquakes (Mw ~8) and is late in its 329±68 year seismic cycle, having last ruptured in 1717. We present strontium isotope ratios of hot springs and hydrothermal minerals that trace fluid flow paths in and around the Alpine Fault to illustrate that the fluid flow regime is restricted by low cross-fault permeability. Fluid-rock interaction limits cross-fault fluid flow by the precipitating clays and calcite that infill pore spaces and fractures in the Alpine Fault alteration zone. In contrast, helium isotopes ratios measured in hot springs near to the fault (0.15-0.81 RA) indicate the fault acts as a conduit for mantle fluids from below. Mantle fluid fluxes are similar to the San Andreas Fault (<1x10-5 m3m-2/yr) and insufficient to promote fault weakening. The metamorphic fluid flux is of similar magnitude to the mantle flux. The dominant fluid throughout the seismogenic zone is meteoric in origin (secondary mineral δDH2O = -45 to -87 ‰), but fluid channelling into the fault zone is required to maintain high pore fluid pressure that would promote fault weakening. Our results show that meteoric waters are primarily responsible for modifying fault zone permeability and for maintaining high pore fluid pressures that may assist episodic earthquake rupture.

A Guide for Selecting Remedies for Subsurface Releases of Chlorinated Solvents

DTIC Science & Technology

2011-03-01

exception of secondary permeability features (e.g., fractures , root holes, animal burrows), high displacement pressures typically preclude DNAPL from...1 to 40 percent. Fractured media with high matrix porosity are commonly encountered in sedimentary rock (e.g., limestone, dolomite , shale, and...Low Permeability .......... 21 Type III – Granular Media with Moderate to High Heterogeneity ........................ 21 Type IV - Fractured Media

Axial and Radial Permeability Evolutions of Compressed Sandstones: End Effects and Shear-band Induced Permeability Anisotropy

NASA Astrophysics Data System (ADS)

Dautriat, Jeremie; Gland, Nicolas; Guelard, Jean; Dimanov, Alexandre; Raphanel, Jean L.

2009-07-01

The influence of hydrostatic and uniaxial stress states on the porosity and permeability of sandstones has been investigated. The experimental procedure uses a special triaxial cell which allows permeability measurements in the axial and radial directions. The core sleeve is equipped with two pressure samplers placed distant from the ends. They provide mid-length axial permeability measure as opposed to the overall permeability measure, which is based on the flow imposed through the pistons of the triaxial cell. The core sleeve is also equipped to perform flows in two directions transverse to the axis of the sample. Two independent measures of axial and complementary radial permeability are thus obtained. Both Fontainebleau sandstone specimens with a porosity of about 5.8% to 8% and low permeability ranging from 2.5 mD to 30 mD and Bentheimer sandstone with a porosity of 24% and a high permeability of 3 D have been tested. The initial axial permeability values obtained by each method are in good agreement for the Fontainebleau sandstone. The Bentheimer sandstone samples present an axial mid-length permeability 1.6 times higher than the overall permeability. A similar discrepancy is also observed in the radial direction, also it relates essentially to the shape of flow lines induced by the radial flow. All the tested samples have shown a higher stress dependency of overall and radial permeability than mid-length permeability. The effect of compaction damage at the pistons/sample and radial ports/sample interfaces is discussed. The relevance of directional permeability measurements during continuous uniaxial compression loadings has been shown on the Bentheimer sandstone until the failure of the sample. We can efficiently measure the influence of brittle failure associated to dilatant regime on the permeability: It tends to increase in the failure propagation direction and to decrease strongly in the transverse direction.

The use of reflective and permeable pavements as a potential practice for heat island mitigation and stormwater management

NASA Astrophysics Data System (ADS)

Li, H.; Harvey, J. T.; Holland, T. J.; Kayhanian, M.

2013-03-01

To help address the built environmental issues of both heat island and stormwater runoff, strategies that make pavements cooler and permeable have been investigated through measurements and modeling of a set of pavement test sections. The investigation included the hydraulic and thermal performance of the pavements. The permeability results showed that permeable interlocking concrete pavers have the highest permeability (or infiltration rate, ˜0.5 cm s-1). The two permeable asphalt pavements showed the lowest permeability, but still had an infiltration rate of ˜0.1 cm s-1, which is adequate to drain rainwater without generating surface runoff during most typical rain events in central California. An increase in albedo can significantly reduce the daytime high surface temperature in summer. Permeable pavements under wet conditions could give lower surface temperatures than impermeable pavements. The cooling effect highly depends on the availability of moisture near the surface layer and the evaporation rate. The peak cooling effect of watering for the test sections was approximately 15-35 °C on the pavement surface temperature in the early afternoon during summer in central California. The evaporative cooling effect on the pavement surface temperature at 4:00 pm on the third day (25 h after watering) was still 2-7 °C lower compared to that on the second day, without considering the higher air temperature on the third day. A separate and related simulation study performed by UCPRC showed that full depth permeable pavements, if designed properly, can carry both light-duty traffic and certain heavy-duty vehicles while retaining the runoff volume captured from an average California storm event. These preliminarily results indicated the technical feasibility of combined reflective and permeable pavements for addressing the built environment issues related to both heat island mitigation and stormwater runoff management.

Evaluation of Porosity and Permeability for an Oil Prospect, Offshore Vietnam by using Artificial Neural Networks

NASA Astrophysics Data System (ADS)

Bui, H. T.; Ho, L. T.; Ushijima, K.; Nur, A.

2006-12-01

Determination of porosity and permeability plays a key role either in characterization of a reservoir or in development of an oil field. Their distribution helps to predict the major faults or fractured zones that are related to high porosity area in order to reduce drilling hazards. Porosity and permeability of the rock can be determined directly from the core sample or obtained from well log data such as: sonic, density, neutron or resistivity. These input parameters depend not only on porosity (?) but also on the rock matrix, fluids contained in the rocks, clay mineral component, or geometry of pore structures. Therefore, it is not easy to estimate exactly porosity and permeability since having corrected those values by conventional well log interpretation method. In this study, the Artificial Neural Networks (ANNs) have been used to derive porosity and permeability directly from well log data for Vung Dong oil prospect, southern offshore Vietnam. Firstly, we designed a training patterns for ANNs from neutron porosity, bulk density, P-sonic, deep resistivity, shallow resistivity and MSFL log curves. Then, ANNs were trained by core samples data for porosity and permeability. Several ANNs paradigms have been tried on a basis of trial and error. The batch back- propagation algorithm was found more proficient in training porosity network meanwhile the quick propagation algorithm is more effective in the permeability network. Secondly, trained ANNs was tested and applied for real data set of some wells to calculate and reveal the distribution maps of porosity or permeability. Distributions of porosity and permeability have been correlated with seismic data interpretation to map the faults and fractured zones in the study. The ANNs showed good results of porosity and permeability distribution with high reliability, fast, accurate and low cost features. Therefore, the ANNs should be widely applied in oil and gas industry.

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules.

PubMed

Dave, Vivek S; Gupta, Deepak; Yu, Monica; Nguyen, Phuong; Varghese Gupta, Sheeba

2017-02-01

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.

Identifying High Potential Well Targets with 3D Seismic and Mineralogy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mellors, R. J.

2015-10-30

Seismic reflection the primary tool used in petroleum exploration and production, but use in geothermal exploration is less standard, in part due to cost but also due to the challenges in identifying the highly-permeable zones essential for economic hydrothermal systems [e.g. Louie et al., 2011; Majer, 2003]. Newer technology, such as wireless sensors and low-cost high performance computing, has helped reduce the cost and effort needed to conduct 3D surveys. The second difficulty, identifying permeable zones, has been less tractable so far. Here we report on the use of seismic attributes from a 3D seismic survey to identify and mapmore » permeable zones in a hydrothermal area.« less

Transient pressure-pulse decay permeability measurements in the Barnett shale

NASA Astrophysics Data System (ADS)

Bhandari, A. R.; Reece, J.; Cronin, M. B.; Flemings, P. B.; Polito, P. J.

2012-12-01

We conducted transient pressure-pulse decay permeability measurements on core plugs of the Barnett shale using a hydrostatic pressure cell. Core plugs, 3.8 cm in diameter and less than 2.5 cm in length, were prepared from a core obtained at a depth of approximately 2330 m from the Mitchel Energy 2 T. P. Sims well in the Mississippian Barnett Formation (Loucks and Ruppel, 2007). We performed permeability measurements of the core plugs using argon at varying confining pressures in two different directions (perpendicular and parallel to bedding planes). We calculate gas permeability from changes in pressure with time using the analytical solution of the pressure diffusion equation with appropriate boundary conditions for our test setup (Dicker and Smits, 1988). Based on our limited results, we interpret 2 × 10-18 m2 for vertical permeability and 156 × 10-18 m2 for horizontal permeability. We demonstrate an extreme stress dependence of the horizontal flow permeability where permeability decreases from 156 × 10-18 m2 to 2.5 × 10-18 m2 as the confining stress is increased from 3.5 to 35 MPa. These permeability measurements are at the high side of other pulsed permeability measurements in the Barnett shale (Bustin et al. 2008; Vermylen, 2011). Permeabilities calculated from mercury injection capillary pressure curves, using theoretically derived permeability-capillary pressure models based on parallel tubes assumption, are orders of magnitude less than our transient pressure-pulse decay permeability measurements (for example, 3.7×10-21 m2 (this study), 10-21 -10-20 m2 (Sigal, 2007), 10-20 -10-17 m2 (Prince et al., 2010)). We interpret that the high measured permeabilities are due to microfractures in the sample. At this point, we do not know if the microfractures are due to sampling disturbance (stress-relief induced) or represent an in-situ fracture network. Our study illustrates the importance of characterization of microfractures at the core scale to understand better the transport behavior in shale matrix and sealing efficiency of cap rocks. References Bustin et al. (2008), Impact of shale properties on pore structure and storage characteristics, SPE 119892. Dicker and Smits (1988), A practical method for determining permeability from laboratory pressure-pulse decay measurements, SPE 17578. Loucks and Ruppel (2007), Mississippian Barnett Shale: Lithofacies and depositional setting of a deep-water shale gas succession in the Fort Worth Basin, Texas, AAPG 2007. Sigal (2007), Mercury capillary pressure measurements on Barnett core. (http://shale.ou.edu/Home/Publication) Prince et al. (2010), Shale diagenesis and permeability: examples from the Barnett shale and the Marcellus formation, AAPG 2010. Vermylen, J.P. (2011), Geomechanical studies of the Barnett Shale, Texas, USA, PhD thesis, Stanford University.

Friedel-Crafts Crosslinked Highly Sulfonated Polyether Ether Ketone (SPEEK) Membranes for a Vanadium/Air Redox Flow Battery.

PubMed

Merle, Géraldine; Ioana, Filipoi Carmen; Demco, Dan Eugen; Saakes, Michel; Hosseiny, Seyed Schwan

2013-12-30

Highly conductive and low vanadium permeable crosslinked sulfonated poly(ether ether ketone) (cSPEEK) membranes were prepared by electrophilic aromatic substitution for a Vanadium/Air Redox Flow Battery (Vanadium/Air-RFB) application. Membranes were synthesized from ethanol solution and crosslinked under different temperatures with 1,4-benzenedimethanol and ZnCl2 via the Friedel-Crafts crosslinking route. The crosslinking mechanism under different temperatures indicated two crosslinking pathways: (a) crosslinking on the sulfonic acid groups; and (b) crosslinking on the backbone. It was observed that membranes crosslinked at a temperature of 150 °C lead to low proton conductive membranes, whereas an increase in crosslinking temperature and time would lead to high proton conductive membranes. High temperature crosslinking also resulted in an increase in anisotropy and water diffusion. Furthermore, the membranes were investigated for a Vanadium/Air Redox Flow Battery application. Membranes crosslinked at 200 °C for 30 min with a molar ratio between 2:1 (mol repeat unit:mol benzenedimethanol) showed a proton conductivity of 27.9 mS/cm and a 100 times lower VO2+ crossover compared to Nafion.

The ethanol metabolite acetaldehyde increases paracellular drug permeability in vitro and oral bioavailability in vivo.

PubMed

Fisher, Scott J; Swaan, Peter W; Eddington, Natalie D

2010-01-01

Alcohol consumption leads to the production of the highly reactive ethanol metabolite, acetaldehyde, which may affect intestinal tight junctions and increase paracellular permeability. We examined the effects of elevated acetaldehyde within the gastrointestinal tract on the permeability and bioavailability of hydrophilic markers and drug molecules of variable molecular weight and geometry. In vitro permeability was measured unidirectionally in Caco-2 and MDCKII cell models in the presence of acetaldehyde, ethanol, or disulfiram, an aldehyde dehydrogenase inhibitor, which causes acetaldehyde formation when coadministered with ethanol in vivo. Acetaldehyde significantly lowered transepithelial resistance in cell monolayers and increased permeability of the low-molecular-weight markers, mannitol and sucrose; however, permeability of high-molecular-weight markers, polyethylene glycol and inulin, was not affected. In vivo permeability was assessed in male Sprague-Dawley rats treated for 6 days with ethanol, disulfiram, or saline alone or in combination. Bioavailability of naproxen was not affected by any treatment, whereas that of paclitaxel was increased upon acetaldehyde exposure. Although disulfiram has been shown to inhibit multidrug resistance-1 P-glycoprotein (P-gp) in vitro, our data demonstrate that the known P-gp substrate paclitaxel is not affected by coadministration of disulfiram. In conclusion, we demonstrate that acetaldehyde significantly modulates tight junctions and paracellular permeability in vitro as well as the oral bioavailability of low-molecular-weight hydrophilic probes and therapeutic molecules in vivo even when these molecules are substrates for efflux transporters. These studies emphasize the significance of ethanol metabolism and drug interactions outside of the liver.

Surface-subsurface turbulent interaction at the interface of a permeable bed: influence of the wall permeability

NASA Astrophysics Data System (ADS)

Kim, T.; Blois, G.; Best, J.; Christensen, K. T.

2017-12-01

Coarse-gravel river beds possess a high degree of permeability. Flow interactions between surface and subsurface flow across the bed interface is key to a number of natural processes occurring in the hyporheic zone. In fact, it is increasingly recognized that these interactions drive mass, momentum and energy transport across the interface, and consequently control biochemical processes as well as stability of sediments. The current study explores the role of the wall permeability in surface and subsurface flow interaction under controlled experimental conditions on a physical model of a gravel bed. The present wall model was constructed by five layers of cubically arranged spheres (d=25.4mm, where d is a diameter) providing 48% of porosity. Surface topography was removed by cutting half of a diameter on the top layer of spheres to render the flow surface smooth and highlight the impact of the permeability on the overlying flow. An impermeable smooth wall was also considered as a baseline of comparison for the permeable wall flow. To obtain basic flow statistics, low-frame-rate high-resolution PIV measurements were performed first in the streamwise-wall-normal (x-y) plane and refractive-index matching was employed to optically access the flow within the permeable wall. Time-resolved PIV experiments in the same facility were followed to investigate the flow interaction across the wall interface in sptaio-temporal domain. In this paper, a detailed analysis of the first and second order velocity statistics as well as the amplitude modulation for the flow overlying the permeable smooth wall will be presented.

Fluid flow simulation and permeability computation in deformed porous carbonate grainstones

NASA Astrophysics Data System (ADS)

Zambrano, Miller; Tondi, Emanuele; Mancini, Lucia; Lanzafame, Gabriele; Trias, F. Xavier; Arzilli, Fabio; Materazzi, Marco; Torrieri, Stefano

2018-05-01

In deformed porous carbonates, the architecture of the pore network may be modified by deformation or diagenetic processes altering the permeability with respect to the pristine rock. The effects of the pore texture and morphology on permeability in porous rocks have been widely investigated due to the importance during the evaluation of geofluid reservoirs. In this study, these effects are assessed by combining synchrotron X-ray computed microtomography (SR micro-CT) and computational fluid dynamics. The studied samples pertain to deformed porous carbonate grainstones highly affected by deformation bands (DBs) exposed in Northwestern Sicily and Abruzzo regions, Italy. The high-resolution SR micro-CT images of the samples, acquired at the SYRMEP beamline of the Elettra - Sincrotrone Trieste laboratory (Italy), were used for simulating a pressure-driven flow by using the lattice-Boltzmann method (LBM). For the experiments, a multiple relaxation time (MRT) model with the D3Q19 scheme was used to avoid viscosity-dependent results of permeability. The permeability was calculated using Darcy's law once steady conditions were reached. After the simulations, the pore-network properties (effective porosity, specific surface area, and geometrical tortuosity) were calculated using 3D images of the velocity fields. These images were segmented considering a velocity threshold value higher than zero. The study showed that DBs may generate significant heterogeneity and anisotropy of the permeability of the evaluated rock samples. Cataclasis and cementation process taking place within the DBs reduce the effective porosity and therefore the permeability. Contrary to this, pressure dissolution and faulting may generate connected channels which contribute to the permeability only parallel to the DB.

21 CFR 876.5860 - High permeability hemodialysis system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Water Purification Components and Systems for Hemodialysis,” and (5) “Guidance for Hemodialyzer Reuse... hemodiafiltration. Using a hemodialyzer with a semipermeable membrane that is more permeable to water than the...

21 CFR 876.5860 - High permeability hemodialysis system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Water Purification Components and Systems for Hemodialysis,” and (5) “Guidance for Hemodialyzer Reuse... hemodiafiltration. Using a hemodialyzer with a semipermeable membrane that is more permeable to water than the...

21 CFR 876.5860 - High permeability hemodialysis system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Water Purification Components and Systems for Hemodialysis,” and (5) “Guidance for Hemodialyzer Reuse... hemodiafiltration. Using a hemodialyzer with a semipermeable membrane that is more permeable to water than the...

21 CFR 876.5860 - High permeability hemodialysis system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Water Purification Components and Systems for Hemodialysis,” and (5) “Guidance for Hemodialyzer Reuse... hemodiafiltration. Using a hemodialyzer with a semipermeable membrane that is more permeable to water than the...

21 CFR 876.5860 - High permeability hemodialysis system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Water Purification Components and Systems for Hemodialysis,” and (5) “Guidance for Hemodialyzer Reuse... hemodiafiltration. Using a hemodialyzer with a semipermeable membrane that is more permeable to water than the...

pH Dependent but not P-gp Dependent Bidirectional Transport Study of S-propranolol: The Importance of Passive Diffusion.

PubMed

Zheng, Yi; Benet, Leslie Z; Okochi, Hideaki; Chen, Xijing

2015-08-01

Recent controversial publications, citing studies purporting to show that P-gp mediates the transport of propranolol, proposed that passive biological membrane transport is negligible. Based on the BDDCS, the extensively metabolized-highly permeable-highly soluble BDDCS class 1 drug, propranolol, shows a high passive permeability at concentrations unrestricted by solubility that can overwhelm any potential transporter effects. Here we reinvestigate the effects of passive diffusion and carrier-mediated transport on S-propranolol. Bidirectional permeability and inhibition of efflux transport studies were carried out in MDCK, MDCK-MDR1 and Caco-2 cell lines at different concentrations. Transcellular permeability studies were conducted at different apical pHs in the rat jejunum Ussing chamber model and PAMPA system. S-propranolol exhibited efflux ratios lower than 1 in MDCK, MDCK-MDR1 and Caco-2 cells. No significant differences of Papp, B->A in the presence and absence of the efflux inhibitor GG918 were observed. However, an efflux ratio of 3.63 was found at apical pH 6.5 with significant decrease in Papp, A->B and increase in Papp, B->A compared to apical pH 7.4 in Caco-2 cell lines. The pH dependent permeability was confirmed in the Ussing chamber model. S-propranolol flux was unchanged during inhibition by verapamil and rifampin. Furthermore, pH dependent permeability was also observed in the PAMPA system. S-propranolol does not exhibit active transport as proposed previously. The "false" positive efflux ratio can be explained by the pH partition theory. As expected, passive diffusion, but not active transport, plays the primary role in the permeability of the BDDCS class 1 drug propranolol.

pH dependent but not P-gp dependent bidirectional transport study of S-propranolol: the importance of passive diffusion

PubMed Central

Zheng, Yi; Benet, Leslie Z.; Okochi, Hideaki; Chen, Xijing

2016-01-01

Purpose Recent controversial publications, citing studies purporting to show that P-gp mediates the transport of propranolol, proposed that passive biological membrane transport is negligible. Based on the BDDCS, the extensively metabolized-highly permeable-highly soluble BDDCS class 1 drug, propranolol, shows a high passive permeability at concentrations unrestricted by solubility that can overwhelm any potential transporter effects. Here we reinvestigate the effects of passive diffusion and carrier-mediated transport on S-propranolol. Methods Bidirectional permeability and inhibition of efflux transport studies were carried out in MDCK, MDCK-MDR1 and Caco-2 cell lines at different concentrations. Transcellular permeability studies were conducted at different apical pHs in the rat jejunum Ussing chamber model and PAMPA system. Results S-propranolol exhibited efflux ratios lower than 1 in MDCK, MDCK-MDR1 and Caco-2 cells. No significant differences of Papp, B->A in the presence and absence of the efflux inhibitor GG918 were observed. However, an efflux ratio of 3.63 was found at apical pH 6.5 with significant decrease in Papp, A->B and increase in Papp, B->A compared to apical pH 7.4 in Caco-2 cell lines. The pH dependent permeability was confirmed in the Ussing chamber model. S-propranolol flux was unchanged during inhibition by verapamil and rifampin. Furthermore, pH dependent permeability was also observed in the PAMPA system. Conclusions S-propranolol does not exhibit active transport as proposed previously. The "false" positive efflux ratio can be explained by the pH partition theory. As expected, passive diffusion, but not active transport, plays the primary role in the permeability of the BDDCS class 1 drug propranolol. PMID:25690341

Microfracture development and foam collapse during lava dome growth

NASA Astrophysics Data System (ADS)

Ashwell, P.; Kendrick, J. E.; Lavallee, Y.; kennedy, B.; Hess, K.; Cole, J. W.; Dingwell, D. B.

2012-12-01

The ability of a volcano to degas effectively is regulated by the collapse of the foam during lava dome growth. As a lava dome extrudes and cools, it will begin to collapse under its own weight, leading to the closure of bubbles and the eventual blockage of the permeable foam network. A reduction in the lavas permeability hinders gas movement and increases internal bubble pressure, which may eventually lead to failure of the bubble walls, and ultimately to explosive fragmentation of the dome. However, the behaviour of lava dome material under compression is poorly understood. Here we present the results of low-load, uniaxial, high temperature (850oC) compression experiments on glassy, rhyolitic dome material from Ngongotaha (~200ka, following collapse of Rotorua Caldera) and Tarawera (1314AD, from dome collapse generated block and ash flow) domes in New Zealand. The development of textures and microstructures was tracked using neutron computed tomography at incremental stages of strain. Porosity and permeability measurements, using pycnometry and gas permeability, before and after each experiment quantified the evolution of the permeable bubble network. Our results show that uniaxial compression of vesicular lava leads to a systematic reduction of porosity on a timescale comparable to volcanic eruptions (hours - days). The closure of bubbles naturally decreases permeability parallel and perpendicular to the applied load, and at high strains fractures begin to initiate in phenocrysts and propagate vertically into the glass. These microfractures result in localised increases in permeability. Crystallinity and initial vesicularity of each sample affects the rate of bubble collapse and the evolution of permeability. The most highly compressed samples (60%) show textures similar to samples collected from the centre of Tarawera Dome, thought to have suffered from collapse shortly after dome emplacement. However, structures and porosities in the deformed Ngongotaha samples differ from the natural collapsed dome material. The interior of Ngongotaha Dome shows complex deformed flow banding, indicating that shearing during emplacement was a major component during collapse of the permeable foam. Understanding the development of the porous permeable network during lava dome growth is key to predicting the behaviour of an erupting volcano, and the assessing the likelihood of pressure build-up leading to a catastrophic explosive eruption.

Hydrogeology and geochemistry of low-permeability oil-shales - Case study from HaShfela sub-basin, Israel

NASA Astrophysics Data System (ADS)

Burg, Avihu; Gersman, Ronen

2016-09-01

Low permeability rocks are of great importance given their potential role in protecting underlying aquifers from surface and buried contaminants. Nevertheless, only limited data for these rocks is available. New appraisal wells drilled into the oil shale unit (OSU) of the Mt. Scopus Group in the HaShfela sub-basin, Central Israel, provided a one-time opportunity for detailed study of the hydrogeology and geochemistry of this very low permeability unit. Methods used include: slug tests, electrical logs, televiewer imaging, porosity and permeability measurements on core samples, chemical analyses of the rock column and groundwater analyses. Slug tests yielded primary indication to the low permeability of the OSU despite its high porosity (30-40%). Hydraulic conductivities as low as 10-10-10-12 m/s were calculated, using both the Hvorslev and Cooper-Bredehoeft-Papadopulos decoding methods. These low conductivities were confirmed by direct measurements of permeability in cores, and from calculations based on the Kozeny-Carman approach. Storativity was found to be 1 · 10-6 and specific storage - 3.8 · 10-9 m-1. Nevertheless, the very limited water flow in the OSU is argued to be driven gravitationally. The extremely slow recovery rates as well as the independent recovery of two adjacent wells, despite their initial large head difference of 214 m, indicate that the natural fractures are tight and are impermeable due to the confining stress at depth. Laboratory measured permeability is similar or even higher than the field-measured values, thereby confirming that fractures and bedding planes do not form continuous flow paths. The vertical permeability along the OSU is highly variable, implying hydraulic stratification and extremely low vertical hydraulic conductivity. The high salinity of the groundwater (6300-8000 mgCl/L) within the OSU and its chemical and isotopic compositions are explained by the limited water flow, suggesting long residence time of the water, prolonged water-rock interaction and mixing with ancient trapped salty water. The current study demonstrates that targeted and detailed research of low permeability rocks can produce reliable hydraulic parameters using slug tests and accompanying methods. The data produced is of upmost importance for quantitative risk evaluations such as models for waste burial in low permeability units.

Urban evaporation rates for water-permeable pavements.

PubMed

Starke, P; Göbel, P; Coldewey, W G

2010-01-01

In urban areas the natural water balance is disturbed. Infiltration and evaporation are reduced, resulting in a high surface runoff and a typical city climate, which can lead to floods and damages. Water-permeable pavements have a high infiltration rate that reduces surface runoff by increasing the groundwater recharge. The high water retention capacity of the street body of up to 51 l/m(2) and its connection via pores to the surface lead to higher evaporation rates than impermeable surfaces. A comparison of these two kinds of pavements shows a 16% increase in evaporation levels of water-permeable pavements. Furthermore, the evaporation from impermeable pavements is linked directly to rain events due to fast-drying surfaces. Water-permeable pavements show a more evenly distributed evaporation after a rain event. Cooling effects by evaporative heat loss can improve the city climate even several days after rain events. On a large scale use, uncomfortable weather like sultriness or dry heat can be prevented and the urban water balance can be attenuated towards the natural.

Hydrogen transport membranes

DOEpatents

Mundschau, Michael V.

2005-05-31

Composite hydrogen transport membranes, which are used for extraction of hydrogen from gas mixtures are provided. Methods are described for supporting metals and metal alloys which have high hydrogen permeability, but which are either too thin to be self supporting, too weak to resist differential pressures across the membrane, or which become embrittled by hydrogen. Support materials are chosen to be lattice matched to the metals and metal alloys. Preferred metals with high permeability for hydrogen include vanadium, niobium, tantalum, zirconium, palladium, and alloys thereof. Hydrogen-permeable membranes include those in which the pores of a porous support matrix are blocked by hydrogen-permeable metals and metal alloys, those in which the pores of a porous metal matrix are blocked with materials which make the membrane impervious to gases other than hydrogen, and cermets fabricated by sintering powders of metals with powders of lattice-matched ceramic.

Permeability of compacting porous lavas

NASA Astrophysics Data System (ADS)

Ashwell, P. A.; Kendrick, J. E.; Lavallée, Y.; Kennedy, B. M.; Hess, K.-U.; von Aulock, F. W.; Wadsworth, F. B.; Vasseur, J.; Dingwell, D. B.

2015-03-01

The highly transient nature of outgassing commonly observed at volcanoes is in part controlled by the permeability of lava domes and shallow conduits. Lava domes generally consist of a porous outer carapace surrounding a denser lava core with internal shear zones of variable porosity. Here we examine densification using uniaxial compression experiments on variably crystalline and porous rhyolitic dome lavas from the Taupo Volcanic Zone. Experiments were conducted at 900°C and an applied stress of 3 MPa to 60% strain, while monitoring acoustic emissions to track cracking. The evolution of the porous network was assessed via X-ray computed tomography, He-pycnometry, and relative gas permeability. High starting connected porosities led to low apparent viscosities and high strain rates, initially accompanied by abundant acoustic emissions. As compaction ensued, the lavas evolved; apparent viscosity increased and strain rate decreased due to strain hardening of the suspensions. Permeability fluctuations resulted from the interplay between viscous flow and brittle failure. Where phenocrysts were abundant, cracks had limited spatial extent, and pore closure decreased axial and radial permeability proportionally, maintaining the initial anisotropy. In crystal-poor lavas, axial cracks had a more profound effect, and permeability anisotropy switched to favor axial flow. Irrespective of porosity, both crystalline samples compacted to a threshold minimum porosity of 17-19%, whereas the crystal-poor sample did not achieve its compaction limit. This indicates that unconfined loading of porous dome lavas does not necessarily form an impermeable plug and may be hindered, in part by the presence of crystals.

Magnetic Shielding Design for Coupler of Wireless Electric Vehicle Charging Using Finite Element Analysis

NASA Astrophysics Data System (ADS)

Zhao, W. N.; Yang, X. J.; Yao, C.; Ma, D. G.; Tang, H. J.

2017-10-01

Inductive power transfer (IPT) is a practical and preferable method for wireless electric vehicle (EV) charging which proved to be safe, convenient and reliable. Due to the air gap between the magnetic coupler, the magnetic field coupling decreases and the magnetic leakage increases significantly compared to traditional transformer, and this may lead to the magnetic flux density around the coupler more than the safety limit for human. So magnetic shielding should be adding to the winding made from litz wire to enhance the magnetic field coupling effect in the working area and reduce magnetic field strength in non-working area. Magnetic shielding can be achieved by adding high-permeability material or high-conductivity material. For high-permeability material its magnetic reluctance is much lower than the surrounding air medium so most of the magnetic line goes through the high-permeability material rather than surrounding air. For high-conductivity material the eddy current in the material can produce reverse magnetic field to achieve magnetic shielding. This paper studies the effect of the two types of shielding material on coupler for wireless EV charging and designs combination shielding made from high-permeability material and high-conductivity material. The investigation of the paper is done with the help of finite element analysis.

Magnetic field extraction of trap-based electron beams using a high-permeability grid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hurst, N. C.; Danielson, J. R.; Surko, C. M., E-mail: csurko@physics.ucsd.edu

2015-07-15

A method to form high quality electrostatically guided lepton beams is explored. Test electron beams are extracted from tailored plasmas confined in a Penning-Malmberg trap. The particles are then extracted from the confining axial magnetic field by passing them through a high magnetic permeability grid with radial tines (a so-called “magnetic spider”). An Einzel lens is used to focus and analyze the beam properties. Numerical simulations are used to model non-adiabatic effects due to the spider, and the predictions are compared with the experimental results. Improvements in beam quality are discussed relative to the use of a hole in amore » high permeability shield (i.e., in lieu of the spider), and areas for further improvement are described.« less

Integration of Multi-Tension Permeametry and Photogrammetric Textural Segmentation for Estimating Directional Permeability

DTIC Science & Technology

2010-04-01

this heterogeneity, for the purpose of predicting water flow and reactive transport behavior at the field scale, has proven quite difficult. This...potential (soil water pressure) at the outlet and at offset points in response injections at different inlet pressure heads. 13 Task 2: Development...preferential pathways (Wu et al., 1993). A viable solution to this problem is to supply water under tension using an inflatable borehole

Discontinuities in effective permeability due to fracture percolation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyman, Jeffrey De'Haven; Karra, Satish; Carey, James William

Motivated by a triaxial coreflood experiment with a sample of Utica shale where an abrupt jump in permeability was observed, possibly due to the creation of a percolating fracture network through the sample, we perform numerical simulations based on the experiment to characterize how the effective permeability of otherwise low-permeability porous media depends on fracture formation, connectivity, and the contrast between the fracture and matrix permeabilities. While a change in effective permeability due to fracture formation is expected, the dependence of its magnitude upon the contrast between the matrix permeability and fracture permeability and the fracture network structure is poorlymore » characterized. We use two different high-fidelity fracture network models to characterize how effective permeability changes as percolation occurs. The first is a dynamic two-dimensional fracture propagation model designed to mimic the laboratory settings of the experiment. The second is a static three-dimensional discrete fracture network (DFN) model, whose fracture and network statistics are based on the fractured sample of Utica shale. Once the network connects the inflow and outflow boundaries, the effective permeability increases non-linearly with network density. In most networks considered, a jump in the effective permeability was observed when the embedded fracture network percolated. We characterize how the magnitude of the jump, should it occur, depends on the contrast between the fracture and matrix permeabilities. For small contrasts between the matrix and fracture permeabilities the change is insignificant. However, for larger contrasts, there is a substantial jump whose magnitude depends non-linearly on the difference between matrix and fracture permeabilities. A power-law relationship between the size of the jump and the difference between the matrix and fracture permeabilities is observed. In conclusion, the presented results underscore the importance of fracture network topology on the upscaled properties of the porous medium in which it is embedded.« less

Discontinuities in effective permeability due to fracture percolation

DOE PAGES

Hyman, Jeffrey De'Haven; Karra, Satish; Carey, James William; ...

2018-01-31

Motivated by a triaxial coreflood experiment with a sample of Utica shale where an abrupt jump in permeability was observed, possibly due to the creation of a percolating fracture network through the sample, we perform numerical simulations based on the experiment to characterize how the effective permeability of otherwise low-permeability porous media depends on fracture formation, connectivity, and the contrast between the fracture and matrix permeabilities. While a change in effective permeability due to fracture formation is expected, the dependence of its magnitude upon the contrast between the matrix permeability and fracture permeability and the fracture network structure is poorlymore » characterized. We use two different high-fidelity fracture network models to characterize how effective permeability changes as percolation occurs. The first is a dynamic two-dimensional fracture propagation model designed to mimic the laboratory settings of the experiment. The second is a static three-dimensional discrete fracture network (DFN) model, whose fracture and network statistics are based on the fractured sample of Utica shale. Once the network connects the inflow and outflow boundaries, the effective permeability increases non-linearly with network density. In most networks considered, a jump in the effective permeability was observed when the embedded fracture network percolated. We characterize how the magnitude of the jump, should it occur, depends on the contrast between the fracture and matrix permeabilities. For small contrasts between the matrix and fracture permeabilities the change is insignificant. However, for larger contrasts, there is a substantial jump whose magnitude depends non-linearly on the difference between matrix and fracture permeabilities. A power-law relationship between the size of the jump and the difference between the matrix and fracture permeabilities is observed. In conclusion, the presented results underscore the importance of fracture network topology on the upscaled properties of the porous medium in which it is embedded.« less

Regulation of Sodium Transport in the Inner Ear

PubMed Central

Kim, Sung Huhn; Marcus, Daniel C.

2011-01-01

Na+ concentrations in endolymph must be controlled to maintain hair cell function since the transduction channels of hair cells are cation-permeable, but not K+-selective. Flooding or fluctuations of the hair cell cytosol with Na+ would be expected to lead to cellular dysfunction, hearing loss and vertigo. This review briefly describes cellular mechanisms known to be responsible for Na+homeostasis in each compartment of the inner ear, including the cochlea, saccule, semicircular canals and endolymphatic sac. The influx of Na+into endolymph of each of the organs is likely via passive diffusion, but these pathways have not yet been identified or characterized. Na+ absorption is controlled by gate -keeper channels in the apical (endolymphatic) membrane of the transporting cells. Highly Na+-selective epithelial sodium channels (ENaC) control absorption by Reissner’s membrane, saccular extramacular epithelium, semicircular canal duct epithelium and endolymphatic sac. ENaC activity is controlled by a number of signal pathways, but most notably by genomic regulation of channel numbers in the membrane via glucocorticoid signaling. Nonselective cation channels in the apical membrane of outer sulcus epithelial cells and vestibular transitional cells mediate Na+ and parasensory K+ absorption. The K+-mediated transduction current in hair cells is also accompanied by a Na+ flux since the transduction channels are nonselective cation channels. Cation absorption by all of these cells is regulated by extracellular ATP via apical nonselective cation channels (P2X receptors). The heterogeneous population of epithelial cells in the endolymphatic sac is thought to have multiple absorptive pathways for Na+ with regulatory pathways that include glucocorticoids and purinergic agonists. PMID:21620939

Gas Permeable Chemochromic Compositions for Hydrogen Sensing

NASA Technical Reports Server (NTRS)

Mohajeri, Nahid (Inventor); Muradov, Nazim (Inventor); Tabatabaie-Raissi, Ali (Inventor); Bokerman, Gary (Inventor)

2013-01-01

A (H2) sensor composition includes a gas permeable matrix material intermixed and encapsulating at least one chemochromic pigment. The chemochromic pigment produces a detectable change in color of the overall sensor composition in the presence of H2 gas. The matrix material provides high H2 permeability, which permits fast permeation of H2 gas. In one embodiment, the chemochromic pigment comprises PdO/TiO2. The sensor can be embodied as a two layer structure with the gas permeable matrix material intermixed with the chemochromic pigment in one layer and a second layer which provides a support or overcoat layer.

Submarine slope failures due to pipe structure formation.

PubMed

Elger, Judith; Berndt, Christian; Rüpke, Lars; Krastel, Sebastian; Gross, Felix; Geissler, Wolfram H

2018-02-19

There is a strong spatial correlation between submarine slope failures and the occurrence of gas hydrates. This has been attributed to the dynamic nature of gas hydrate systems and the potential reduction of slope stability due to bottom water warming or sea level drop. However, 30 years of research into this process found no solid supporting evidence. Here we present new reflection seismic data from the Arctic Ocean and numerical modelling results supporting a different link between hydrates and slope stability. Hydrates reduce sediment permeability and cause build-up of overpressure at the base of the gas hydrate stability zone. Resulting hydro-fracturing forms pipe structures as pathways for overpressured fluids to migrate upward. Where these pipe structures reach shallow permeable beds, this overpressure transfers laterally and destabilises the slope. This process reconciles the spatial correlation of submarine landslides and gas hydrate, and it is independent of environmental change and water depth.

Kinetic parameters of rubidium transport pathways are normal in cystic fibrosis red cells.

PubMed

Joiner, C H

1988-10-01

The abnormalities in ion transport in cystic fibrosis (CF) respiratory and sweat duct epithelia have prompted studies of ion permeability in CF red blood cells (RBC) although previous reports have been contradictory. In this study, the kinetic characteristics of the three major cation transport systems in RBC were evaluated by measuring rubidium (Rb) uptake at various external Rb concentrations. The maximal velocity and affinity for external Rb (K1/2) of the NaK pump were normal in CF RBC, as were the maximal velocity and Km for Rb of the NaK cotransport system. Residual (ouabain and bumetanide insensitive) Rb uptake, and steady state RBC Na and K contents were also normal. These data indicate the NaK pump and cotransport system do not exhibit primary or secondary perturbations in CF RBC, and suggest that the noncarrier-mediated membrane permeability to cations is also normal in these cells.

Regulation of Endothelial Barrier Function by Cyclic Nucleotides: The Role of Phosphodiesterases

PubMed Central

Surapisitchat, James

2014-01-01

The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction. PMID:21695641

Regulation of endothelial barrier function by cyclic nucleotides: the role of phosphodiesterases.

PubMed

Surapisitchat, James; Beavo, Joseph A

2011-01-01

The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction.

Effect of permeability enhancers on paracellular permeability of acyclovir.

PubMed

Ates, Muge; Kaynak, Mustafa Sinan; Sahin, Selma

2016-06-01

According to Biopharmaceutics Classification System (BCS), acyclovir is a class III (high solubility, low permeability) compound, and it is transported through paracellular route by passive diffusion. The aim of this study was to investigate the effect of various pharmaceutical excipients on the intestinal permeability of acyclovir. The single-pass in-situ intestinal perfusion (SPIP) method was used to estimate the permeability values of acyclovir and metoprolol across different intestinal segments (jejunum, ileum and colon). Permeability coefficient (Peff ) of acyclovir was determined in the absence and presence of a permeation enhancer such as dimethyl β-cyclodextrin (DM-β-CD), sodium lauryl sulfate (SLS), sodium caprate (Cap-Na) and chitosan chloride. All enhancers increased the permeability of paracellularly transported acyclovir. Although Cap-Na has the highest permeability-enhancing effect in all segments, permeation-enhancing effect of chitosan and SLS was only significant in ileum. On the other hand, DM-β-CD slightly decreased the permeability in all intestinal segments. These findings have potential implication concerning the enhancement of absorption of paracellularly transported compounds with limited oral bioavailability. In the case of acyclovir, Cap-Na either alone or in combination with SLS or chitosan has the potential to improve its absorption and bioavailability and has yet to be explored. © 2016 Royal Pharmaceutical Society.

Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice.

PubMed

Bagarolli, Renata A; Tobar, Natália; Oliveira, Alexandre G; Araújo, Tiago G; Carvalho, Bruno M; Rocha, Guilherme Z; Vecina, Juliana F; Calisto, Kelly; Guadagnini, Dioze; Prada, Patrícia O; Santos, Andrey; Saad, Sara T O; Saad, Mario J A

2017-12-01

Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

The site-scale saturated zone flow model for Yucca Mountain: Calibration of different conceptual models and their impact on flow paths

USGS Publications Warehouse

Zyvoloski, G.; Kwicklis, E.; Eddebbarh, A.-A.; Arnold, B.; Faunt, C.; Robinson, B.A.

2003-01-01

This paper presents several different conceptual models of the Large Hydraulic Gradient (LHG) region north of Yucca Mountain and describes the impact of those models on groundwater flow near the potential high-level repository site. The results are based on a numerical model of site-scale saturated zone beneath Yucca Mountain. This model is used for performance assessment predictions of radionuclide transport and to guide future data collection and modeling activities. The numerical model is calibrated by matching available water level measurements using parameter estimation techniques, along with more informal comparisons of the model to hydrologic and geochemical information. The model software (hydrologic simulation code FEHM and parameter estimation software PEST) and model setup allows for efficient calibration of multiple conceptual models. Until now, the Large Hydraulic Gradient has been simulated using a low-permeability, east-west oriented feature, even though direct evidence for this feature is lacking. In addition to this model, we investigate and calibrate three additional conceptual models of the Large Hydraulic Gradient, all of which are based on a presumed zone of hydrothermal chemical alteration north of Yucca Mountain. After examining the heads and permeabilities obtained from the calibrated models, we present particle pathways from the potential repository that record differences in the predicted groundwater flow regime. The results show that Large Hydraulic Gradient can be represented with the alternate conceptual models that include the hydrothermally altered zone. The predicted pathways are mildly sensitive to the choice of the conceptual model and more sensitive to the quality of calibration in the vicinity on the repository. These differences are most likely due to different degrees of fit of model to data, and do not represent important differences in hydrologic conditions for the different conceptual models. ?? 2002 Elsevier Science B.V. All rights reserved.

In Vitro Plasma Stability, Permeability and Solubility of Mercaptoacetamide Histone Deacetylase Inhibitors

PubMed Central

Konsoula, Roula; Jung, Mira

2008-01-01

Histone deacetylase inhibitors (HDACIs) are emerging as a new class of therapeutic agents with potent antitumor activities in a broad spectrum of human cancers. In this study, the in vitro plasma stability, permeability, solubility, and lipophilicity (logD) of two mercaptoacetamide-based HDACIs (coded as W2 and S2) were evaluated and compared to Vorinostat (SAHA). The results demonstrated that the compounds manifested high solubility in HCl (pH 1.2) but lower in PBS (pH 7.4) than SAHA. Moreover, mercaptoacetamide-based HDACIs exhibited higher lipophilicity values compared to SAHA. The permeability of these compounds was evaluated using the Caco-2 cell monolayer as a model of the intestinal mucosa. The Caco-2 studies revealed that the compounds S2 and W2 are highly permeable with apparent permeability coefficients (Papp) in the apical to basolateral direction of 7.33 × 10−6 and 15.0 × 10−6 cm/s, respectively. The in vitro stability was determined in human, mouse, porcine and rat plasma. Data showed that the compound W2 is more stable in human and rat plasma and the S2 is more stable in all plasma species than SAHA. Taken together, these results indicate that the mercaptoacetamide-based HDACIs possess favorable solubility, lipophilicity, permeability and plasma stability features. PMID:18562136

Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3).

PubMed

Stavchansky, Salomon

2008-06-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA-BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility-Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.

Transport pathways and enhancement mechanisms within localized and non-localized transport regions in skin treated with low-frequency sonophoresis and sodium lauryl sulfate.

PubMed

Polat, Baris E; Figueroa, Pedro L; Blankschtein, Daniel; Langer, Robert

2011-02-01

Recent advances in transdermal drug delivery utilizing low-frequency sonophoresis (LFS) and sodium lauryl sulfate (SLS) have revealed that skin permeability enhancement is not homogenous across the skin surface. Instead, highly perturbed skin regions, known as localized transport regions (LTRs), exist. Despite these findings, little research has been conducted to identify intrinsic properties and formation mechanisms of LTRs and the surrounding less-perturbed non-LTRs. By independently analyzing LTR, non-LTR, and total skin samples treated at multiple LFS frequencies, we found that the pore radii (r(pore)) within non-LTRs are frequency-independent, ranging from 18.2 to 18.5 Å, but significantly larger than r(pore) of native skin samples (13.6 Å). Conversely, r(pore) within LTRs increase significantly with decreasing frequency from 161 to 276 Å and to ∞ (>300 Å) for LFS/SLS-treated skin at 60, 40, and 20 kHz, respectively. Our findings suggest that different mechanisms contribute to skin permeability enhancement within each skin region. We propose that the enhancement mechanism within LTRs is the frequency-dependent process of cavitation-induced microjet collapse at the skin surface, whereas the increased r(pore) values in non-LTRs are likely due to SLS perturbation, with enhanced penetration of SLS into the skin resulting from the frequency-independent process of microstreaming. Copyright © 2010 Wiley-Liss, Inc.

Transport Pathways and Enhancement Mechanisms within Localized and Non-Localized Transport Regions in Skin Treated with Low-Frequency Sonophoresis and Sodium Lauryl Sulfate

PubMed Central

Polat, Baris E.; Figueroa, Pedro L.; Blankschtein, Daniel; Langer, Robert

2011-01-01

Recent advances in transdermal drug delivery utilizing low-frequency sonophoresis (LFS) and sodium lauryl sulfate (SLS) have revealed that skin permeability enhancement is not homogenous across the skin surface. Instead, highly perturbed skin regions, known as localized transport regions (LTRs), exist. Despite these findings, little research has been conducted to identify intrinsic properties and formation mechanisms of LTRs and the surrounding less-perturbed non-LTRs. By independently analyzing LTR, non-LTR, and total skin samples treated at multiple LFS frequencies, we found that the pore radii (rpore) within non-LTRs are frequency-independent, ranging from 18.2 – 18.5 Å, but significantly larger than rpore of native skin samples (13.6 Å). Conversely, rpore within LTRs increases significantly with decreasing frequency from 161 Å, to 276 Å, and to ∞ (>300Å) for LFS/SLS-treated skin at 60 kHz, 40 kHz, and 20 kHz, respectively. Our findings suggest that different mechanisms contribute to skin permeability enhancement within each skin region. We propose that the enhancement mechanism within LTRs is the frequency-dependent process of cavitation-induced microjet collapse at the skin surface, while the increased rpore values in non-LTRs are likely due to SLS perturbation, with enhanced penetration of SLS into the skin resulting from the frequency-independent process of microstreaming. PMID:20740667

Insulin-loaded pH-sensitive hyaluronic acid nanoparticles enhance transcellular delivery.

PubMed

Han, Lina; Zhao, Yuefang; Yin, Lifang; Li, Ruiming; Liang, Yang; Huang, Huan; Pan, Shirong; Wu, Chuanbin; Feng, Min

2012-09-01

In the present study, we developed novel insulin-loaded hyaluronic acid (HA) nanoparticles for insulin delivery. The insulin-loaded HA nanoparticles were prepared by reverse-emulsion-freeze-drying method. This method led to a homogenous population of small HA nanoparticles with average size of 182.2 nm and achieved high insulin entrapment efficiencies (approximately 95%). The pH-sensitive HA nanoparticles as an oral delivery carrier showed advantages in protecting insulin against the strongly acidic environment of the stomach, and not destroying the junction integrity of epithelial cells which promise long-term safety for chronic insulin treatment. The results of transport experiments suggested that insulin-loaded HA nanoparticles were transported across Caco-2 cell monolayers mainly via transcellular pathway and their apparent permeability coefficient from apical to basolateral had more than twofold increase compared with insulin solution. The efflux ratio of P (app) (B to A) to P (app) (A to B) less than 1 demonstrated that HA nanoparticle-mediated transport of insulin across Caco-2 cell monolayers underwent active transport. The results of permeability through the rat small intestine confirmed that HA nanoparticles significantly enhanced insulin transport through the duodenum and ileum. Diabetic rats treated with oral insulin-loaded HA nanoparticles also showed stronger hypoglycemic effects than insulin solution. Therefore, these HA nanoparticles could be a promising candidate for oral insulin delivery.

Are phloem sieve tubes leaky conduits supported by numerous aquaporins?

PubMed

Stanfield, Ryan C; Hacke, Uwe G; Laur, Joan

2017-05-01

Aquaporin membrane water channels have been previously identified in the phloem of angiosperms, but currently their cellular characterization is lacking, especially in tree species. Pinpointing the cellular location will help generate new hypotheses of how membrane water exchange facilitates sugar transport in plants. We studied histological sections of balsam poplar ( Populus balsamifera L.) in leaf, petiole, and stem organs. Immuno-labeling techniques were used to characterize the distribution of PIP1 and PIP2 subfamilies of aquaporins along the phloem pathway. Confocal and super resolution microscopy (3D-SIM) was used to identify the localization of aquaporins at the cellular level. Sieve tubes of the leaf lamina, petiole, and stem were labeled with antibodies directed at PIP1s and PIP2s. While PIP2s were mostly observed in the plasma membrane, PIP1s showed both an internal membrane and plasma membrane labeling pattern. The specificity and consistency of PIP2 labeling in sieve element plasma membranes points to high water exchange rates between sieve tubes and adjacent cells. The PIP1s may relocate between internal membranes and the plasma membrane to facilitate dynamic changes in membrane permeability of sieve elements in response to changing internal or environmental conditions. Aquaporin-mediated changes in membrane permeability of sieve tubes would also allow for some control of radial exchange of water between xylem and phloem. © 2017 Botanical Society of America.

Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.

PubMed

Roxas, Jennifer Lising; Viswanathan, V K

2018-03-25

The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

Highly predictive and interpretable models for PAMPA permeability.

PubMed

Sun, Hongmao; Nguyen, Kimloan; Kerns, Edward; Yan, Zhengyin; Yu, Kyeong Ri; Shah, Pranav; Jadhav, Ajit; Xu, Xin

2017-02-01

Cell membrane permeability is an important determinant for oral absorption and bioavailability of a drug molecule. An in silico model predicting drug permeability is described, which is built based on a large permeability dataset of 7488 compound entries or 5435 structurally unique molecules measured by the same lab using parallel artificial membrane permeability assay (PAMPA). On the basis of customized molecular descriptors, the support vector regression (SVR) model trained with 4071 compounds with quantitative data is able to predict the remaining 1364 compounds with the qualitative data with an area under the curve of receiver operating characteristic (AUC-ROC) of 0.90. The support vector classification (SVC) model trained with half of the whole dataset comprised of both the quantitative and the qualitative data produced accurate predictions to the remaining data with the AUC-ROC of 0.88. The results suggest that the developed SVR model is highly predictive and provides medicinal chemists a useful in silico tool to facilitate design and synthesis of novel compounds with optimal drug-like properties, and thus accelerate the lead optimization in drug discovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of Low fouling Polyethersulfone Membranes by Simultaneously Phase Separation and Redox Polymerization

NASA Astrophysics Data System (ADS)

Roihatin, A.; Susanto, H.

2017-05-01

This paper presents preparation of low fouling PES membranes by non solvent induced phase separation (NIPS) coupled with redox polymerization. The membrane characterization included water permeability, morphology structure (by SEM) and surface chemistry (by FTIR). Water permeability measurements showed thatthe membranes have water permeability within the range 10-50 L/h.m2.bar. Addition of PEG dan PEGMA intopolymer solution increased water permeability, whereas blending redox initiator and crosslinker, MBAA in polymer solution decreased water permeability. Surface morfology of membranes by SEM showed that unmodified PES membrane had smaller pore size than PEG or PEGMA modified PES membranes. Furthermore, PES-PEG or PES-PEGMA membranes modified by blending with redox initiator and MBAA as crosslinker showed smaller pore size than unmodified membrane. FTIR analysis showed that all membranes have typical spectraof PES polymer; however no additional peak was observed forthe membranes prepared with addition of PEG/PEGMA, initiator redox and also crosslinker. The addition of PEG/PEGMA, redox initiator and crosslinker resulted in membranes with high rejection and an acceptable flux as well as more stable due to relatively high fouling resistance.

Bayesian inference for heterogeneous caprock permeability based on above zone pressure monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Namhata, Argha; Small, Mitchell J.; Dilmore, Rober

The presence of faults/ fractures or highly permeable zones in the primary sealing caprock of a CO2 storage reservoir can result in leakage of CO2. Monitoring of leakage requires the capability to detect and resolve the onset, location, and volume of leakage in a systematic and timely manner. Pressure-based monitoring possesses such capabilities. This study demonstrates a basis for monitoring network design based on the characterization of CO2 leakage scenarios through an assessment of the integrity and permeability of the caprock inferred from above zone pressure measurements. Four representative heterogeneous fractured seal types are characterized to demonstrate seal permeability rangingmore » from highly permeable to impermeable. Based on Bayesian classification theory, the probability of each fractured caprock scenario given above zone pressure measurements with measurement error is inferred. The sensitivity to injection rate and caprock thickness is also evaluated and the probability of proper classification is calculated. The time required to distinguish between above zone pressure outcomes and the associated leakage scenarios is also computed.« less

Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis.

PubMed

Nilsson, Anna; Peric, Alexandra; Strimfors, Marie; Goodwin, Richard J A; Hayes, Martin A; Andrén, Per E; Hilgendorf, Constanze

2017-07-25

Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

Physiological barriers to the oral delivery of curcumin.

PubMed

Berginc, K; Trontelj, J; Basnet, N Skalko; Kristl, A

2012-06-01

Curcumin, a principal component from Curcuma longa, with antioxidant and anti-inflammatory activities was proposed as a potential candidate for the preventation and/or treatment of cancer and chronic diseases. However, curcumin could not achieve its expected therapeutic outcome in clinical trials due to its low solubility and poor bioavailability. The actual intestinal physiological barriers limiting curcumin absorption after oral administration have not been fully investigated. To identify the main barriers curtailing its absorption, in vitro permeability of curcumin and flux of its glucuronide were monitored in rat jejunum and Transwell grown Caco-2 cells. Curcumin was more permeable under acidic conditions, but the permeability was substantially below the permeability of highly permeable standards. Its efflux could not be inhibited by specific Pgp and MRP inhibitors. BCRP was found to participate in curcumin transport, but the Organic Anion Transporting Polypeptide (OATP) did not. The permeability of curcumin significantly increased when the structure of mucus was compromised. The inhibitor of curcumin metabolism, piperin, failed to act as a permeability enhancer. Piperin inhibited Pgp and MRP transporters and decreased the amount of glucuronide transported back into the intestine. Inclusion of piperin in curcumin-containing formulations is highly recommended as to inhibit curcumin glucuronidation and to increase the transport of formed glucuronides into the plasma, therefore increasing the probability of glucuronide distribution into target tissue and inter-convertion to curcumin. It would also be beneficial, if curcumin delivery systems could reversibly compromise the mucous integrity to minimize the non-specific binding of curcumin to its constituents.

Chemical Stress Cracking of Acrylic Fibers.

DTIC Science & Technology

1982-05-01

stress, high fiber permeability, moderate fibe orientation, and water- plasticization . The proposed mechanism for bond cleava e involves cyclization of...tensile stress, high fiber permeability, moderate fiber orientation, and water- plasticization . The proposed mechanism for bond cleavage involves...chemical composition, plasticization , and other factors. It will be shown that the etching behavior does not reflect underlying hetero- geneities in the

Complementary analyses of hollow cylindrical unioriented permanent magnet (HCM) with high permeability external layer

NASA Astrophysics Data System (ADS)

Lobo, Carlos M. S.; Tosin, Giancarlo; Baader, Johann E.; Colnago, Luiz A.

2017-10-01

In this article, several studies based on analytical expressions and computational simulations on Hollow Cylindrical Magnets with an external soft ferromagnetic material (HCM magnets) are presented. Electromagnetic configurations, as well as permanent-magnet-based structures, are studied in terms of magnetic field strength and homogeneity. Permanent-magnet-based structures are further analyzed in terms of the anisotropy of the magnetic permeability. It was found that the HCM magnets produce a highly homogeneous magnetic field as long as the magnetic material is isotropic. The dependency of the magnetic field strength and homogeneity in terms of the anisotropy of the magnetic permeability is also explored here. These magnets can potentially be used in medium-resolution NMR spectrometers and high-field NMR spectrometers.

Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design

PubMed Central

2012-01-01

PI3K, AKT, and mTOR are key kinases from PI3K signaling pathway being extensively pursued to treat a variety of cancers in oncology. To search for a structurally differentiated back-up candidate to PF-04691502, which is currently in phase I/II clinical trials for treating solid tumors, a lead optimization effort was carried out with a tricyclic imidazo[1,5]naphthyridine series. Integration of structure-based drug design and physical properties-based optimization yielded a potent and selective PI3K/mTOR dual kinase inhibitor PF-04979064. This manuscript discusses the lead optimization for the tricyclic series, which both improved the in vitro potency and addressed a number of ADMET issues including high metabolic clearance mediated by both P450 and aldehyde oxidase (AO), poor permeability, and poor solubility. An empirical scaling tool was developed to predict human clearance from in vitro human liver S9 assay data for tricyclic derivatives that were AO substrates. PMID:24900568

Role of calcium in phosphatidylserine externalisation in red blood cells from sickle cell patients.

PubMed

Weiss, Erwin; Rees, David Charles; Gibson, John Stanley

2011-01-01

Phosphatidylserine exposure occurs in red blood cells (RBCs) from sickle cell disease (SCD) patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates Ca(2+) entry, providing an obvious link with phosphatidylserine exposure. The role of Ca(2+) was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [Ca(2+)] was increased. This effect was inhibited by dipyridamole, intracellular Ca(2+) chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high K(+) saline. Ca(2+) levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with Ca(2+) entry through the deoxygenation-induced pathway (P(sickle)), activating the Gardos channel. [Ca(2+)] required for phosphatidylserine scrambling are in the range achievable in vivo.

Anti-inflammatory Mechanism of Geniposide: Inhibiting the Hyperpermeability of Fibroblast-Like Synoviocytes via the RhoA/p38MAPK/NF-κB/F-Actin Signal Pathway

PubMed Central

Deng, Ran; Li, Feng; Wu, Hong; Wang, Wen-yu; Dai, Li; Zhang, Zheng-rong; Fu, Jun

2018-01-01

Geniposide (GE) is the extraction and purification of iridoid glycosides from the Gardenia jasminoides Ellis, which is a promising anti-inflammatory drug, but its mechanism of actions on rheumatoid arthritis (RA) has not been clarified. This study investigated the molecular mechanism behind GE reduced the high permeability of fibroblast-like synoviocytes (FLSs) derived from SD rats with adjuvant arthritis (AA), with the aims of observing the action of GE in AA rats and exploring new therapeutic strategies for RA treatment. The CCK-8 method was used to detect FLSs proliferation. The pro-inflammatory cytokines levels and anti-inflammatory cytokines levels in FLSs were determined by ELISA kits. FLSs permeability assay was performed on Transwell. Immunofluorescence was used to assay the arrangement and morphology of F-actin. The expression of the key molecules related to FLSs permeability (RhoA, p-p38MAPK, NF-κB p-p65 and F-actin) was detected by western blotting. After treatment with lipopolysaccharide (LPS), the proliferation and the permeability of the cells increased significantly (all P < 0.05). The expression of RhoA, p-p38MAPK, NF-κB p-p65 and F-actin in FLSs was higher compared with the control group, and F-actin was redistributed, with the formation of additional stress fibers. But, these conditions were moderated after treatment with GE. We demonstrated that the treatment of different concentrations of GE (25, 50, and 100 μg/mL) had a significant inhibitory effect on the proliferation and permeability of FLSs in vitro. Furthermore, the levels of interleukin (IL)-1β and IL-17 secreted by FLSs were decreased in different doses of GE groups, and the levels of anti-inflammatory cytokines (IL-4, TGF-β1) were increased. Under treatment with GE, low expression of RhoA downregulated expression of p-p38MAPK, NF-κB p-p65, and F-actin while compared with control group, and restored the hyperpermeability of FLSs due to LPS treatment. Taken together, GE might play its anti-inflammatory and immunoregulatory effects via regulating the relative equilibrium of pro-inflammatory cytokines and anti-inflammatory cytokines. GE attenuated the hyperpermeability of FLSs. The down-regulation of the conduction of RhoA/p38MAPK/NF-κB/F-actin signal may play a critical role in the mechanisms of GE on RA. GE could be an effective therapeutic agent for the treatment of RA. PMID:29497378

An integrated workflow for stress and flow modelling using outcrop-derived discrete fracture networks

NASA Astrophysics Data System (ADS)

Bisdom, K.; Nick, H. M.; Bertotti, G.

2017-06-01

Fluid flow in naturally fractured reservoirs is often controlled by subseismic-scale fracture networks. Although the fracture network can be partly sampled in the direct vicinity of wells, the inter-well scale network is poorly constrained in fractured reservoir models. Outcrop analogues can provide data for populating domains of the reservoir model where no direct measurements are available. However, extracting relevant statistics from large outcrops representative of inter-well scale fracture networks remains challenging. Recent advances in outcrop imaging provide high-resolution datasets that can cover areas of several hundred by several hundred meters, i.e. the domain between adjacent wells, but even then, data from the high-resolution models is often upscaled to reservoir flow grids, resulting in loss of accuracy. We present a workflow that uses photorealistic georeferenced outcrop models to construct geomechanical and fluid flow models containing thousands of discrete fractures covering sufficiently large areas, that does not require upscaling to model permeability. This workflow seamlessly integrates geomechanical Finite Element models with flow models that take into account stress-sensitive fracture permeability and matrix flow to determine the full permeability tensor. The applicability of this workflow is illustrated using an outcropping carbonate pavement in the Potiguar basin in Brazil, from which 1082 fractures are digitised. The permeability tensor for a range of matrix permeabilities shows that conventional upscaling to effective grid properties leads to potential underestimation of the true permeability and the orientation of principal permeabilities. The presented workflow yields the full permeability tensor model of discrete fracture networks with stress-induced apertures, instead of relying on effective properties as most conventional flow models do.

Reactive transport under stress: Permeability evolution by chemo-mechanical deformation

NASA Astrophysics Data System (ADS)

Roded, R.; Holtzman, R.

2017-12-01

The transport of reactive fluids in porous media is important in many natural and engineering processes. Reaction with the solid matrix—e.g. dissolution—changes the transport properties, which in turn affect the rate of reagent transport and hence the reaction. The importance of this highly nonlinear problem has motivated intensive research. Specifically, there have been numerous studies concerning the permeability evolution, especially the process of "wormholing", where preferential dissolution of the most conductive regions leads to a runaway permeability increase. Much less attention, however, has been given to the effect of geomechanics; that is, how the fact that the medium is under stress changes the permeability evolution. Here, we present a novel, mechanistic pore-scale model, simulating the interplay between pore opening by matrix dissolution and pore closure by mechanical compaction, facilitated by weakening caused by the very same process of dissolution. We combine a pore network model of reactive transport with a block-spring model that captures the effect of geomechanics through the update of the network properties. Our simulations show that permeability enhancement is inhibited by stress concentration downstream, in the less dissolved (hence stiffer) regions. Higher stresses lead to stronger inhibition, in agreement with experiments. The effect of stress also depends on the Damkohler number (Da)—the ratio between the flow and the reaction rate. At rapid injection (small Da), where dissolution is relatively uniform, stress has a significant effect on permeability. At slower flow rates (high Da, wormholing regime), stress affects the permeability evolution mostly in early stages, with a much smaller effect on the injected volume required for a significant permeability increase (breakthrough) than at low Da. Interestingly, at higher Da, stress concentration downstream induced by the more heterogeneous dissolution leads to a more homogeneous reagent transport, promoting wormhole competition.

Unraveling the dynamics of magmatic CO2 degassing at Mammoth Mountain, California

NASA Astrophysics Data System (ADS)

Peiffer, Loïc; Wanner, Christoph; Lewicki, Jennifer L.

2018-02-01

The accumulation of magmatic CO2 beneath low-permeability barriers may lead to the formation of CO2-rich gas reservoirs within volcanic systems. Such accumulation is often evidenced by high surface CO2 emissions that fluctuate over time. The temporal variability in surface degassing is believed in part to reflect a complex interplay between deep magmatic degassing and the permeability of degassing pathways. A better understanding of the dynamics of CO2 degassing is required to improve monitoring and hazards mitigation in these systems. Owing to the availability of long-term records of CO2 emissions rates and seismicity, Mammoth Mountain in California constitutes an ideal site towards such predictive understanding. Mammoth Mountain is characterized by intense soil CO2 degassing (up to ∼1000 t d-1) and tree kill areas that resulted from leakage of CO2 from a CO2-rich gas reservoir located in the upper ∼4 km. The release of CO2-rich fluids from deeper basaltic intrusions towards the reservoir induces seismicity and potentially reactivates faults connecting the reservoir to the surface. While this conceptual model is well-accepted, there is still a debate whether temporally variable surface CO2 fluxes directly reflect degassing of intrusions or variations in fault permeability. Here, we report the first large-scale numerical model of fluid and heat transport for Mammoth Mountain. We discuss processes (i) leading to the initial formation of the CO2-rich gas reservoir prior to the occurrence of high surface CO2 degassing rates and (ii) controlling current CO2 degassing at the surface. Although the modeling settings are site-specific, the key mechanisms discussed in this study are likely at play at other volcanic systems hosting CO2-rich gas reservoirs. In particular, our model results illustrate the role of convection in stripping a CO2-rich gas phase from a rising hydrothermal fluid and leading to an accumulation of a large mass of CO2 (∼107-108 t) in a shallow gas reservoir. Moreover, we show that both, short-lived (months to years) and long-lived (hundreds of years) events of magmatic fluid injection can lead to critical pressures within the reservoir and potentially trigger fault reactivation. Our sensitivity analysis suggests that observed temporal fluctuations in surface degassing are only indirectly controlled by variations in magmatic degassing and are mainly the result of temporally variable fault permeability. Finally, we suggest that long-term CO2 emission monitoring, seismic tomography and coupled thermal-hydraulic-mechanical modeling are important for CO2-related hazard mitigation.

Net Intestinal Transport of Oxalate Reflects Passive Absorption and SLC26A6-mediated Secretion

PubMed Central

Knauf, Felix; Ko, Narae; Jiang, Zhirong; Robertson, William G.; Van Itallie, Christina M.; Anderson, James M.

2011-01-01

Mice lacking the oxalate transporter SLC26A6 develop hyperoxalemia, hyperoxaluria, and calcium-oxalate stones as a result of a defect in intestinal oxalate secretion, but what accounts for the absorptive oxalate flux remains unknown. We measured transepithelial absorption of [14C]oxalate simultaneously with the flux of [3H]mannitol, a marker of the paracellular pathway, across intestine from wild-type and Slc26a6-null mice. We used the anion transport inhibitor DIDS to investigate other members of the SLC26 family that may mediate transcellular oxalate absorption. Absorptive flux of oxalate in duodenum was similar to mannitol, insensitive to DIDS, and nonsaturable, indicating that it is predominantly passive and paracellular. In contrast, in wild-type mice, secretory flux of oxalate in duodenum exceeded that of mannitol, was sensitive to DIDS, and saturable, indicating transcellular secretion of oxalate. In Slc26a6-null mice, secretory flux of oxalate was similar to mannitol, and no net flux of oxalate occurred. Absorptive fluxes of both oxalate and mannitol varied in parallel in different segments of small and large intestine. In epithelial cell lines, modulation of the charge selectivity of the claudin-based pore pathway did not affect oxalate permeability, but knockdown of the tight-junction protein ZO-1 enhanced permeability to oxalate and mannitol in parallel. Moreover, formation of soluble complexes with cations did not affect oxalate absorption. In conclusion, absorptive oxalate flux occurs through the paracellular “leak” pathway, and net absorption of dietary oxalate depends on the relative balance between absorption and SLC26A6-dependent transcellular secretion. PMID:22021714

Leflunomide or A77 1726 protect from acetaminophen-induced cell injury through inhibition of JNK-mediated mitochondrial permeability transition in immortalized human hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latchoumycandane, Calivarathan; Seah, Quee Ming; Tan, Rachel C.H.

2006-11-15

Leflunomide, a disease-modifying anti-rheumatic drug, protects against T-cell-mediated liver injury by poorly understood mechanisms. The active metabolite of leflunomide, A77 1726 (teriflunomide) has been shown to inhibit stress-activated protein kinases (JNK pathway), which are key regulators of mitochondria-mediated cell death. Therefore, we hypothesized that leflunomide may protect from drugs that induce the mitochondrial permeability transition (mPT) by blocking the JNK signaling pathway. To this end, we exposed cultured immortalized human hepatocytes (HC-04) to the standard protoxicant drug acetaminophen (APAP), which induces CsA-sensitive mPT-mediated cell death. We determined the effects of leflunomide on the extent of APAP-induced hepatocyte injury and themore » upstream JNK-mediated mitochondrial signaling pathways. We found that leflunomide or A77 1726 concentration-dependently protected hepatocytes from APAP (1 mM)-induced mitochondrial permeabilization and lethal cell injury. This was not due to proximal inhibition of CYP-catalyzed APAP bioactivation to its thiol-reactive metabolite. Instead, we demonstrate that leflunomide (20 {mu}M) inhibited the APAP-induced early (3 h) activation (phosphorylation) of JNK1/2, thus inhibiting phosphorylation of the anti-apoptotic protein Bcl-2 and preventing P-Bcl-2-mediated induction of the mPT. This greatly attenuated mitochondrial cytochrome c release, which we used as a marker for mitochondrial permeabilization. The specific JNK2 inhibitor SP600125 similarly protected from APAP-induced cell death. In conclusion, these findings are consistent with our hypothesis that leflunomide protects from protoxicant-induced hepatocyte injury by inhibiting JNK signaling and preventing mPT induction.« less

Advanced glycation end‑products affect the cytoskeletal structure of rat glomerular endothelial cells via the Ras‑related C3 botulinum toxin substrate 1 signaling pathway.

PubMed

Lan, Lei; Han, Yongsheng; Ren, Wei; Jiang, Jielong; Wang, Peng; Hu, Zhao

2015-06-01

The present study aimed to determine the molecular mechanisms leading to the production of advanced glycation end‑products (AGEs) and their effect on the morphology and function of rat glomerular capillary endothelial cells (GECs). Primary rat GECs were treated with AGE‑modified human serum albumin (AGE‑HSA) and divided into groups according to AGE concentration and treatment time. The structure and distribution of cytoskeletal protein F‑actin and the cortical actin binding protein, cortactin, were analyzed using immunofluorescence and confocal microscopy. As the Ras‑related C3 botulinum toxin substrate 1 (Rac1) signaling pathway was previously identified to be involved in mediating the contraction of endothelial actin‑myosin activity, Rac1 was examined subsequent to treatment of the cells with the Rac1 agonist 2'‑O‑methyladenosine‑3',5'‑cyclic monophosphate (O‑Me‑cAMP) for 1 h using a pull‑down assay. Cell permeability was determined by the leakage rate of a fluorescein isothiocyanate fluorescent marker protein. AGE‑HSA treatment resulted in alterations in the structure and distribution of F‑actin and cortactin in a dose‑ and time‑dependent manner, while no effect was observed with HSA alone. The effect of AGE on the cytoskeleton was inhibited by the addition of O‑Me‑cAMP. AGE‑HSA significantly reduced the level of Rac1 activity (P<0.05); however, no effect was observed on total protein levels. Furthermore, AGE‑HSA treatment led to a significant increase in the permeability of endothelial cells (P<0.01), which was inhibited by O‑Me‑cAMP (P<0.01). The Rac1 signaling pathway is thus suggested to serve an important function in mediating AGE‑induced alterations in GEC morphology and function.

Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease.

PubMed

Hannemann, Anke; Cytlak, Urszula M; Rees, David C; Tewari, Sanjay; Gibson, John S

2014-09-15

The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with the abnormal form of haemoglobin (Hb), HbS, in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization and RBC sickling during hypoxia. We hypothesized that should 5HMF also inhibit the main cation pathways implicated in the dehydration of RBCs from SCD patients - the deoxygenation-induced cation pathway (Psickle), the Ca(2+)-activated K(+) channel (the Gardos channel) and the K(+)-Cl(-) cotransporter (KCC) - it would have a synergistic effect in protection against sickling, directly through interacting with HbS, and indirectly through maintaining hydration and reducing [HbS]. This study was therefore designed to investigate the effects of 5HMF on RBC volume and K(+) permeability in vitro. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation/re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca(2+) through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N-ethylmaleimide (NEM, 1 mm)-treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

10 CFR 60.122 - Siting criteria.

Code of Federal Regulations, 2010 CFR

2010-01-01

... with low horizontal and vertical permeability; (ii) Downward or dominantly horizontal hydraulic... permeability and low hydraulic gradient between the host rock and the surrounding hydrogeologic units. (3... REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES...

Cerebral peritumoral oedema study: does a single dynamic MR sequence assessing perfusion and permeability can help to differentiate glioblastoma from metastasis?

PubMed

Lehmann, Pierre; Saliou, Guillaume; de Marco, Giovanni; Monet, Pauline; Souraya, Stoquart-Elsankari; Bruniau, Alexis; Vallée, Jean Noel; Ducreux, Denis

2012-03-01

Our purpose was to differentiate glioblastoma from metastasis using a single dynamic MR sequence to assess perfusion and permeability parameters. 24 patients with glioblastoma or cerebral metastasis with peritumoral oedema were recruited and explored with a 3T MR unit. Post processing used DPTools software. Regions of interest were drawn around contrast enhancement to assess relative cerebral blood volume and permeability parameters. Around the contrast enhancement Glioblastoma present high rCBV with modification of the permeability, metastasis present slight modified rCBV without modification of permeability. In conclusion, peritumoral T2 hypersignal exploration associating morphological MR and functional MR parameters can help to differentiate cerebral metastasis from glioblastoma. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Continuous permeability measurements record healing inside the Wenchuan earthquake fault zone.

PubMed

Xue, Lian; Li, Hai-Bing; Brodsky, Emily E; Xu, Zhi-Qing; Kano, Yasuyuki; Wang, Huan; Mori, James J; Si, Jia-Liang; Pei, Jun-Ling; Zhang, Wei; Yang, Guang; Sun, Zhi-Ming; Huang, Yao

2013-06-28

Permeability controls fluid flow in fault zones and is a proxy for rock damage after an earthquake. We used the tidal response of water level in a deep borehole to track permeability for 18 months in the damage zone of the causative fault of the 2008 moment magnitude 7.9 Wenchuan earthquake. The unusually high measured hydraulic diffusivity of 2.4 × 10(-2) square meters per second implies a major role for water circulation in the fault zone. For most of the observation period, the permeability decreased rapidly as the fault healed. The trend was interrupted by abrupt permeability increases attributable to shaking from remote earthquakes. These direct measurements of the fault zone reveal a process of punctuated recovery as healing and damage interact in the aftermath of a major earthquake.

Benthic exchange and biogeochemical cycling in permeable sediments.

PubMed

Huettel, Markus; Berg, Peter; Kostka, Joel E

2014-01-01

The sandy sediments that blanket the inner shelf are situated in a zone where nutrient input from land and strong mixing produce maximum primary production and tight coupling between water column and sedimentary processes. The high permeability of the shelf sands renders them susceptible to pressure gradients generated by hydrodynamic and biological forces that modulate spatial and temporal patterns of water circulation through these sediments. The resulting dynamic three-dimensional patterns of particle and solute distribution generate a broad spectrum of biogeochemical reaction zones that facilitate effective decomposition of the pelagic and benthic primary production products. The intricate coupling between the water column and sediment makes it challenging to quantify the production and decomposition processes and the resultant fluxes in permeable shelf sands. Recent technical developments have led to insights into the high biogeochemical and biological activity of these permeable sediments and their role in the global cycles of matter.

Gas and Liquid Permeability Measurements in Wolfcamp Samples

NASA Astrophysics Data System (ADS)

Bhandari, A. R.; Flemings, P. B.; Ramiro-Ramirez, S.; Polito, P. J.

2017-12-01

Argon gas and liquid (dodecane) permeability measurements in three mixed quality Wolfcamp samples demonstrate it is possible to close multiple bedding parallel open artificial micro-fractures and obtain representative matrix permeability by applying two confining stress cycles at a constant pore pressure under effective stresses ranging from 6.9 MPa to 59.7 MPa. The fractured sample (with no bridging-cement in fractures) exhibited a three order decrease in permeability from 4.4×10-17 m2 to 2.1×10-20 m2. In contrast, the most intact sample exhibited initial liquid permeability of 1.61×10-19 m2 that declined gradually to 2.0×10-20 m2 over the same effective stress range. A third sample, that contained a bridging-cement (gypsum) fracture, exhibited much higher initial liquid permeability of 2.8×10-15 m2 and declined gradually to 1.3×10-17 m2 with stress; this suggested that it is difficult to close partially cemented fractures and that the permeability we measured was impacted by the presence of a propped-fracture and not the matrix. We developed a new permeability testing protocol and analytical approaches to interpret the evolution of fractures and resolve the matrix permeability using matrix permeability estimates based on initial pulse decay gas permeability measurements at effective stress of 6.9 MPa. The tested samples are an argillaceous siliceous siltstone facies within the Wolfcamp Formation. A better understanding of permeability will lead to new approaches to determine the best completion and production strategies and, more importantly, to reduce the high water cut problem in Wolfcamp reservoirs.

Investigation of the heat source(s) of the Surprise Valley Geothermal System, Northern California

NASA Astrophysics Data System (ADS)

Tanner, N.; Holt, C. D.; Hawkes, S.; McClain, J. S.; Safford, L.; Mink, L. L.; Rose, C.; Zierenberg, R. A.

2016-12-01

Concerns about environmental impacts and energy security have led to an increased interest in sustainable and renewable energy resources, including geothermal systems. It is essential to know the permeability structure and possible heat source(s) of a geothermal area in order to assess the capacity and extent of the potential resource. We have undertaken geophysical surveys at the Surprise Valley Hot Springs in Cedarville, California to characterize essential parameters related to a fault-controlled geothermal system. At present, the heat source(s) for the system are unknown. Igneous bodies in the area are likely too old to have retained enough heat to supply the system, so it is probable that fracture networks provide heat from some deeper or more distributed heat sources. However, the fracture system and permeability structure remain enigmatic. The goal of our research is to identify the pathways for fluid transport within the Surprise Valley geothermal system using a combination of geophysical methods including active seismic surveys and short- and long-period magnetotelluric (MT) surveys. We have collected 14 spreads, consisting of 24 geophones each, of active-source seismic data. We used a "Betsy Gun" source at 8 to 12 locations along each spread and have collected and analyzed about 2800 shot-receiver pairs. Seismic velocities reveal shallow lake sediments, as well as velocities consistent with porous basalts. The latter, with velocities of greater than 3.0 km/s, lie along strike with known hot springs and faulted and tilted basalt outcrops outside our field area. This suggests that basalts may provide a permeable pathway through impermeable lake deposits. We conducted short-period (10Hz-60kHz) MT measurements at 33 stations. Our short-period MT models indicate shallow resistive blocks (>100Ωm) with a thin cover of more conductive sediments ( 10Ωm) at the surface. Hot springs are located in gaps between resistive blocks and are connected to deeper low resistivity zones ( 1Ωm), suggestive of a fluid pathway. In order to refine these models and extend them to greater depths, we have deployed long-period (0.002Hz-10Hz) MT instruments in three locations. The data were collected over several weeks and are currently being processed and analyzed.

Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

PubMed Central

Selby, P. J.; Lopes, N.; Mundy, J.; Crofts, M.; Millar, J. L.; McElwain, T. J.

1987-01-01

A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID:3111515

Compiling and Mapping Global Permeability of the Unconsolidated and Consolidated Earth: GLobal HYdrogeology MaPS 2.0 (GLHYMPS 2.0)

NASA Astrophysics Data System (ADS)

Huscroft, Jordan; Gleeson, Tom; Hartmann, Jens; Börker, Janine

2018-02-01

The spatial distribution of subsurface parameters such as permeability are increasingly relevant for regional to global climate, land surface, and hydrologic models that are integrating groundwater dynamics and interactions. Despite the large fraction of unconsolidated sediments on Earth's surface with a wide range of permeability values, current global, high-resolution permeability maps distinguish solely fine-grained and coarse-grained unconsolidated sediments. Representative permeability values are derived for a wide variety of unconsolidated sediments and applied to a new global map of unconsolidated sediments to produce the first geologically constrained, two-layer global map of shallower and deeper permeability. The new mean logarithmic permeability of the Earth's surface is -12.7 ± 1.7 m2 being 1 order of magnitude higher than that derived from previous maps, which is consistent with the dominance of the coarser sediments. The new data set will benefit a variety of scientific applications including the next generation of climate, land surface, and hydrology models at regional to global scales.

Permeability Estimation Directly From Logging-While-Drilling Induced Polarization Data

NASA Astrophysics Data System (ADS)

Fiandaca, G.; Maurya, P. K.; Balbarini, N.; Hördt, A.; Christiansen, A. V.; Foged, N.; Bjerg, P. L.; Auken, E.

2018-04-01

In this study, we present the prediction of permeability from time domain spectral induced polarization (IP) data, measured in boreholes on undisturbed formations using the El-log logging-while-drilling technique. We collected El-log data and hydraulic properties on unconsolidated Quaternary and Miocene deposits in boreholes at three locations at a field site in Denmark, characterized by different electrical water conductivity and chemistry. The high vertical resolution of the El-log technique matches the lithological variability at the site, minimizing ambiguity in the interpretation originating from resolution issues. The permeability values were computed from IP data using a laboratory-derived empirical relationship presented in a recent study for saturated unconsolidated sediments, without any further calibration. A very good correlation, within 1 order of magnitude, was found between the IP-derived permeability estimates and those derived using grain size analyses and slug tests, with similar depth trends and permeability contrasts. Furthermore, the effect of water conductivity on the IP-derived permeability estimations was found negligible in comparison to the permeability uncertainties estimated from the inversion and the laboratory-derived empirical relationship.

The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

PubMed Central

Liu, Jiahui; Liu, Libo; Chao, Shuo; Liu, Yunhui; Liu, Xiaobai; Zheng, Jian; Chen, Jiajia; Gong, Wei; Teng, Hao; Li, Zhen; Wang, Ping; Xue, Yixue

2017-01-01

This study was performed to determine whether EMAP II increases the permeability of the blood-tumor barrier (BTB) by affecting the expression of miR-330-3p as well as its possible mechanisms. We determined the over-expression of miR-330-3p in glioma microvascular endothelial cells (GECs) by Real-time PCR. Endothelial monocyte-activating polypeptide-II (EMAP-II) significantly decreased the expression of miR-330-3p in GECs. Pre-miR-330-3p markedly decreased the permeability of BTB and increased the expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5, however, anti-miR-330-3p had the opposite effects. Anti-miR-330-3p could enhance the effect of EMAP-II on increasing the permeability of BTB, however, pre-miR-330-3p partly reversed the effect of EMAP-II on that. Similarly, anti-miR-330-3p improved the effects of EMAP-II on increasing the expression levels of PKC-α and p-PKC-α in GECs and pre-miR-330-3p partly reversed the effects. MiR-330-3p could target bind to the 3′UTR of PKC-α. The results of in vivo experiments were similar to those of in vitro experiments. These suggested that EMAP-II could increase the permeability of BTB through inhibiting miR-330-3p which target negative regulation of PKC-α. Pre-miR-330-3p and PKC-α inhibitor decreased the BTB permeability and up-regulated the expression levels of ZO-1, occludin and claudin-5 while anti-miR-330-3p and PKC-α activator brought the reverse effects. Compared with EMAP-II, anti-miR-330-3p and PKC-α activator alone, the combination of the three combinations significantly increased the BTB permeability. EMAP-II combined with anti-miR-330-3p and PKCα activator could enhance the DOX’s effects on inhibiting the cell viabilities and increasing the apoptosis of U87 glioma cells. Our studies suggest that low-dose EMAP-II up-regulates the expression of PKC-α and increases the activity of PKC-α by inhibiting the expression of miR-330-3p, reduces the expression of ZO-1, occludin and claudin-5, and thereby increasing the permeability of BTB. The results can provide a new strategy for the comprehensive treatment of glioma. PMID:29311822

Fracture network topology and characterization of structural permeability

NASA Astrophysics Data System (ADS)

Hansberry, Rowan; King, Rosalind; Holford, Simon

2017-04-01

There are two fundamental requirements for successful geothermal development: elevated temperatures at accessible depths, and a reservoir from which fluids can be extracted. The Australian geothermal sector has successfully targeted shallow heat, however, due in part to the inherent complexity of targeting permeability, obtaining adequate flow rates for commercial production has been problematic. Deep sedimentary aquifers are unlikely to be viable geothermal resources due to the effects of diagenetic mineral growth on rock permeability. Therefore, it is likely structural permeability targets, exploiting natural or induced fracture networks will provide the primary means for fluid flow in geothermal, as well as unconventional gas, reservoirs. Recent research has focused on the pattern and generation of crustal stresses across Australia, while less is known about the resultant networks of faults, joints, and veins that can constitute interconnected sub-surface permeability pathways. The ability of a fracture to transmit fluid is controlled by the orientation and magnitude of the in-situ stress field that acts on the fracture walls, rock strength, and pore pressure, as well as fracture properties such as aperture, orientation, and roughness. Understanding the distribution, orientation and character of fractures is key to predicting structural permeability. This project focuses on extensive mapping of fractures over various scales in four key Australian basins (Cooper, Otway, Surat and Perth) with the potential to host geothermal resources. Seismic attribute analysis is used in concert with image logs from petroleum wells, and field mapping to identify fracture networks that are usually not resolved in traditional seismic interpretation. We use fracture network topology to provide scale-invariant characterisation of fracture networks from multiple data sources to assess similarity between data sources, and fracture network connectivity. These results are compared with other permeability indicators such as drilling fluid losses, and pore pressure measurements. Initial work with these techniques has led to new developments in our ability to image subsurface faults and fractures at a variety of scales from independent datasets. We establish a strong relationship between features identified using seismic attribute analysis and interpreted natural fractures. However, care must be taken to use these methods in a case-by-case basis, as controls on fracture distribution and orientation can vary significantly with both regional and local influences. These results outline and effective method by which structural permeability can be assessed with existing petroleum datasets. However, unlike the broad stress field, mapping fracture orientation and characteristics within the Australian Continent is complicated as the distribution, geometry, areal extent and connectivity of fracture networks can vary significantly.

In situ coagulation versus pre-coagulation for gravity-driven membrane bioreactor during decentralized sewage treatment: Permeability stabilization, fouling layer formation and biological activity.

PubMed

Ding, An; Wang, Jinlong; Lin, Dachao; Tang, Xiaobin; Cheng, Xiaoxiang; Li, Guibai; Ren, Nanqi; Liang, Heng

2017-12-01

Gravity-driven membrane filtration systems are promising for decentralized sewage treatment due to their low energy consumption and low maintenance. However, the low stable permeability/flux is currently limiting their wider application. With the ultimate goal of increasing permeability, the aim of this study was to evaluate the effect of coagulation (in situ coagulation and pre-coagulation) on the performance of a gravity-driven membrane bioreactor (GDMBR) during treatment of synthetic sewage. Results show that in situ coagulation significantly increased permeability (more than two-fold); however, no stabilization of permeability occurred over the whole operation, when non-coagulated and pre-coagulated reactors were compared. The high permeability observed was attributed to the accumulated aluminium floc in the reactor, which prevented formation of fluorescent microbial metabolites (aromatic and tryptophan proteins, as well as fulvic acids), and further avoided membrane pore blocking. In addition, the surface porosity of the fouling layer was improved (from 11.2% to 32.4% for non-coagulated and in situ coagulated reactors). The unstable permeability was possibly associated with lower biological processes within the fouling layer. These might include lower adenosine triphosphate (ATP) content and lower fluorescent metabolites from the extracellular polymeric substances (EPS) caused by the accumulated Al (compared with the control). On the other hand, pre-coagulation improved the level of stable permeability compared with the control (80 versus 40 L/m 2 h bar), mainly because pre-coagulation decreased the EPS content and also maintained high ATP content of the fouling layer. In addition, both coagulation processes reduced the total filtration resistance, mainly the hydraulically reversible resistance and cake layer resistance, which could lower the cleaning frequency. Overall, coagulation could greatly increase the removal efficiency and improve the GDMBR permeability, which would make the process suitable for decentralized wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyethylene glycol versus dual sugar assay for gastrointestinal permeability analysis: is it time to choose?

PubMed Central

van Wijck, Kim; Bessems, Babs AFM; van Eijk, Hans MH; Buurman, Wim A; Dejong, Cornelis HC; Lenaerts, Kaatje

2012-01-01

Background Increased intestinal permeability is an important measure of disease activity and prognosis. Currently, many permeability tests are available and no consensus has been reached as to which test is most suitable. The aim of this study was to compare urinary probe excretion and accuracy of a polyethylene glycol (PEG) assay and dual sugar assay in a double-blinded crossover study to evaluate probe excretion and the accuracy of both tests. Methods Gastrointestinal permeability was measured in nine volunteers using PEG 400, PEG 1500, and PEG 3350 or lactulose-rhamnose. On 4 separate days, permeability was analyzed after oral intake of placebo or indomethacin, a drug known to increase intestinal permeability. Plasma intestinal fatty acid binding protein and calprotectin levels were determined to verify compromised intestinal integrity after indomethacin consumption. Urinary samples were collected at baseline, hourly up to 5 hours after probe intake, and between 5 and 24 hours. Urinary excretion of PEG and sugars was determined using high-pressure liquid chromatography-evaporative light scattering detection and liquid chromatography-mass spectrometry, respectively. Results Intake of indomethacin increased plasma intestinal fatty acid-binding protein and calprotectin levels, reflecting loss of intestinal integrity and inflammation. In this state of indomethacin-induced gastrointestinal compromise, urinary excretion of the three PEG probes and lactulose increased compared with placebo. Urinary PEG 400 excretion, the PEG 3350/PEG 400 ratio, and the lactulose/rhamnose ratio could accurately detect indomethacin-induced increases in gastrointestinal permeability, especially within 2 hours of probe intake. Conclusion Hourly urinary excretion and diagnostic accuracy of PEG and sugar probes show high concordance for detection of indomethacin-induced increases in gastrointestinal permeability. This comparative study improves our knowledge of permeability analysis in man by providing a clear overview of both tests and demonstrates equivalent performance in the current setting. PMID:22888267

Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

NASA Astrophysics Data System (ADS)

Roy Chaudhuri, Tista

An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre-treated with sHH-inhibitor led to a 90% lifespan extension in animals that received a single cycle of the combined regimen, and a 200% extension in animals receiving 3-cycles of treatment, compared to control animals or those receiving either of the agents alone. We surmise that direct or indirect modulation of tumor vasculature can provide new opportunities for combination therapies that could improve delivery and efficacy of both small- and large- molecular weight agents in treatment-resistant solid tumors.

Integrated petrophysical and reservoir characterization workflow to enhance permeability and water saturation prediction

NASA Astrophysics Data System (ADS)

Al-Amri, Meshal; Mahmoud, Mohamed; Elkatatny, Salaheldin; Al-Yousef, Hasan; Al-Ghamdi, Tariq

2017-07-01

Accurate estimation of permeability is essential in reservoir characterization and in determining fluid flow in porous media which greatly assists optimize the production of a field. Some of the permeability prediction techniques such as Porosity-Permeability transforms and recently artificial intelligence and neural networks are encouraging but still show moderate to good match to core data. This could be due to limitation to homogenous media while the knowledge about geology and heterogeneity is indirectly related or absent. The use of geological information from core description as in Lithofacies which includes digenetic information show a link to permeability when categorized into rock types exposed to similar depositional environment. The objective of this paper is to develop a robust combined workflow integrating geology and petrophysics and wireline logs in an extremely heterogeneous carbonate reservoir to accurately predict permeability. Permeability prediction is carried out using pattern recognition algorithm called multi-resolution graph-based clustering (MRGC). We will bench mark the prediction results with hard data from core and well test analysis. As a result, we showed how much better improvements are achieved in the permeability prediction when geology is integrated within the analysis. Finally, we use the predicted permeability as an input parameter in J-function and correct for uncertainties in saturation calculation produced by wireline logs using the classical Archie equation. Eventually, high level of confidence in hydrocarbon volumes estimation is reached when robust permeability and saturation height functions are estimated in presence of important geological details that are petrophysically meaningful.