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.
Rodríguez, Isabel; Vázquez, José Antonio; Pastrana, Lorenzo; Khutoryanskiy, Vitaliy V
2017-08-30
This study investigates how both bioadhesive polymers (chitosan, hyaluronic acid and alginate) and permeability enhancers (ethylene glycol- bis(2-aminoethylether)- N, N, N', N'- tetraacetic acid (EGTA) and hydroxypropyl-ß-cyclodextrin) influence the permeability of the anti-glaucoma drug timolol maleate through ex vivo bovine corneas. Our results showed that only the permeability enhancers alone were able to increase drug permeability, whereas the polymers significantly reduced drug permeation, and however, they increased the pre-corneal residence of timolol. Ternary systems (polymer-enhancer-drug) showed a reduced drug permeability compared to the polymers alone. Fluorescence microscopy analysis of the epithelium surface confirmed there was no evidence of epithelial disruption caused by these formulations, suggesting that polymer-enhancer interactions reduce drug solubilization and counteract the disruptive effect of the permeability enhancers on the surface of the cornea. Further mucoadhesive tests, revealed a stable interaction of chitosan and hyaluronic acid with the epithelium, while alginate showed poor mucoadhesive properties. The differences in mucoadhesion correlated with the permeability of timolol maleate observed, i.e. formulations containing mucoadhesive polymers showed lower drug permeabilities. The results of the present study indicate polymers acting as an additional barrier towards drug permeability which is even more evident in the presence of permeability enhancers like EGTA and hydroxypropyl-ß-cyclodextrin. Then, this study highlights the need to adequately select additives intended for ocular applications since interactions between them can have opposite results to what expected in terms of drug permeability. Copyright © 2017 Elsevier B.V. All rights reserved.
Effect of permeability enhancers on paracellular permeability of acyclovir.
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.
Analysis of the Thermal and Hydraulic Stimulation Program at Raft River, Idaho
NASA Astrophysics Data System (ADS)
Bradford, Jacob; McLennan, John; Moore, Joseph; Podgorney, Robert; Plummer, Mitchell; Nash, Greg
2017-05-01
The Raft River geothermal field, located in southern Idaho, roughly 100 miles northwest of Salt Lake City, is the site of a Department of Energy Enhanced Geothermal System project designed to develop new techniques for enhancing the permeability of geothermal wells. RRG-9 ST1, the target stimulation well, was drilled to a measured depth of 5962 ft. and cased to 5551 ft. The open-hole section of the well penetrates Precambrian quartzite and quartz monzonite. The well encountered a temperature of 282 °F at its base. Thermal and hydraulic stimulation was initiated in June 2013. Several injection strategies have been employed. These strategies have included the continuous injection of water at temperatures ranging from 53 to 115 °F at wellhead pressures of approximately 275 psi and three short-term hydraulic stimulations at pressures up to approximately 1150 psi. Flow rates, wellhead and line pressures and fluid temperatures are measured continuously. These data are being utilized to assess the effectiveness of the stimulation program. As of August 2014, nearly 90 million gallons have been injected. A modified Hall plot has been used to characterize the relationships between the bottom-hole flowing pressure and the cumulative injection fluid volume. The data indicate that the skin factor is decreased, and/or the permeability around the wellbore has increased since the stimulation program was initiated. The injectivity index also indicates a positive improvement with values ranging from 0.15 gal/min psi in July 2013 to 1.73 gal/min psi in February 2015. Absolute flow rates have increased from approximately 20 to 475 gpm by February 2 2015. Geologic, downhole temperature and seismic data suggest the injected fluid enters a fracture zone at 5650 ft and then travels upward to a permeable horizon at the contact between the Precambrian rocks and the overlying Tertiary sedimentary and volcanic deposits. The reservoir simulation program FALCON developed at the Idaho National Laboratory is being used to simulate and visualize the effects of the injection. The simulation model uses a discrete fracture network generated for RRG-9 using acoustic borehole imaging and analysis of microseismic activity. By adjusting the permeability of the fractures, a pressure history match for the first part of the stimulation program was obtained. The results of this model indicate that hydraulic fracturing is the dominant mechanism for permeability improvement for this part of the stimulation program.
Permeability of stylolite-bearing chalk
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lind, I.; Nykjaer, O.; Priisholm, S.
1994-11-01
Permeabilities were measured on core plugs from stylolite-bearing chalk of the Gorm field in the Danish North Sea. Air and liquid permeabilities were measured in directions parallel to and perpendicular to the stylolite surface. Permeability was measured with sleeve pressure equal to in-situ reservoir stress. Permeabilities of plugs with stylolites but without stylolite-associated fractures were equal in the two directions. The permeability is equal to the matrix permeability of non-stylolite-bearing chalk. In contrast, when fractures were associated with the stylolites, permeability was enhanced. The enhancement was most significant in the horizontal direction parallel to the stylolites.
Cancel, Limary M; Tarbell, John M; Ben-Jebria, Abdellaziz
2004-09-01
Transdermal drug delivery offers an alternative to injections and oral medication but is limited by the low skin permeability of most drugs. The use of low-frequency ultrasound over long periods of time, typically over an hour, has been shown to enhance skin permeability, a phenomenon referred to as sonophoresis. In this study, we investigated the effects of short time sonication of human skin at 20 kHz and at variable intensities and duty cycles on the dynamics of fluorescein transport across the skin (permeability) as well as the changes in the skin's structural integrity (electrical resistance). We found that a short application of ultrasound enhanced the transport of fluorescein across human skin by a factor in the range of 2-9 for full thickness skin samples and by a factor in the range of 2-28 000 for heat-stripped stratum corneum samples (however, samples with very high (10(3)) enhancement were likely to have been damaged by ultrasound). The electrical resistance of the skin decreased by an average of 20% for full thickness samples and 58% for stratum corneum samples. Increasing the duty cycle from 10 to 60% caused a significant increase in permeability enhancement from 2.3 to 9.1, and an increase in intensity from 8 to 23 mW cm(-2) induced a significant increase in permeability enhancement from 2 to 7.4, indicating a clear dependence of the permeability on both duty cycle and intensity. The increase in solute flux upon ultrasound exposure was immediate, demonstrating for the first time the fast response dynamics of sonophoretic enhancement. In addition, a quantitative analysis of the thermal and convective dispersion effects associated with ultrasound application showed that each contributes significantly to the overall permeability enhancement observed.
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.
Rapid and reversible enhancement of blood–brain barrier permeability using lysophosphatidic acid
On, Ngoc H; Savant, Sanjot; Toews, Myron; Miller, Donald W
2013-01-01
The present study characterizes the effects of lysophosphatidic acid (LPA) on blood–brain barrier (BBB) permeability focusing specifically on the time of onset, duration, and magnitude of LPA-induced changes in cerebrovascular permeability in the mouse using both magnetic resonance imaging (MRI) and near infrared fluorescence imaging (NIFR). Furthermore, potential application of LPA for enhanced drug delivery to the brain was also examined by measuring the brain accumulation of radiolabeled methotrexate. Exposure of primary cultured brain microvessel endothelial cells (BMECs) to LPA produced concentration-dependent increases in permeability that were completely abolished by clostridium toxin B. Administration of LPA disrupted BBB integrity and enhanced the permeability of small molecular weight marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRdye800cwPEG, and the P-glycoprotein efflux transporter probe, Rhodamine 800 (R800). The increase in BBB permeability occurred within 3 minutes after LPA injection and barrier integrity was restored within 20 minutes. A decreased response to LPA on large macromolecule BBB permeability was observed after repeated administration. The administration of LPA also resulted in 20-fold enhancement of radiolabeled methotrexate in the brain. These studies indicate that administration of LPA in combination with therapeutic agents may increase drug delivery to the brain. PMID:24045401
A relationship between porosity and permeability of carbonate rock reservoirs
NASA Astrophysics Data System (ADS)
Lee, J.; Park, Y.; Jo, Y.; Jeong, J.; Eom, S.
2009-12-01
Most of oil reservoirs in the world occur in carbonate rocks. Thus, characterization of the carbonate reservoirs, including understanding the correlation between porosity and permeability is essentially required to enhance oil recovery. Compared with the other sedimentary rocks such as sandstone and shale, the carbonate rocks would exhibit a wide variety of vertical and horizontal heterogeneities. In general, pores of the carbonate rocks can be affected by mineral dissolution, replacement by other minerals and re-crystallization, which are the post-depositional processes. Permeability has been estimated at a wide scale by thin section image analysis, rock core experiments, geophysical well logging data and large scale aquifer tests. For the same porosity, the permeability might show a wide variation. In this study, a large number of the porosity and the permeability data pairs for world wide carbonate rocks (reservoirs) were collected from many literatures. The porosity and permeability data were grouped according to test scale, the reservoir location and the rock types. As is already known, the relation showed a rather scattered distribution also in this study, not monotonous, which indicates that higher porosity does not mean higher permeability of the rock formation. This study provides the analysis results and implications for oil production of the carbonate reservoirs. This research was funded by Energy Efficiency and Resources Program of KETEP (Korea Institute of Energy Technology Evaluation and Planning), Grant No. 2009T100200058.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chace, D.A.; Roberts, R.M.; Palmer, J.B.
WIPP Salado Hydrology Program Data Report {number_sign}3 presents hydrologic data collected during permeability testing, coupled permeability and hydrofracture testing, and gas-threshold-pressure testing of the Salado Formation performed from November 1991 through October 1995. Fluid-pressure monitoring data representing August 1989 through May 1995 are also included. The report presents data from the drilling and testing of three boreholes associated with the permeability testing program, nine boreholes associated with the coupled permeability and hydrofracture testing program, and three boreholes associated with the gas-threshold-pressure testing program. The purpose of the permeability testing program was to provide data with which to interpret the disturbedmore » and undisturbed permeability and pore pressure characteristics of the different Salado Formation lithologies. The purpose of the coupled permeability and hydrofracture testing program was to provide data with which to characterize the occurrence, propagation, and direction of pressure induced fractures in the Salado Formation lithologies, especially MB139. The purpose of the gas-threshold-pressure testing program was to provide data with which to characterize the conditions under which pressurized gas displaces fluid in the brine-saturated Salado Formation lithologies. All of the holes were drilled from the WIPP underground facility 655 m below ground surface in the Salado Formation.« less
Enhanced CAH dechlorination in a low permeability, variably-saturated medium
Martin, J.P.; Sorenson, K.S.; Peterson, L.N.; Brennan, R.A.; Werth, C.J.; Sanford, R.A.; Bures, G.H.; Taylor, C.J.; ,
2002-01-01
An innovative pilot-scale field test was performed to enhance the anaerobic reductive dechlorination (ARD) of chlorinated aliphatic hydrocarbons (CAHs) in a low permeability, variably-saturated formation. The selected technology combines the use of a hydraulic fracturing (fracking) technique with enhanced bioremediation through the creation of highly-permeable sand- and electron donor-filled fractures in the low permeability matrix. Chitin was selected as the electron donor because of its unique properties as a polymeric organic material and based on the results of lab studies that indicated its ability to support ARD. The distribution and impact of chitin- and sand-filled fractures to the system was evaluated using hydrologic, geophysical, and geochemical parameters. The results indicate that, where distributed, chitin favorably impacted redox conditions and supported enhanced ARD of CAHs. These results indicate that this technology may be a viable and cost-effective approach for remediation of low-permeability, variably saturated systems.
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
A new structure of permeable pavement for mitigating urban heat island.
Liu, Yong; Li, Tian; Peng, Hangyu
2018-09-01
The urban heat island (UHI) effect has been a great threat to human habitation, and how to mitigate this problem has been a global concern over decades. This paper addresses the cooling effect of a novel permeable pavement called evaporation-enhancing permeable pavement, which has capillary columns in aggregate and a liner at the bottom. To explore the efficiency of mitigating the UHI, bench-scale permeable pavement units with capillary columns were developed and compared with conventional permeable pavement. Criteria of capillary capacities of the column, evaporation rates, and surface temperature of the pavements were monitored under simulated rainfall and Shanghai local weather conditions. Results show the capillary column was important in increasing evaporation by lifting water from the bottom to the surface, and the evaporation-enhancing permeable pavement was cooler than a conventional permeable pavement by as much as 9.4°C during the experimental period. Moreover, the cooling effect of the former pavement could persist more than seven days under the condition of no further rainfall. Statistical analysis result reveals that evaporation-enhancing permeable pavement can mitigate the UHI effect significantly more than a conventional permeable pavement. Copyright © 2018 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Riffault, J.; Dempsey, D. E.; Karra, S.; Archer, R.
2016-12-01
To create an Enhanced Geothermal System (EGS), high pressure injection is undertaken to reactivate pre-existing fractures and enhance their permeability. During the 2011 Paralana-2 EGS stimulation in South Australia, both injectivity, the ratio of the injection rate to wellhead pressure, and seismicity were recorded. An increase in injectivity indicates that permeability has been enhanced, although it does not constrain the location or magnitude of the change. Induced earthquakes, a spatiotemporal dataset, can confine the range of possible scenarios for permeability evolution. We consider a model in which the number of hypocenters recorded per unit of area of the injection plane (the hypocenter density) is proportional to fluid pressure increase. Then an inverse modelling approach is employed to recover the permeability enhancement distribution that is consistent with both the recorded changes in injectivity and seismicity. Our forward model is radial Darcy-flow with permeability a prescribed function of time and distance, i.e., k(r,t). Initially, we identify a range of permeability evolution scenarios that reproduce the observed injectivity increase with time. Thus, injectivity observations on their own are insufficient to constrain k(r,t). Then, we calibrate k(r,t) for a close match between the modelled pressure distribution and that inferred from the hypocenter density observations using a simple proportionality constant. The resulting permeability model is the one most likely to approximate permeability evolution during the Paralana stimulation.
Manga, Michael; Beresnev, Igor; Brodsky, Emily E.; Elkhoury, Jean E.; Elsworth, Derek; Ingebritsen, Steve E.; Mays, David C.; Wang, Chi-Yuen
2012-01-01
Oscillations in stress, such as those created by earthquakes, can increase permeability and fluid mobility in geologic media. In natural systems, strain amplitudes as small as 10–6 can increase discharge in streams and springs, change the water level in wells, and enhance production from petroleum reservoirs. Enhanced permeability typically recovers to prestimulated values over a period of months to years. Mechanisms that can change permeability at such small stresses include unblocking pores, either by breaking up permeability-limiting colloidal deposits or by mobilizing droplets and bubbles trapped in pores by capillary forces. The recovery time over which permeability returns to the prestimulated value is governed by the time to reblock pores, or for geochemical processes to seal pores. Monitoring permeability in geothermal systems where there is abundant seismicity, and the response of flow to local and regional earthquakes, would help test some of the proposed mechanisms and identify controls on permeability and its evolution.
Fracturing Behavior of Methane-Hydrate-Bearing Sediment
NASA Astrophysics Data System (ADS)
Konno, Y.; Jin, Y.; Yoneda, J.; Uchiumi, T.; Shinjou, K.; Nagao, J.
2016-12-01
As a part of a Japanese national hydrate research program (MH21, funded by the Ministry of Economy, Trade, and Industry), we performed laboratory experiments of hydraulic fracturing in methane-hydrate-bearing sediment. Distilled water was injected into methane-hydrate-bearing sand which was artificially made in a tri-axial pressure cell. X-ray computed tomography revealed that tensile failure was occurred after a rapid drop in the injection pressure. It was found that generated fractures cause a significant increase in the effective water permeability of hydrate-bearing sand. The result contributes fundamental understanding of the accumulation mechanism of gas hydrates in sediments and shows that hydraulic fracturing is one of promising enhanced recovery methods for low-permeable gas hydrate reservoirs.
Investigation of the Profile Control Mechanisms of Dispersed Particle Gel
Zhao, Guang; Dai, Caili; Zhao, Mingwei
2014-01-01
Dispersed particle gel (DPG) particles of nano- to micron- to mm-size have been prepared successfully and will be used for profile control treatment in mature oilfields. The profile control and enhanced oil recovery mechanisms of DPG particles have been investigated using core flow tests and visual simulation experiments. Core flow test results show that DPG particles can easily be injected into deep formations and can effectively plug the high permeability zones. The high profile improvement rate improves reservoir heterogeneity and diverts fluid into the low permeability zone. Both water and oil permeability were reduced when DPG particles were injected, but the disproportionate permeability reduction effect was significant. Water permeability decreases more than the oil permeability to ensure that oil flows in its own pathways and can easily be driven out. Visual simulation experiments demonstrate that DPG particles can pass directly or by deformation through porous media and enter deep formations. By retention, adsorption, trapping and bridging, DPG particles can effectively reduce the permeability of porous media in high permeability zones and divert fluid into a low permeability zone, thus improving formation profiles and enhancing oil recovery. PMID:24950174
Crustal permeability: Introduction to the special issue
Ingebritsen, Steven E.; Gleeson, Tom
2015-01-01
The topic of crustal permeability is of broad interest in light of the controlling effect of permeability on diverse geologic processes and also timely in light of the practical challenges associated with emerging technologies such as hydraulic fracturing for oil and gas production (‘fracking’), enhanced geothermal systems, and geologic carbon sequestration. This special issue of Geofluids is also motivated by the historical dichotomy between the hydrogeologic concept of permeability as a static material property that exerts control on fluid flow and the perspective of economic geologists, geophysicists, and crustal petrologists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. Issues associated with fracking, enhanced geothermal systems, and geologic carbon sequestration have already begun to promote a constructive dialog between the static and dynamic views of permeability, and here we have made a conscious effort to include both viewpoints. This special issue also focuses on the quantification of permeability, encompassing both direct measurement of permeability in the uppermost crust and inferential permeability estimates, mainly for the deeper crust.
Enhancement of hydrogen gas permeability in electrically aligned MWCNT-PMMA composite membranes.
Kumar, Sumit; Sharma, Anshu; Tripathi, Balram; Srivastava, Subodh; Agrawal, Shweta; Singh, M; Awasthi, Kamlendra; Vijay, Y K
2010-10-01
The multi-walled carbon nanotube (MWCNT) dispersed polymethylmethacrylate (PMMA) composite membranes have been prepared for hydrogen gas permeation application. Composite membranes are characterized by Raman spectroscopy, optical microscopy, X-ray diffraction, electrical measurements and gas permeability measurements. The effect of electric field alignment of MWCNT in PMMA matrix on gas permeation has been studied for hydrogen gas. The permeability measurements indicated that the electrically aligned MWCNT in PMMA has shown almost 2 times higher permeability for hydrogen gas as compare to randomly dispersed MWCNT in PMMA. The enhancement in permeability is explained on the basis of well aligned easy channel provided by MWCNT in electrically aligned sample. The effect of thickness of membrane on the gas permeability also studied and thickness of about 30microm found to be optimum thickness for fast hydrogen gas permeates.
A Systematic Procedure to Describe Shale Gas Permeability Evolution during the Production Process
NASA Astrophysics Data System (ADS)
Jia, B.; Tsau, J. S.; Barati, R.
2017-12-01
Gas flow behavior in shales is complex due to the multi-physics nature of the process. Pore size reduces as the in-situ stress increases during the production process, which will reduce intrinsic permeability of the porous media. Slip flow/pore diffusion enhances gas apparent permeability, especially under low reservoir pressures. Adsorption not only increases original gas in place but also influences gas flow behavior because of the adsorption layer. Surface diffusion between free gas and adsorption phase enhances gas permeability. Pore size reduction and the adsorption layer both have complex impacts on gas apparent permeability and non-Darcy flow might be a major component in nanopores. Previously published literature is generally incomplete in terms of coupling of all these four physics with fluid flow during gas production. This work proposes a methodology to simultaneously take them into account to describe a permeability evolution process. Our results show that to fully describe shale gas permeability evolution during gas production, three sets of experimental data are needed initially: 1) intrinsic permeability under different in-situ stress, 2) adsorption isotherm under reservoir conditions and 3) surface diffusivity measurement by the pulse-decay method. Geomechanical effects, slip flow/pore diffusion, adsorption layer and surface diffusion all play roles affecting gas permeability. Neglecting any of them might lead to misleading results. The increasing in-situ stress during shale gas production is unfavorable to shale gas flow process. Slip flow/pore diffusion is important for gas permeability under low pressures in the tight porous media. They might overwhelm the geomechanical effect and enhance gas permeability at low pressures. Adsorption layer reduces the gas permeability by reducing the effective pore size, but the effect is limited. Surface diffusion increases gas permeability more under lower pressures. The total gas apparent permeability might keep increasing during the gas production process when the surface diffusivity is larger than a critical value. We believe that our workflow proposed in this study will help describe shale gas permeability evolution considering all the underlying physics altogether.
Ghai, Damanjeet; Sinha, Vivek Ranjan
2012-07-01
To enhance the bioavailability of the poorly water-soluble drug talinolol, a self-nanoemulsifying drug delivery system (SNEDDS) comprising 5% (w/v) Brij-721 ethanolic solution (Smix), triacetin, and water, in the ratio of 40:20:40 (% w/w) was developed by constructing pseudo-ternary phase diagrams and evaluated for droplet size, polydispersity index, and surface morphology of nanoemulsions. The effect of nanodrug carriers on drug release and permeability was assessed using stripped porcine jejunum and everted rat gut sac method and compared with hydroalcoholic drug solution, oily solution, and conventional emulsion and suspension. The SNEDDS showed a significant (P < 0.001) increase in drug release, permeability, and in vivo bioavailability as compared to drug suspension. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. In this study, a self-nanoemulsifying drug delivery system was utilized to enhance the bioavailability of the poorly water-soluble beta-blocker talinolol. Significant increase in drug release, permeability, and in vivo bioavailability were demonstrated as compared to standard drug suspension. Copyright © 2012 Elsevier Inc. All rights reserved.
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.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Riffault, Jeremy; Dempsey, David; Karra, Satish
The goal of hydraulic stimulation is to increase formation permeability in the near vicinity of a well. However, there remain technical challenges around measuring the outcome of this operation. During two Enhanced Geothermal System (EGS) stimulations in South Australia, Paralana in 2011 and Habanero in 2003, extensive catalogs of microseismicity were recovered. It is often assumed that shear failure of existing fractures is the main mechanism behind both the induced earthquakes and any permeability enhancement. This underpins a common notion, that the seismically active volume is also the stimulated reservoir. In this paper, we compute the density of earthquake hypocentersmore » and provide evidence that, under certain conditions, this spatiotemporal quantity is a reasonable proxy for pore pressure increase. We then apply an inverse modeling approach that uses the earthquake observations and a modified reservoir simulator to estimate the parameters of a permeability evolution relation. The regime implied by the data indicates that most permeability enhancement occurred very near to the wellbore and was not coincident with the bulk of the seismicity, whose volume was about two orders of magnitude larger. Thus, we conclude that, in some cases, it is possible for permeability enhancement and induced seismicity to be decoupled, in which case the seismically active volume is a poor indicator of the stimulated reservoir. Our results raise serious questions about the effectiveness of hydroshearing as a stimulation mechanism in EGS. Finally, this study extends our understanding of the complex processes linking earthquakes, fluid pressure, and permeability in both natural and engineered settings.« less
Riffault, Jeremy; Dempsey, David; Karra, Satish; ...
2018-06-21
The goal of hydraulic stimulation is to increase formation permeability in the near vicinity of a well. However, there remain technical challenges around measuring the outcome of this operation. During two Enhanced Geothermal System (EGS) stimulations in South Australia, Paralana in 2011 and Habanero in 2003, extensive catalogs of microseismicity were recovered. It is often assumed that shear failure of existing fractures is the main mechanism behind both the induced earthquakes and any permeability enhancement. This underpins a common notion, that the seismically active volume is also the stimulated reservoir. In this paper, we compute the density of earthquake hypocentersmore » and provide evidence that, under certain conditions, this spatiotemporal quantity is a reasonable proxy for pore pressure increase. We then apply an inverse modeling approach that uses the earthquake observations and a modified reservoir simulator to estimate the parameters of a permeability evolution relation. The regime implied by the data indicates that most permeability enhancement occurred very near to the wellbore and was not coincident with the bulk of the seismicity, whose volume was about two orders of magnitude larger. Thus, we conclude that, in some cases, it is possible for permeability enhancement and induced seismicity to be decoupled, in which case the seismically active volume is a poor indicator of the stimulated reservoir. Our results raise serious questions about the effectiveness of hydroshearing as a stimulation mechanism in EGS. Finally, this study extends our understanding of the complex processes linking earthquakes, fluid pressure, and permeability in both natural and engineered settings.« less
NASA Astrophysics Data System (ADS)
Feldman, J.; Dewers, T. A.; Heath, J. E.; Cather, M.; Mozley, P.
2016-12-01
Multiphase flow in clay-bearing sandstones of the Morrow Sandstone governs the efficiency of CO2 storage and enhanced oil recovery at the Farnsworth Unit, Texas. This formation is the target for enhanced oil recovery and injection of one million metric ton of anthropogenically-sourced CO2. The sandstone hosts eight major flow units that exhibit distinct microstructural characteristics due to diagenesis, including: "clean" macro-porosity; quartz overgrowths constricting some pores; ghost grains; intergranular porosity filled by microporous authigenic clay; and feldspar dissolution. We examine the microstructural controls on macroscale (core scale) relative permeability and capillary pressure behavior through: X-ray computed tomography, Robomet.3d, and focused ion beam-scanning electron microscopy imaging of the pore structure of the major flow units of the Morrow Sandstone; relative permeability and capillary pressure in the laboratory using CO2, brine, and oil at reservoir pressure and effective stress conditions. The combined data sets inform links between patterns of diagenesis and multiphase flow. These data support multiphase reservoir simulation and performance assessment by the Southwest Regional Partnership on Carbon Sequestration (SWP). Funding for this project is provided by the U.S. Department of Energy's National Energy Technology Laboratory through the SWP under Award No. DE-FC26-05NT42591. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.
ABSTRACT
We evaluated the safety of agents that enhance gene transfer by modulating paracellular permeability. Lactate dehydrogenase (LDH) and cytokine release were measured in polarized primary human airway epithelial (HAE) cells after luminal application of vehicle, ...
Abdelkader, Hamdy; Fathalla, Zeinab
2018-06-18
The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need. In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed. Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays. Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, P app for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. P app for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.
Permeability, storage and hydraulic diffusivity controlled by earthquakes
NASA Astrophysics Data System (ADS)
Brodsky, E. E.; Fulton, P. M.; Xue, L.
2016-12-01
Earthquakes can increase permeability in fractured rocks. In the farfield, such permeability increases are attributed to seismic waves and can last for months after the initial earthquake. Laboratory studies suggest that unclogging of fractures by the transient flow driven by seismic waves is a viable mechanism. These dynamic permeability increases may contribute to permeability enhancement in the seismic clouds accompanying hydraulic fracking. Permeability enhancement by seismic waves could potentially be engineered and the experiments suggest the process will be most effective at a preferred frequency. We have recently observed similar processes inside active fault zones after major earthquakes. A borehole observatory in the fault that generated the M9.0 2011 Tohoku earthquake reveals a sequence of temperature pulses during the secondary aftershock sequence of an M7.3 aftershock. The pulses are attributed to fluid advection by a flow through a zone of transiently increased permeability. Directly after the M7.3 earthquake, the newly damaged fault zone is highly susceptible to further permeability enhancement, but ultimately heals within a month and becomes no longer as sensitive. The observation suggests that the newly damaged fault zone is more prone to fluid pulsing than would be expected based on the long-term permeability structure. Even longer term healing is seen inside the fault zone of the 2008 M7.9 Wenchuan earthquake. The competition between damage and healing (or clogging and unclogging) results in dynamically controlled permeability, storage and hydraulic diffusivity. Recent measurements of in situ fault zone architecture at the 1-10 meter scale suggest that active fault zones often have hydraulic diffusivities near 10-2 m2/s. This uniformity is true even within the damage zone of the San Andreas fault where permeability and storage increases balance each other to achieve this value of diffusivity over a 400 m wide region. We speculate that fault zones may evolve to a preferred diffusivity in a dynamic equilibrium.
Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery
NASA Astrophysics Data System (ADS)
Matsumoto, Yu; Nichols, Joseph W.; Toh, Kazuko; Nomoto, Takahiro; Cabral, Horacio; Miura, Yutaka; Christie, R. James; Yamada, Naoki; Ogura, Tadayoshi; Kano, Mitsunobu R.; Matsumura, Yasuhiro; Nishiyama, Nobuhiro; Yamasoba, Tatsuya; Bae, You Han; Kataoka, Kazunori
2016-06-01
Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named ‘eruptions’) into the tumour interstitial space. We propose that ‘dynamic vents’ form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug.
Modeling the Hydrologic Processes of a Permeable Pavement System
A permeable pavement system can capture stormwater to reduce runoff volume and flow rate, improve onsite groundwater recharge, and enhance pollutant controls within the site. A new unit process model for evaluating the hydrologic performance of a permeable pavement system has be...
NASA Astrophysics Data System (ADS)
Nakajima, H.; Sawada, A.; Sugita, H.; Takeda, M.; Komai, T.; Zhang, M.
2006-12-01
Remediation of polluted soils and groundwater contaminated by heavy metals and non-aqueous phase liquids has been one of the challenging issues in the field of geo-environments. In-situ removal of the contaminants from low permeable soils, such as clay strata, is particularly difficult because of the low mobility, strong adsorption, and/or other various interactions within soils. Thus current remediation techniques, such as pump- and-treat method and even eletrokinetic method, generally suffer from low recovery rates and/or economically unacceptable long remediation periods. A perspective improvement in remediation technology is to couple the electrokinetic method with an application of acoustic waves. This so-called Electro-Acoustic Soil Decontamination (EASD) method has been proposed by Battelle Columbus Labs.(Muralidhara et al. 1990). Simultaneous application of an electric field and an acoustic field may produce a synergistic effect and result in further enhancement of water transport by electro-osmosis in principle, but there is still no fundamental data for the design of EASD method in practical applications. A number of investigations have shown that an application of acoustic waves can increase hydraulic conductivity and mobility of non-aqueous phase liquids in porous media. Most of the prior and ongoing researches in this area have been focused on increasing production from declining oil and gas reservoirs. During several field tests by the oil and gas industries, increases in oil production rates by 20% or more have been reported. However, underlying physical mechanisms for acoustically enhanced fluid transport are not adequately understood. In addition, majority of the past investigations has dealt with applications of large amplitude of acoustic waves to relatively permeable soils or fractured rocks, and there is little information if acoustic wave effectively enhances flow and contaminant transport for less permeable clayey soils. To evaluate the feasibility of the EASD method and to obtain the fundamental but important knowledge for the design of this method, it is first necessary to understand the effects of acoustic wave application on pore water flow behavior. A new apparatus is developed to investigate the effects of acoustic wave on hydraulic properties of soil sample. This test apparatus enables to confine a cylindrical specimen under hydrostatic pressure conditions and to apply acoustic wave simultaneously. Preliminary results associated with the effects of acoustic wave frequency on changes of permeability of kaolin clay samples are illustrated in this report. A program investigating the effects of electricity and pore water chemistry on efficiency of decontamination using the same samples is also ongoing and briefly presented. The two strategies for enhancing the efficiency of remediation for low permeable soils will be combined in the near future
Xue, Xiao-yan; Zhou, Ying; Chen, Ying-ying; Meng, Jing-ru; Jia, Min; Hou, Zheng; Bai, Hui; Mao, Xing-gang; Luo, Xiao-xing
2012-04-01
To find potential enhancers for facilitating the buccal delivery of insulin, a TR146 cell-culture model of buccal epithelium, cultured on commercially available insert plates, was used to evaluate the permeability-enhancing effects of several traditional and new types of chemical enhancers, including N-acetyl-L-cysteine (NAC), sodium deoxycholate (SDC), sodium nitroprusside (SNP), reduced glutathione (GSH), glutamine (Gln), chitosan (CS), L-arginine (Arg), 1-dodecylazacycloheptan-2-one (Azone), and soybean lecithin (SPC) (50 and 10 μg/mL respectively). Permeability studies were performed to determine the enhancing effects of these compounds on insulin permeation across the cell-culture model. The enhancing effects of the enhancers were assessed by calculating the apparent permeability coefficients and enhancement ratio. Cytotoxicity of the permeation enhancers at different concentrations was investigated by using the methylthiazolydiphenyl-tetrazolium bromide (MTT) assay. Results showed that 50 μg/mL of NAC, SDC, GSH, CS, Arg, Azone, SPC, SNP, and 10 μg/mL of SNP had a significant enhancing effect on promoting the transport of insulin across the TR146 cell model. MTT assays showed that 50 μg/mL of Gln, Azone, SDC, SNP, Arg, 10 μg/mL SDC, and Arg had obvious toxic effects on TR146 cells. Therefore, NAC, GSH, CS, SPC, and SNP appear to be safe, effective permeability enhancers that promote the transport of insulin across the TR146 cell-culture model of buccal epithelium and may be potential enhancers for buccal delivery of insulin with both low toxicity and high efficiency.
A multi-state magnetic memory dependent on the permeability of Metglas
DOE Office of Scientific and Technical Information (OSTI.GOV)
Petrie, J. R.; Wieland, K. A.; Timmerwilke, J. M.
A three-state magnetic memory was developed based on differences in the magnetic permeability of a soft ferromagnetic media, Metglas 2826MB (Fe{sub 40}Ni{sub 38}Mo{sub 4}B{sub 18}). By heating bits of a 250 nm thick Metglas film with 70–100 mW of laser power, we were able to tune the local microstructure, and hence, the permeability. Ternary memory states were created by using lower laser power to enhance the initial permeability through localized atomic rearrangement and higher power to reduce the permeability through crystallization. The permeability of the bits was read by detecting variations in an external 32 Oe probe field within 10 μm ofmore » the media via a magnetic tunnel junction read head. Compared to data based on remanent magnetization, these multi-permeability bits have enhanced insensitivity to unexpected field and temperature changes. We found that data was not corrupted after exposure to fields of 1 T or temperatures of 423 K, indicating the effectiveness of this multi-state approach for safely storing large amounts of data.« less
Recovery of ammonia and phosphate minerals from swine wastewater using gas-permeable membranes
USDA-ARS?s Scientific Manuscript database
Gas-permeable membrane technology is useful to recover ammonia from liquid manures. In this study, phosphorus (P) recovery via magnesium chloride precipitation was enhanced by combining it with ammonia recovery through gas-permeable membranes. Anaerobically digested swine effluent containing approx...
NASA Astrophysics Data System (ADS)
Furman-Haran, Edna; Margalit, Raanan; Grobgeld, Dov; Degani, Hadassa
1996-06-01
The mechanism of contrast enhancement of tumors using magnetic resonance imaging was investigated in MCF7 human breast cancer implanted in nude mice. Dynamic contrast-enhanced images recorded at high spatial resolution were analyzed by an image analysis method based on a physiological model, which included the blood circulation, the tumor, the remaining tissues, and clearance via the kidneys. This analysis enabled us to map in rapidly enhancing regions within the tumor, the capillary permeability factor (capillary permeability times surface area per voxel volume) and the fraction of leakage space. Correlation of these maps with T2-weighted spin echo images, with histopathology, and with immunohistochemical staining of endothelial cells demonstrated the presence of dense permeable microcapillaries in the tumor periphery and in intratumoral regions that surrounded necrotic loci. The high leakage from the intratumoral permeable capillaries indicated an induction of a specific angiogenic process associated with stress conditions that cause necrosis. This induction was augmented in tumors responding to tamoxifen treatment. Determination of the distribution and extent of this stress-induced angiogenic activity by contrast-enhanced MRI might be of diagnostic and of prognostic value.
Huang, Bei-Bei; Li, Guo-Feng; Luo, Jing-Hui; Duan, Lian; Nobuaki, Kishimoto; Akira, Yamamoto
2008-01-01
AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol significantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10% totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rebamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue significantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifically and the co-administration of C12 with rebamipide may also be very useful in local treatment. PMID:18756602
Examination of Blood-Brain Barrier (BBB) Integrity In A Mouse Brain Tumor Model
On, Ngoc; Mitchell, Ryan; Savant, Sanjot D.; Bachmeier, Corbin. J.; Hatch, Grant M.; Miller, Donald W.
2013-01-01
The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma (3LL) cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging (MRI) with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to 3H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a 2-fold increase in 3H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor. PMID:23184143
A stress-dependent model for reservoir stimulation in enhanced geothermal systems
NASA Astrophysics Data System (ADS)
Troiano, Antonio; Giulia Di Giuseppe, Maria; Troise, Claudia; De Natale, Giuseppe
2015-04-01
We present a procedure for testing the interpretation of the induced seismicity. The procedure is based on Coulomb stress changes induced by deep fluid injection during well stimulation, providing a way to estimate how the potential for seismic failure in different volumes of a geothermal reservoir might change due to the water injection. Coulomb stress changes appear to be the main cause for the induced seismicity during the water injection. These stress changes do not only result from changes in the pore pressure, but also from the whole change in the stress tensor at any point in the medium, which results from the pressure perturbations. The numerical procedure presented takes into account the permeability increase that is due to the induced stress changes. A conceptual model that links the induced stress tensor and the permeability modifications is considered to estimate the permeability change induced during the water injection. In this way, we can adapt the medium behavior to mechanical changes, in order to better evaluate the effectiveness of the stimulation process for the enhancement of the reservoir permeability, while also refining the reconstruction of the Coulomb stress change patterns. Numerical tests have been developed that consider a physical medium and a geometry of the system comparable with that of Soultz EGS site (Alsace, France). Tests considering a fixed permeability, both isotropic and anisotropic, indicate a general decrease in the pressure changes when an anisotropic permeability was considered, with respect to the isotropic case. A marked elongation of the coulomb stress change patterns in the regional load direction was retrieved. This effect is enforced when a stress-dependent permeability is taken into account. Permeability enhancement progressively enlarges the seismic volume in turns, while decreasing the pressure in the neighborhood of the bottom of the well. The use of stress-dependent permeability also improves the reconstruction of the observed seismicity pattern. In particular, the large maximum of the coulomb stress changes at the point of injection, which was already mitigated by the consideration of anisotropic permeability, appears further decreased in the new data. The improving of the correlation between the coulomb stress changes and the induced seismicity distribution supports the reliability and robustness of the main hypothesis of this study of the relationship between the induced stress tensor variation and the permeability enhancement. The use of stress-dependent permeability constitutes an important step towards the theoretical planning of stimulation procedures, and towards interpretation and mitigation of the induced seismicity.
NASA Astrophysics Data System (ADS)
Li, Z. W.; Yang, Z. H.
2016-03-01
Amorphous-membrane-filler composites have been fabricated using an infiltration method. The composites are able to significantly increase the permeability by 200%, as compared to general amorphous flake composites. SEM and magnetic measurement show that the amorphous flakes in membrane are in-plane arrangement. A model, which considers the effect of flake arrangement on demagnetizing factor Nd and permeability, is proposed. The effect of the arrangement of flakes is equivalent to an effective Nd, which is equal to 1/3 and zero for random and complete in-plane arrangements, respectively. Due to in-plane arrangement of amorphous flakes, the decreased Nd leads to significantly enhanced permeability for the amorphous-membrane-filler composites, based on the Maxwell-Garret mixing law.
Durymanov, Mikhail; Kamaletdinova, Tatiana; Lehmann, Sarah E; Reineke, Joshua
2017-09-10
Over the past few decades, enhanced permeability of tumor vasculature was actively exploited for targeted delivery of anticancer nanomedicines resulting in numerous pharmaceutical products. Formation of new immature and leaky vessels along with inflammatory remodeling of existing vessels accompany development of numerous diseases beyond cancer and present an opportunity for passive accumulation of intravenously administered nanomedicines in many pathological tissues. To date, applications of non-cancerous enhanced permeation have been relatively unexploited as target tissues and may create new therapy and prevention technologies for many disorders. Herein, we summarize the current knowledge on the nature of enhanced vascular permeability in multiple non-cancerous pathological tissues. We also discuss the clinical status of nanotherapeutics with selectivity based on passive accumulation in non-cancerous target tissues, their challenges, and prospects. Copyright © 2017 Elsevier B.V. All rights reserved.
Lucarini, Simone; Fagioli, Laura; Campana, Raffaella; Cole, Hannah; Duranti, Andrea; Baffone, Wally; Vllasaliu, Driton; Casettari, Luca
2016-10-01
Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi. Copyright © 2016 Elsevier B.V. All rights reserved.
Synergistic effect of EDTA and boric acid on corneal penetration of CS-088.
Kikuchi, Takayuki; Suzuki, Masahiko; Kusai, Akira; Iseki, Ken; Sasaki, Hitoshi
2005-02-16
In order to investigate the effects of EDTA and boric acid (EDTA/boric acid) on the corneal penetration of CS-088, an ophthalmic agent, the apparent permeability coefficient of CS-088 in the presence of EDTA/boric acid across the isolated corneal membranes of rabbits was measured using an in vitro penetration chamber system. FITC-dextran (M.W. 4400) and an electrical method based on membrane resistance were used to provide a quantitative assessment of the enhancing effect of EDTA/boric acid. The corneal penetration of CS-088 was significantly enhanced in the presence of EDTA/boric acid by approximately 1.6-fold. The permeability-enhancing effect of EDTA/boric acid was apparently synergistic and concentration-dependent on both EDTA and boric acid. The penetration of FITC-dextran, a paracellular marker, and electrical resistance of corneal membranes were not affected in the presence of EDTA/boric acid. Furthermore, no enhancing effect of EDTA/boric acid was observed in de-epithelialized corneas, although de-epithelialized corneas exhibited a markedly higher permeability of CS-088 that was 24-fold greater than that for intact corneas. In conclusion, EDTA/boric acid synergistically enhances the transcellular permeability of CS-088 in the outer layer but not in the inner layers of the corneal membrane.
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.
Sultan, Amal A; El-Gizawy, Sanaa A; Osman, Mohamed A; El Maghraby, Gamal M
2017-01-01
Mixed micelles provide promising strategy for enhancing dissolution and permeability of drugs. However, their fluid nature limited the stability of the loaded drug and hindered the development of stable oral dosage form. Accordingly, the objective was to develop solid self dispersing mixed micelle forming systems (MMFS) for enhanced dissolution and intestinal permeability of hydrochlorothiazide. Pseudoternary phase diagrams were constructed using sodium cholate, lecithin with either poloxamer 407 or PEG 4000 to determine the composition of MMFS. Both polymer free and poloxamer or PEG containing MMFS were prepared as homogenous matrices or as solid self dispersing powder. The later was developed by adsorption of MMFS on avicel-aerosil mixture. Differential scanning calorimetry provided an evidence for existence of hydrochlorothiazide as molecular dispersion in the MMFS. Dispersing polymer free, PEG 4000 or poloxamer based MMFS in aqueous medium produced micelles having size values of 119, 52.6 and 28nm, respectively. The zeta potential values were -61.8, -59.5 and -19.5mV for the same systems, respectively. Preparation of solid self dispersing MMFS enhanced the dissolution rate of hydrochlorothiazide. The intestinal absorption of hydrochlorothiazide from its aqueous solution and polymer incorporating mixed micellar systems was monitored using in situ rabbit intestinal perfusion technique. The permeability results showed a clear trend for enhanced membrane transport of the drug after being incorporated into poloxamer containing mixed micellar system. The study thus introduced a versatile easily formulated solid self dispersing system with high potential for solving the dissolution and permeability problems of class IV drugs. Copyright © 2016 Elsevier B.V. All rights reserved.
Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L
2010-08-02
Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-naphthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K(11(aq))) of 388 M(-1) for ZHE-HNAP and 2.91 M(-1) for GO-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 10(-6) cm/s) was observed in the presence of 6-24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 P(app) versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (P(eff)) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this work presents a novel approach to enable the oral delivery of highly polar antiviral drugs, and provides new insights into the underlying mechanisms governing the success or failure of the ion-pairing strategy to increase oral absorption.
Moghimipour, Eskandar; Tabassi, Sayyed Abolghassem Sajadi; Ramezani, Mohammad; Handali, Somayeh; Löbenberg, Raimar
2016-01-01
The aim of this study was to investigate the influence of absorption enhancers in the uptake of hydrophilic compounds. The permeation of the two hydrophilic drug models gentamicin and 5 (6)-carboxyfluorescein (CF) across the brush border membrane vesicles and Caco-2 cell lines were evaluated using total saponins of Acanthophyllum squarrosum, Quillaja saponaria, sodium lauryl sulfate, sodium glycocholate, sodium taurodeoxycholate, and Tween 20 as absorption enhancers. Transepithelial electrical resistance (TEER) measurement was utilized to assess the paracellular permeability of cell lines. Confocal laser scanning microscopy (CLSM) was performed to obtain images of the distribution of CF in Caco-2 cells. These compounds were able to loosen tight junctions, thus increasing paracellular permeability. CLSM confirmed the effect of these absorption enhancers on CF transport across Caco-2 lines and increased the Caco-2 permeability via transcellular route. It was also confirmed that the decrease in TEER was transient and reversible after removal of permeation enhancers. PMID:27429925
Poromechanical response of naturally fractured sorbing media
NASA Astrophysics Data System (ADS)
Kumar, Hemant
The injection of CO2 in coal seams has been utilized for enhanced gas recovery and potential CO2 sequestration in unmineable coal seams. It is advantageous because as it enhances the production and significant volumes of CO2 may be stored simultaneously. The key issues for enhanced gas recovery and geologic sequestration of CO2 include (1) Injectivity prediction: The chemical and physical processes initiated by the injection of CO2 in the coal seam leads to permeability/porosity changes (2) Up scaling: Development of full scale coupled reservoir model which may predict the enhanced production, associated permeability changes and quantity of sequestered CO2. (3) Reservoir Stimulation: The coalbeds are often fractured and proppants are placed into the fractures to prevent the permeability reduction but the permeability evolution in such cases is poorly understood. These issues are largely governed by dynamic coupling of adsorption, fluid exchange, transport, water content, stress regime, fracture geometry and physiomechanical changes in coals which are triggered by CO 2 injection. The understanding of complex interactions in coal has been investigated through laboratory experiments and full reservoir scale models are developed to answer key issues. (Abstract shortened by ProQuest.).
Permeability enhancement by shock cooling
NASA Astrophysics Data System (ADS)
Griffiths, Luke; Heap, Michael; Reuschlé, Thierry; Baud, Patrick; Schmittbuhl, Jean
2015-04-01
The permeability of an efficient reservoir, e.g. a geothermal reservoir, should be sufficient to permit the circulation of fluids. Generally speaking, permeability decreases over the life cycle of the geothermal system. As a result, is usually necessary to artificially maintain and enhance the natural permeability of these systems. One of the methods of enhancement -- studied here -- is thermal stimulation (injecting cold water at low pressure). This goal of this method is to encourage new thermal cracks within the reservoir host rocks, thereby increasing reservoir permeability. To investigate the development of thermal microcracking in the laboratory we selected two granites: a fine-grained (Garibaldi Grey granite, grain size = 0.5 mm) and a course-grained granite (Lanhelin granite, grain size = 2 mm). Both granites have an initial porosity of about 1%. Our samples were heated to a range of temperatures (100-1000 °C) and were either cooled slowly (1 °C/min) or shock cooled (100 °C/s). A systematic microstructural (2D crack area density, using standard stereological techniques, and 3D BET specific surface area measurements) and rock physical property (porosity, P-wave velocity, uniaxial compressive strength, and permeability) analysis was undertaken to understand the influence of slow and shock cooling on our reservoir granites. Microstructurally, we observe that the 2D crack surface area per unit volume and the specific surface area increase as a result of thermal stressing, and, for the same maximum temperature, crack surface area is higher in the shock cooled samples. This observation is echoed by our rock physical property measurements: we see greater changes for the shock cooled samples. We can conclude that shock cooling is an extremely efficient method of generating thermal microcracks and modifying rock physical properties. Our study highlights that thermal treatments are likely to be an efficient method for the "matrix" permeability enhancement of granitic geothermal reservoirs.
Polymer as Permeability Modifier in Porous Media
NASA Astrophysics Data System (ADS)
Parsa, S.; Weitz, D.
2017-12-01
Polymer flow through porous media is of particular interest in applications such as enhanced oil recovery and ground water remediation. We measure the effects of polymer flow on the permeability and local velocity distribution of a single phase flow in 3D micromodel of porous media using confocal microscopy and bulk permeability measurement. Our measurements show considerable reduction in permeability and increased velocity fluctuations with fluid velocities being diverted in some pores after polymer flow. We also find that the average velocity in the medium at constant imposed flow rate scales with the inverse square root of permeability.
NASA Astrophysics Data System (ADS)
Min, K. B.; Park, S.; Xie, L.; Kim, K. I.; Yoo, H.; Kim, K. Y.; Choi, J.; Yoon, K. S.; Yoon, W. S.; Lee, T. J.; Song, Y.
2017-12-01
Enhanced Geothermal System (EGS) relies on sufficient and irreversible enhancement of reservoir permeability through hydraulic stimulation and possibility of such desirable change of permeability is an open question that can undermine the universality of EGS concept. We report results of first hydraulic stimulation campaign conducted in two deep boreholes in fractured granodiorite geothermal reservoir in Pohang, Korea. Borehole PX-1, located at 4.22 km, was subjected to the injection of 3,907 m3 with flow rate of up to 18 kg/s followed by bleeding off of 1,207 m3. The borehole PX-2, located at 4.35 km, was subjected to the injection of 1,970 m3 with flow rate of up to 46 kg/sIn PX-1, a sharp distinct decline of wellhead pressure was observed at around 16 MPa of wellhead pressure which was similar to the predicted injection pressure to induce hydraulic shearing. Injectivity interpretation before and after the hydraulic shearing indicates that permanent increase of permeability was achieved by a factor of a few. In PX-2, however, injectivity was very small and hydraulic shearing was not observed due possibly to the near wellbore damage made by the remedying process of lost circulation such as using lost circulation material during drilling. Flow rate of larger than 40 kg/s was achieved at very high well head pressure of nearly 90 MPa. Hydraulic jacking, that is reversible opening and closure of fracture with change of injection pressure, was clearly observed. Although sharp increase of permeability due to fracture opening was achieved with elevated injection pressure, the increased permeability was reversed with decreased injection pressure.Two contrasting response observed in the same reservoir at two different boreholes which is apart only 600 m apart provide important implication that can be used for the stimulation strategy for EGS.This work was supported by the New and Renewable Energy Technology Development Program of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) through a grant funded by the Korean Government's Ministry of Trade, Industry & Energy (No. 20123010110010).
Enhancement of extracellular electron transfer and bioelectricity output by synthetic porin.
Yong, Yang-Chun; Yu, Yang-Yang; Yang, Yun; Liu, Jing; Wang, Jing-Yuan; Song, Hao
2013-02-01
The microbial fuel cell (MFC), is a promising environmental biotechnology for harvesting electricity energy from organic wastes. However, low bacterial membrane permeability of electron shuttles is a limiting factor that restricts the electron shuttle-mediated extracellular electron transfer (EET) from bacteria to electrodes, thus the electricity power output of MFCs. To this end, we heterologously expressed a porin protein OprF from Pseudomonas aeruginosa PAO1 into Escherichia coli, which dramatically increased its membrane permeability, delivering a much higher current output in MFCs than its parental strain (BL21). We found that the oprF-expression strain showed more efficient EET than its parental strain. More strikingly, the enhanced membrane permeability also rendered the oprF-expression strain an efficient usage of riboflavin as the electron shuttle, whereas its parental strain was incapable of. Our results substantiated that membrane permeability is crucial for the efficient EET, and indicated that the expression of synthetic porins could be an efficient strategy to enhance bioelectricity generation by microorganisms (including electrogenic bacteria) in MFCs. Copyright © 2012 Wiley Periodicals, Inc.
Duration of ultrasound-mediated enhanced plasma membrane permeability.
Lammertink, Bart; Deckers, Roel; Storm, Gert; Moonen, Chrit; Bos, Clemens
2015-03-30
Ultrasound (US) induced cavitation can be used to enhance the intracellular delivery of drugs by transiently increasing the cell membrane permeability. The duration of this increased permeability, termed temporal window, has not been fully elucidated. In this study, the temporal window was investigated systematically using an endothelial- and two breast cancer cell lines. Model drug uptake was measured as a function of time after sonication, in the presence of SonoVue™ microbubbles, in HUVEC, MDA-MB-468 and 4T1 cells. In addition, US pressure amplitude was varied in MDA-MB-468 cells to investigate its effect on the temporal window. Cell membrane permeability of HUVEC and MDA-MB-468 cells returned to control level within 1-2 h post-sonication, while 4T1 cells needed over 3h. US pressure affected the number of cells with increased membrane permeability, as well as the temporal window in MDA-MB-468 cells. This study shows that the duration of increased membrane permeability differed between the cell lines and US pressures used here. However, all were consistently in the order of 1-3 h after sonication. Copyright © 2014 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Jihoon; Moridis, George J.
We investigate coupled flow and geomechanics in gas production from extremely low permeability reservoirs such as tight and shale gas reservoirs, using dynamic porosity and permeability during numerical simulation. In particular, we take the intrinsic permeability as a step function of the status of material failure, and the permeability is updated every time step. We consider gas reservoirs with the vertical and horizontal primary fractures, employing the single and dynamic double porosity (dual continuum) models. We modify the multiple porosity constitutive relations for modeling the double porous continua for flow and geomechanics. The numerical results indicate that production of gasmore » causes redistribution of the effective stress fields, increasing the effective shear stress and resulting in plasticity. Shear failure occurs not only near the fracture tips but also away from the primary fractures, which indicates generation of secondary fractures. These secondary fractures increase the permeability significantly, and change the flow pattern, which in turn causes a change in distribution of geomechanical variables. From various numerical tests, we find that shear failure is enhanced by a large pressure drop at the production well, high Biot's coefficient, low frictional and dilation angles. Smaller spacing between the horizontal wells also contributes to faster secondary fracturing. When the dynamic double porosity model is used, we observe a faster evolution of the enhanced permeability areas than that obtained from the single porosity model, mainly due to a higher permeability of the fractures in the double porosity model. These complicated physics for stress sensitive reservoirs cannot properly be captured by the uncoupled or flow-only simulation, and thus tightly coupled flow and geomechanical models are highly recommended to accurately describe the reservoir behavior during gas production in tight and shale gas reservoirs and to smartly design production scenarios.« less
Kim, Jihoon; Moridis, George J.
2014-12-01
We investigate coupled flow and geomechanics in gas production from extremely low permeability reservoirs such as tight and shale gas reservoirs, using dynamic porosity and permeability during numerical simulation. In particular, we take the intrinsic permeability as a step function of the status of material failure, and the permeability is updated every time step. We consider gas reservoirs with the vertical and horizontal primary fractures, employing the single and dynamic double porosity (dual continuum) models. We modify the multiple porosity constitutive relations for modeling the double porous continua for flow and geomechanics. The numerical results indicate that production of gasmore » causes redistribution of the effective stress fields, increasing the effective shear stress and resulting in plasticity. Shear failure occurs not only near the fracture tips but also away from the primary fractures, which indicates generation of secondary fractures. These secondary fractures increase the permeability significantly, and change the flow pattern, which in turn causes a change in distribution of geomechanical variables. From various numerical tests, we find that shear failure is enhanced by a large pressure drop at the production well, high Biot's coefficient, low frictional and dilation angles. Smaller spacing between the horizontal wells also contributes to faster secondary fracturing. When the dynamic double porosity model is used, we observe a faster evolution of the enhanced permeability areas than that obtained from the single porosity model, mainly due to a higher permeability of the fractures in the double porosity model. These complicated physics for stress sensitive reservoirs cannot properly be captured by the uncoupled or flow-only simulation, and thus tightly coupled flow and geomechanical models are highly recommended to accurately describe the reservoir behavior during gas production in tight and shale gas reservoirs and to smartly design production scenarios.« less
NASA Astrophysics Data System (ADS)
Kobayashi, Hisataka; Choyke, Peter L.
2016-06-01
To date, the delivery of nano-sized therapeutic agents to cancers largely relies on enhanced permeability and retention (EPR) effects that are caused by the leaky nature of cancer vasculature. However, nano-sized agents delivered in this way have demonstrated limited success in oncology due to the relatively small magnitude of the EPR effect. For achieving superior delivery of nano-sized agents, super-enhanced permeability and retention (SUPR) effects are needed. Near infrared photo-immunotherapy (NIR-PIT) is a recently reported therapy that treats tumors with light therapy and subsequently causes an increase in nano-drug delivery up to 24-fold compared with untreated tumors in which only the EPR effect is present. SUPR effects could enhance delivery into tumor beds of a wide variety of nano-sized agents including particles, antibodies, and protein binding small molecular agents. Therefore, taking advantage of the SUPR effects after NIR-PIT may be a promising avenue to utilize a wide variety of nano-drugs in a highly effective manner.
Gundogdu, E; Alvarez, I Gonzalez; Karasulu, E
2011-01-01
Fexofenadine (FEX) has high solubility and low permeability (BCS, Class III). In this work, novel FEX loaded water in oil microemulsion (w/o) was designed to improve bioavailability and compared with Fexofen® syrup in in vitro and in vivo studies. In addition, pharmacokinetic parameters in permeability studies were estimated by using WinNonLin software program. w/o microemulsion system was optimized using a pseudoternary phase diagram, composed of span 80/lutrol F 68 (9.5:0.5 w/w), oleic acide, isopropyl alcohol and water as surfactant mixture; oil and cosurfactant was developed for oral drug delivery. w/o microemulsion systems were characterized by phase behavior, particle size, viscosity and solubilization capacity. In vitro studies were studied using Caco-2 cell monolayer. Pharmacokinetic parameters of w/o microemulsion were investigated in rabbits and compared to Fexofen® syrup. Fexofen® syrup and microemulsion were administered by oral gavage at 6 mg/kg of the same concentration. The experimental results indicated that microemulsion (HLB = 5.53) formed nanometer sized droplets (33.29 ± 1.76) and had good physical stability. This microemulsion increased the oral bioavailability of FEX which was highly water-soluble but fairly impermeable. The relative bioavailability of FEX microemulsion was about 376.76% compared with commercial syrup in rabbits. In vitro experiments were further employed for the enhanced effect of the microemulsion for FEX. These results suggest that novel w/o microemulsion plays an important role in enhancing oral bioavailability of low permeability drugs. PMID:21904453
Udegbunam, E.O.
1991-01-01
This paper presents a FORTRAN program for the determination of two-phase relative permeabilities from unsteady-state displacement data with capillary pressure terms included. The interpretative model employed in this program combines the simultaneous solution of a variant of the fractional flow equation which includes a capillary pressure term and an integro-differential equation derived from Darcy's law without assuming the simplified Buckley-Leverett flow. The incorporation of capillary pressure in the governing equations dispenses with the high flowrate experimental requirements normally employed to overcome capillarity effects. An illustrative example is presented herein which implements this program for the determination of oil/water relative permeabilities from a sandstone core sample. Results obtained compares favorably with results previously given in the literature. ?? 1991.
NASA Astrophysics Data System (ADS)
Huenges, Ernst; Trautwein, Ute; Legarth, Björn; Zimmermann, Günter
2006-10-01
The Rotliegend of the North German basin is the target reservoir of an interdisciplinary investigation program to develop a technology for the generation of geothermal electricity from low-enthalpy reservoirs. An in situ downhole laboratory was established in the 4.3 km deep well Groβ Schönebeck with the purpose of developing appropriate stimulation methods to increase permeability of deep aquifers by enhancing or creating secondary porosity and flow paths. The goal is to learn how to enhance the inflow performance of a well from a variety of rock types in low permeable geothermal reservoirs. A change in effective stress due to fluid pressure was observed to be one of the key parameters influencing flow properties both downhole and in laboratory experiments on reservoir rocks. Fluid pressure variation was induced using proppant-gel-frac techniques as well as waterfrac techniques in several different new experiments in the borehole. A pressure step test indicates generation and extension of multiple fractures with closure pressures between 6 and 8.4 MPa above formation pressure. In a 24-hour production test 859 m3 water was produced from depth indicating an increase of productivity in comparison with former tests. Different depth sections and transmissibility values were observed in the borehole depending on fluid pressure. In addition, laboratory experiments were performed on core samples from the sandstone reservoir under uniaxial strain conditions, i.e., no lateral strain, constant axial load. The experiments on the borehole and the laboratory scale were realized on the same rock types under comparable stress conditions with similar pore pressure variations. Nevertheless, stress dependences of permeability are not easy to compare from scale to scale. Laboratory investigations reflect permeability variations due to microstructural heterogeneities and the behavior in the borehole is dominated by the generation of connections to large-scale structural patterns.
Hou, Maihua; Sun, Richard; Hupe, Melanie; Kim, Peggy L.; Park, Kyungho; Crumrine, Debra; Lin, Tzu-kai; Santiago, Juan Luis; Mauro, Theodora M.; Elias, Peter M.; Man, Mao-Qiang
2013-01-01
The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, Chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In the present study, we first determined whether topical apigenin positively influences permeability barrier homeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice-daily for 9 days. At the end of treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homeostasis after tape stripping, though basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were up-regulated by apigenin. Finally, both CAMP and mBD3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels, and impaired antimicrobial defenses, such as atopic dermatitis. PMID:23489424
Gleeson, Tom; Ingebritsen, Steven E.
2016-01-01
Permeability is the primary control on fluid flow in the Earth’s crust and is key to a surprisingly wide range of geological processes, because it controls the advection of heat and solutes and the generation of anomalous pore pressures. The practical importance of permeability – and the potential for large, dynamic changes in permeability – is highlighted by ongoing issues associated with hydraulic fracturing for hydrocarbon production (“fracking”), enhanced geothermal systems, and geologic carbon sequestration. Although there are thousands of research papers on crustal permeability, this is the first book-length treatment. This book bridges the historical dichotomy between the hydrogeologic perspective of permeability as a static material property and the perspective of other Earth scientists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions.
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.
Kinoshita, Ryo; Ishima, Yu; Chuang, Victor T G; Nakamura, Hideaki; Fang, Jun; Watanabe, Hiroshi; Shimizu, Taro; Okuhira, Keiichiro; Ishida, Tatsuhiro; Maeda, Hiroshi; Otagiri, Masaki; Maruyama, Toru
2017-09-01
In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane ® ). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.
Trench infiltration for managed aquifer recharge to permeable bedrock
Heilweil, V.M.; Watt, D.E.
2011-01-01
Managed aquifer recharge to permeable bedrock is increasingly being utilized to enhance resources and maintain sustainable groundwater development practices. One such target is the Navajo Sandstone, an extensive regional aquifer located throughout the Colorado Plateau of the western United States. Spreading-basin and bank-filtration projects along the sandstone outcrop's western edge in southwestern Utah have recently been implemented to meet growth-related water demands. This paper reports on a new cost-effective surface-infiltration technique utilizing trenches for enhancing managed aquifer recharge to permeable bedrock. A 48-day infiltration trench experiment on outcropping Navajo Sandstone was conducted to evaluate this alternative surface-spreading artificial recharge method. Final infiltration rates through the bottom of the trench were about 0.5 m/day. These infiltration rates were an order of magnitude higher than rates from a previous surface-spreading experiment at the same site. The higher rates were likely caused by a combination of factors including the removal of lower permeability soil and surficial caliche deposits, access to open vertical sandstone fractures, a reduction in physical clogging associated with silt and biofilm layers, minimizing viscosity effects by maintaining isothermal conditions, minimizing chemical clogging caused by carbonate mineral precipitation associated with algal photosynthesis, and diminished gas clogging associated with trapped air and biogenic gases. This pilot study illustrates the viability of trench infiltration for enhancing surface spreading of managed aquifer recharge to permeable bedrock. ?? 2010.
Long-term thermal effects on injectivity evolution during CO 2 storage
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vilarrasa, Victor; Rinaldi, Antonio P.; Rutqvist, Jonny
Carbon dioxide (CO 2 ) is likely to reach the bottom of injection wells at a colder temperature than that of the storage formation, causing cooling of the rock. This cooling, together with overpressure, tends to open up fractures, which may enhance injectivity. Here, we investigate cooling effects on injectivity enhancement by modeling the In Salah CO 2 storage site and a theoretical, long-term injection case. We use stress-dependent permeability functions that predict an increase in permeability as the effective stress acting normal to fractures decreases. Normal effective stress can decrease either due to overpressure or cooling. We calibrate ourmore » In Salah model, which includes a fracture zone perpendicular to the well, obtaining a good fitting with the injection pressure measured at KB-502 and the rapid CO 2 breakthrough that occurred at the observation well KB-5 located 2 km away from the injection well. CO 2 preferentially advances through the fracture zone, which becomes two orders of magnitude more permeable than the rest of the reservoir. Nevertheless, the effect of cooling on the long-term injectivity enhancement is limited in pressure dominated storage sites, like at In Salah, because most of the permeability enhancement is due to overpressure. But, thermal effects enhance injectivity in cooling dominated storage sites, which may decrease the injection pressure by 20%, saving a significant amount of compression energy all over the duration of storage projects. Overall, our simulation results show that cooling has the potential to enhance injectivity in fractured reservoirs.« less
Long-term thermal effects on injectivity evolution during CO 2 storage
Vilarrasa, Victor; Rinaldi, Antonio P.; Rutqvist, Jonny
2017-08-22
Carbon dioxide (CO 2 ) is likely to reach the bottom of injection wells at a colder temperature than that of the storage formation, causing cooling of the rock. This cooling, together with overpressure, tends to open up fractures, which may enhance injectivity. Here, we investigate cooling effects on injectivity enhancement by modeling the In Salah CO 2 storage site and a theoretical, long-term injection case. We use stress-dependent permeability functions that predict an increase in permeability as the effective stress acting normal to fractures decreases. Normal effective stress can decrease either due to overpressure or cooling. We calibrate ourmore » In Salah model, which includes a fracture zone perpendicular to the well, obtaining a good fitting with the injection pressure measured at KB-502 and the rapid CO 2 breakthrough that occurred at the observation well KB-5 located 2 km away from the injection well. CO 2 preferentially advances through the fracture zone, which becomes two orders of magnitude more permeable than the rest of the reservoir. Nevertheless, the effect of cooling on the long-term injectivity enhancement is limited in pressure dominated storage sites, like at In Salah, because most of the permeability enhancement is due to overpressure. But, thermal effects enhance injectivity in cooling dominated storage sites, which may decrease the injection pressure by 20%, saving a significant amount of compression energy all over the duration of storage projects. Overall, our simulation results show that cooling has the potential to enhance injectivity in fractured reservoirs.« less
Regulation of Epithelial Cell Permeability by Nanostructured Thin Films
NASA Astrophysics Data System (ADS)
Stewart, Tarianna V.
Epithelia form barriers that regulate the movement of water, ions and molecules from one part of an organ to another. Facilitated transepithelial transport is important to enable drug delivery. Using human colon carcinoma (Caco-2) epithelial cells as a model, I found that contact with patterned nanostructured films (NSFs) enhanced the transepithelial transport of several different macromolecules without using chemical permeation agents. To determine the maximum paracellular permeability through tight junctions (TJs) I modified a calcium-"switch" model, as measured by the diffusion rate for all of the probes examined when media was changed from standard (20 mM) to low (10 microM) calcium. I then compared the permeability of Caco-2 cells in contact with NSFs to the maximum paracellular permeability of cells without NSFs at baseline. Caco-2 cells stimulated with NSFs showed an enhanced level of apical to basolateral transport for intact IgG compared to maximum paracellular permeability. However for the other probes examined, the paracellular permeability induced by NSFs was less than the maximum paracellular permeability of cells. These findings suggest that Caco-2 cells in contact with NSFs induce the specific, active transport of IgG from the apical to the basolateral cell surface of the epithelium. A series of experiments demonstrated the presence of so-called "neonatal" Fc receptors (FcRn) in Caco-2 cells and that these mediated the transcytosis of IgG across the cells. Moreover, contact with NSFs also enhanced paracellular transport, as determined by changes in TJ morphology and decreased transepithelial resistance (TER). To better understand the effects of NSFs on paracellular transport, we measured changes in matrix-metalloendoprotease (MMP) expression and activity was examined. MMP-2 and MMP-9 were upregulated by contact with NSFs. Roles for MMPs in regulating the effects of NSFs on epithelial cells are discussed. Thus, NSFs specifically enhance the transepithelial transport of agents in a substrate dependent manner utilizing both the transcellular and paracellular routes, suggesting that NSF-based devices are critical to developing a tunable drug delivery system.
Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M.; Mariani, John N.; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S.
2015-01-01
In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood–brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood–brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood–brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood–brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood–brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood–brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood–brain barrier breakdown. PMID:25805644
Ahn, S S; Kim, S H; Lee, J E; Ahn, K J; Kim, D J; Choi, H S; Kim, J; Shin, N-Y; Lee, S-K
2015-02-01
BBB disruption after acute ischemic stroke and subsequent permeability increase may be enhanced by reperfusion. Agmatine has been reported to attenuate BBB disruption. Our aim was to evaluate the effects of agmatine on BBB stabilization in a rat model of transient cerebral ischemia by using permeability dynamic contrast-enhanced MR imaging at early stages and subsequently to demonstrate the feasibility of dynamic contrast-enhanced MR imaging for the investigation of new therapies. Thirty-four male Sprague-Dawley rats were subjected to transient MCA occlusion for 90 minutes. Immediately after reperfusion, agmatine (100 mg/kg) or normal saline was injected intraperitoneally into the agmatine-treated group (n = 17) or the control group, respectively. MR imaging was performed after reperfusion. For quantitative analysis, regions of interest were defined within the infarct area, and values for volume transfer constant, rate transfer coefficient, volume fraction of extravascular extracellular space, and volume fraction of blood plasma were obtained. Infarct volume, infarct growth, quantitative imaging parameters, and numbers of factor VIII-positive cells after immunohistochemical staining were compared between control and agmatine-treated groups. Among the permeability parameters, volume transfer constant and volume fraction of extravascular extracellular space were significantly lower in the agmatine-treated group compared with the control group (0.05 ± 0.02 minutes(-1) versus 0.08 ± 0.03 minute(-1), P = .012, for volume transfer constant and 0.12 ± 0.06 versus 0.22 ± 0.15, P = .02 for volume fraction of extravascular extracellular space). Other permeability parameters were not significantly different between the groups. The number of factor VIII-positive cells was less in the agmatine-treated group than in the control group (3-fold versus 4-fold, P = .037). In ischemic stroke, agmatine protects the BBB, which can be monitored in vivo by quantification of permeability by using dynamic contrast-enhanced MR imaging. Therefore, dynamic contrast-enhanced MR imaging may serve as a potential imaging biomarker for assessing the BBB stabilization properties of pharmacologic agents. © 2015 by American Journal of Neuroradiology.
Li, Hai-juan; Yang, Long-long; Tian, Wei; Liu, Jun-ju; Xie, Xue-jun; Guo, Guo-zhen
2012-03-01
To establish the inner blood-retinal barrier (BRB) model in vitro by co-culturing RF/6A cells and C6 cells and to investigate the effects of EMP (200 kV/m, 200 pulses) exposure on the permeability of the inner BRB model in vitro. RF/6A cells and C6 cells were co-cultured on transwell, and the characteristic of the inner BRB model was assessed by detecting transendothelial electrical resistance (TEER) and the permeability of horseradish peroxidase (HRP). The co-cultured model was exposed or sham exposed to the EMP (200 kV/m 200 pulses) for 0.5, 3, 6, 12, 24 h in vitro, then TEER and the permeability of HRP were measured for studying the effects of EMP on the permeability of inner BRB model in vitro. TEER value (145 Ωcm(2)) of the co-culturing inner BRB model significantly increased, as compared to that of RF/6A cells alone model (P < 0.05) on the 6th day after inoculation. There was significant difference of permeability of HRP between the co-culturing inner BRB model and RF/6A cells alone model (P < 0.05). The ability of inhibiting large molecular materials in the co-culturing inner BRB model enhanced. The TEER value decreased and the permeability of HRP increased as compared to the sham group at 0.5, 3, 6 h after the exposure. The inner BRB model by co-culturing RF/6A cells and C6 cells in vitro is efficient and suitable to study the alterations of the restricted permeability function of the inner BRB. EMP (200 kV/m for 200 pulses) could induce the enhanced permeability of the inner BRB model in vitro.
Dopamine enhances duodenal epithelial permeability via the dopamine D5 receptor in rodent.
Feng, X-Y; Zhang, D-N; Wang, Y-A; Fan, R-F; Hong, F; Zhang, Y; Li, Y; Zhu, J-X
2017-05-01
The intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D 1 (D 1 R) and D 5 (D 5 R), but whether D1-like receptors influence the duodenal permeability is unclear. FITC-dextran permeability, short-circuit current (I SC ), Western blot, immunohistochemistry and ELISA were used in human D 5 R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study. Dopamine induced a downward deflection in I SC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D 5 R, but not D 1 R, was observed in the duodenum of control rat. In human D 5 R knock-in transgenic mice, duodenal mucosa displayed an increased basal I SC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D 5 R knock-down transgenic mice manifested a decreased basal I SC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats. This study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D 5 R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
The transition from brittle faulting to cataclastic flow: Permeability evolution
NASA Astrophysics Data System (ADS)
Zhu, Wenlu; Wong, Teng-Fong
1997-02-01
Triaxial compression experiments were conducted to investigate influences of stress and failure mode on axial permeability of five sandstones with porosities ranging from 15% to 35%. In the cataclastic flow regime, permeability and porosity changes closely track one another. A drastic decrease in permeability was triggered by the onset of shear-enhanced compaction caused by grain crushing and pore collapse. The compactive yield stress C* maps out a boundary in stress space separating two different types of permeability evolution. Before C* is attained, permeability and porosity both decrease with increasing effective mean stress, but they are independent of deviatoric stresses. However, with loading beyond C*, both permeability and porosity changes are strongly dependent on the deviatoric and effective mean stresses. In the brittle faulting regime, permeability and porosity changes are more complex. Before the onset of shear-induced dilation C', both permeability and porosity decrease with increasing effective mean stress. Beyond C', permeability may actually decrease in a dilating rock prior to brittle failure. After the peak stress has been attained, the development of a relatively impermeable shear band causes an accelerated decrease of permeability. Permeability evolution in porous sandstones is compared with that in low-porosity crystalline rocks. A conceptual model for the coupling of deformation and fluid transport is proposed in the form of a deformation-permeability map.
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.
Fault Zone Permeability Decrease Following Large Earthquakes in a Hydrothermal System
NASA Astrophysics Data System (ADS)
Shi, Zheming; Zhang, Shouchuan; Yan, Rui; Wang, Guangcai
2018-02-01
Seismic wave shaking-induced permeability enhancement in the shallow crust has been widely observed. Permeability decrease, however, is seldom reported. In this study, we document coseismic discharge and temperature decrease in a hot spring following the 1996 Lijiang Mw 7.0 and the 2004 Mw 9.0 earthquakes in the Balazhang geothermal field. We use three different models to constrain the permeability change and the mechanism of coseismic discharge decrease, and we use an end-member mixing model for the coseismic temperature change. Our results show that the earthquake-induced permeability decrease in the fault zone reduced the recharge from deep hot water, which may be the mechanism that explains the coseismic discharge and temperature responses. The changes in the hot spring response reflect the dynamic changes in the hydrothermal system; in the future, the earthquake-induced permeability decrease should be considered when discussing controls on permeability.
Assessment of Pronghorn movements and strategies to promote highway permeability : US Highway 89.
DOT National Transportation Integrated Search
2010-05-01
Pronghorn (Antilocapra americana) movements were investigated with Global Position System (GPS) : telemetry from 2007 to 2008 along a 28-mile stretch of U.S. Highway 89 in northern Arizona to develop : strategies to enhance permeability with future h...
Towards cavitation-enhanced permeability in blood vessel on a chip
NASA Astrophysics Data System (ADS)
De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.
2017-08-01
The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.
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.
Pneumatic fracturing of low permeability media
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schuring, J.R.
1996-08-01
Pneumatic fracturing of soils to enhance the removal and treatment of dense nonaqueous phase liquids is described. The process involves gas injection at a pressure exceeding the natural stresses and at a flow rate exceeding the permeability of the formation. The paper outlines geologic considerations, advantages and disadvantages, general technology considerations, low permeability media considerations, commercial availability, efficiency, and costs. Five case histories of remediation using pneumatic fracturing are briefly summarized. 11 refs., 2 figs., 1 tab.
Vakil, P; Ansari, S A; Cantrell, C G; Eddleman, C S; Dehkordi, F H; Vranic, J; Hurley, M C; Batjer, H H; Bendok, B R; Carroll, T J
2015-05-01
Pathological changes in the intracranial aneurysm wall may lead to increases in its permeability; however the clinical significance of such changes has not been explored. The purpose of this pilot study was to quantify intracranial aneurysm wall permeability (K(trans), VL) to contrast agent as a measure of aneurysm rupture risk and compare these parameters against other established measures of rupture risk. We hypothesized K(trans) would be associated with intracranial aneurysm rupture risk as defined by various anatomic, imaging, and clinical risk factors. Twenty-seven unruptured intracranial aneurysms in 23 patients were imaged with dynamic contrast-enhanced MR imaging, and wall permeability parameters (K(trans), VL) were measured in regions adjacent to the aneurysm wall and along the paired control MCA by 2 blinded observers. K(trans) and VL were evaluated as markers of rupture risk by comparing them against established clinical (symptomatic lesions) and anatomic (size, location, morphology, multiplicity) risk metrics. Interobserver agreement was strong as shown in regression analysis (R(2) > 0.84) and intraclass correlation (intraclass correlation coefficient >0.92), indicating that the K(trans) can be reliably assessed clinically. All intracranial aneurysms had a pronounced increase in wall permeability compared with the paired healthy MCA (P < .001). Regression analysis demonstrated a significant trend toward an increased K(trans) with increasing aneurysm size (P < .001). Logistic regression showed that K(trans) also predicted risk in anatomic (P = .02) and combined anatomic/clinical (P = .03) groups independent of size. We report the first evidence of dynamic contrast-enhanced MR imaging-modeled contrast permeability in intracranial aneurysms. We found that contrast agent permeability across the aneurysm wall correlated significantly with both aneurysm size and size-independent anatomic risk factors. In addition, K(trans) was a significant and size-independent predictor of morphologically and clinically defined high-risk aneurysms. © 2015 by American Journal of Neuroradiology.
Coupled THM Modeling of Hydroshearing Stimulation in Tight Fractured Volcanic Rock
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rinaldi, A. P.; Rutqvist, J.; Sonnenthal, E. L.
Here, we use the TOUGH-FLAC simulator for coupled thermo–hydro-mechanical modeling of well stimulation for an Enhanced Geothermal System (EGS) project. We also analyze the potential for injection-induced fracturing and reactivation of natural fractures in a porous medium with associated permeability enhancement. Our analysis aims to understand how far the EGS reservoir may grow and how the hydroshearing process relates to system conditions. We analyze the enhanced reservoir, or hydrosheared zone, by studying the extent of the failure zone using an elasto-plastic model, and accounting for permeability changes as a function of the induced stresses. For both fully saturated and unsaturatedmore » medium cases, the results demonstrate how EGS reservoir growth depends on the initial fluid phase, and how the reservoir extent changes as a function of two critical parameters: (1) the coefficient of friction, and (2) the permeability-enhancement factor. Furthermore, while well stimulation is driven by pressure exceeding the hydroshearing threshold, the modeling also demonstrates how injection-induced cooling further extends the effects of stimulation.« less
Coupled THM Modeling of Hydroshearing Stimulation in Tight Fractured Volcanic Rock
Rinaldi, A. P.; Rutqvist, J.; Sonnenthal, E. L.; ...
2014-03-18
Here, we use the TOUGH-FLAC simulator for coupled thermo–hydro-mechanical modeling of well stimulation for an Enhanced Geothermal System (EGS) project. We also analyze the potential for injection-induced fracturing and reactivation of natural fractures in a porous medium with associated permeability enhancement. Our analysis aims to understand how far the EGS reservoir may grow and how the hydroshearing process relates to system conditions. We analyze the enhanced reservoir, or hydrosheared zone, by studying the extent of the failure zone using an elasto-plastic model, and accounting for permeability changes as a function of the induced stresses. For both fully saturated and unsaturatedmore » medium cases, the results demonstrate how EGS reservoir growth depends on the initial fluid phase, and how the reservoir extent changes as a function of two critical parameters: (1) the coefficient of friction, and (2) the permeability-enhancement factor. Furthermore, while well stimulation is driven by pressure exceeding the hydroshearing threshold, the modeling also demonstrates how injection-induced cooling further extends the effects of stimulation.« less
Rossi Espagnet, M C; Bangiyev, L; Haber, M; Block, K T; Babb, J; Ruggiero, V; Boada, F; Gonen, O; Fatterpekar, G M
2015-08-01
The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging. © 2015 by American Journal of Neuroradiology.
Rossi Espagnet, M.C.; Bangiyev, L.; Haber, M.; Block, K.T.; Babb, J.; Ruggiero, V.; Boada, F.; Gonen, O.; Fatterpekar, G.M.
2015-01-01
BACKGROUNDANDPURPOSE The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. MATERIALS AND METHODS A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. RESULTS Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. CONCLUSIONS This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging. PMID:25953760
Conducting a 3D Converted Shear Wave Project to Reduce Exploration Risk at Wister, CA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Matlick, Skip; Walsh, Patrick; Rhodes, Greg
2015-06-30
Ormat sited 2 full-size exploration wells based on 3D seismic interpretation of fractures, prior drilling results, and temperature anomaly. The wells indicated commercial temperatures (>300 F), but almost no permeability, despite one of the wells being drilled within 820 ft of an older exploration well with reported indications of permeability. Following completion of the second well in 2012, Ormat undertook a lengthy program to 1) evaluate the lack of observed permeability, 2) estimate the likelihood of finding permeability with additional drilling, and 3) estimate resource size based on an anticipated extent of permeability.
Seo, Jeong-Woong; Hwang, Kyu-Min; Lee, Sung-Hoon; Kim, Dong-Wook; Park, Eun-Seok
2017-06-11
The objectives of this study were to prepare cocrystal composed of adefovir dipivoxil (AD) and stearic acid (SA) and to investigate the enhanced properties of the cocrystal. The cocrystal was prepared by antisolvent precipitation and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). The enhanced properties were evaluated by dissolution testing, permeability studies, and powder rheology analysis. The AD raw material has a cuboid-like crystal and the cocrystal has a needle shape. In the FT-IR study, there were bathochromic shifts caused by the hydrogen bonding. The melting point of the cocrystal was 52.9 °C, which was lower than that of AD. The XRPD pattern also had distinct differences, supporting the formation of a new crystalline form. The cocrystal showed changes in the lattice energy and the solvation strength, which caused an enhanced dissolution. The permeability was increased due to the SA, which acts as a P-gp inhibitor. The tabletability was enhanced due to the altered crystal habit. In conclusion, cocrystal containing AD and SA was successfully prepared, presenting advantages such as enhanced solubility, tabletability, and permeability. The use of the cocrystal is a desirable approach for the improved physicochemical properties.
Electrokinetic Enhanced Permanganate Delivery for Low Permeability Soil Remediation
NASA Astrophysics Data System (ADS)
Chowdhury, A. I.; Gerhard, J.; Reynolds, D. A.; Sleep, B. E.; O'Carroll, D. M.
2016-12-01
Contaminant mass sequestered in low permeability zones (LPZ) in the subsurface has become a significant concern due to back diffusion of contaminants, leading to contaminant rebound following treatment of the high permeability strata. In-situ remediation technologies such as in-situ chemical oxidation (ISCO) are promising, however, successful delivery of oxidants into silts and clays remains a challenge. Electrokinetics (EK) has been proposed as a technique that can overcome this challenge by delivering oxidants into low permeability soils. This study demonstrates the ability of EK to facilitate permanganate delivery into silt for treatment of trichloroethene (TCE). A two-dimensional sandbox was packed with alternate vertical layers of coarse sand and silt contaminated with high concentrations of aqueous phase TCE. Nine experiments were conducted to compare EK-enhanced in-situ chemical oxidation (EK-ISCO) to ISCO alone or EK alone. Frequent groundwater sampling at multiple locations combined with image analysis provided detailed mapping of TCE, permanganate, and manganese dioxide mass distributions. EK-ISCO successfully delivered the permanganate throughout the silt cross-section while ISCO without EK resulted in permanganate delivery only to the edges of the silt layer. EK-ISCO resulted in a 4.4 order-of-magnitude (OoM) reduction in TCE concentrations in the coarse sand compared to a 3.5 OoM reduction for ISCO alone. This study suggests that electrokinetics coupled with ISCO can achieve enhanced remediation of lower permeability strata, where remediation technologies for successful contaminant mass removal would otherwise be limited.
Permeable pavement surfaces are infiltration based stormwater control measures (SCM) commonly applied in parking lots to decrease impervious area and reduce runoff volume. Many are not optimally designed however, as little attention is given to draining a large enough contributin...
NASA Astrophysics Data System (ADS)
Reitan, Nina Kristine; Thuen, Marte; Goa, Pa˚L. Erik; de Lange Davies, Catharina
2010-05-01
Solid tumors are characterized by abnormal blood vessel organization, structure, and function. These abnormalities give rise to enhanced vascular permeability and may predict therapeutic responses. The permeability and architecture of the microvasculature in human osteosarcoma tumors growing in dorsal window chambers in athymic mice were measured by confocal laser scanning microscopy (CLSM) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Dextran (40 kDa) and Gadomer were used as molecular tracers for CLSM and DCE-MRI, respectively. A significant correlation was found between permeability indicators. The extravasation rate Ki as measured by CLSM correlated positively with DCE-MRI parameters, such as the volume transfer constant Ktrans and the initial slope of the contrast agent concentration-time curve. This demonstrates that these two techniques give complementary information. Extravasation was further related to microvascular structure and was found to correlate with the fractal dimension and vascular density. The structural parameter values that were obtained from CLSM images were higher for abnormal tumor vasculature than for normal vessels.
NASA Astrophysics Data System (ADS)
Mukuhira, Yusuke; Moriya, Hirokazu; Ito, Takatoshi; Asanuma, Hiroshi; Häring, Markus
2017-04-01
Understanding the details of pressure migration during hydraulic stimulation is important for the design of an energy extraction system and reservoir management, as well as for the mitigation of hazardous-induced seismicity. Based on microseismic and regional stress information, we estimated the pore pressure increase required to generate shear slip on an existing fracture during stimulation. Spatiotemporal analysis of pore pressure migration revealed that lower pore pressure migrates farther and faster and that higher pore pressure migrates more slowly. These phenomena can be explained by the relationship between fracture permeability and stress state criticality. Subcritical fractures experience shear slip following smaller increases of pore pressure and promote migration of pore pressure because of their enhanced permeability. The difference in migration rates between lower and higher pore pressures suggests that the optimum wellhead pressure is the one that can stimulate relatively permeable fractures, selectively. Its selection optimizes economic benefits and minimizes seismic risk.
Xu, Ziqian; Zeng, Wen; Sun, Jiayu; Chen, Wei; Zhang, Ruzhi; Yang, Zunyuan; Yao, Zunwei; Wang, Lei; Song, Li; Chen, Yushu; Zhang, Yu; Wang, Chunhua; Gong, Li; Wu, Bing; Wang, Tinghua; Zheng, Jie; Gao, Fabao
2017-09-01
Microvascular lesions of the body are one of the most serious complications that can affect patients with type 2 diabetes mellitus. The blood-brain barrier (BBB) is a highly selective permeable barrier around the microvessels of the brain. This study investigated BBB disruption in diabetic rhesus monkeys using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Multi-slice DCE-MRI was used to quantify BBB permeability. Five diabetic monkeys and six control monkeys underwent magnetic resonance brain imaging in 3 Tesla MRI system. Regions of the frontal cortex, the temporal cortex, the basal ganglia, the thalamus, and the hippocampus in the two groups were selected as regions of interest to calculate the value of the transport coefficient K trans using the extended Tofts model. Permeability in the diabetic monkeys was significantly increased as compared with permeability in the normal control monkeys. Histopathologically, zonula occludens protein-1 decreased, immunoglobulin G leaked out of the blood, and nuclear factor E2-related factor translocated from the cytoplasm to the nuclei. It is likely that diabetes contributed to the increased BBB permeability. Copyright © 2016 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Gamage, K.; Screaton, E.
2006-04-01
Elevated fluid pore pressures play a critical role in the development of accretionary complexes, including the development of the décollement zone. In this study, we used measured permeabilities of core samples from Ocean Drilling Program (ODP) Leg 190 to develop a permeability-porosity relationship for hemipelagic sediments at the toe of the Nankai accretionary complex. This permeability-porosity relationship was used in a one-dimensional loading and fluid flow model to simulate excess pore pressures and porosities. Simulated excess pore pressure ratios (as a fraction of lithostatic pressure-hydrostatic pressure) using the best fit permeability-porosity relationship were lower than predicted from previous studies. We then tested sensitivity of excess pore pressure ratios in the underthrust sediments to bulk permeability, lateral stress in the prism, and a hypothetical low-permeability barrier at the décollement. Our results demonstrated significant increase in pore pressures below the décollement with lower bulk permeability, such as obtained by using the lower boundary of permeability-porosity data, or when a low-permeability barrier is added at the décollement. In contrast, pore pressures in the underthrust sediments demonstrated less sensitivity to added lateral stresses in the prism, although the profile of the excess pore pressure ratio is affected. Both simulations with lateral stress and a low-permeability barrier at the décollement resulted in sharp increases in porosity at the décollement, similar to that observed in measured porosities. Furthermore, in both scenarios, maximum excess pore pressure ratios were found at the décollement, suggesting that either of these factors would contribute to stable sliding along the décollement.
Xiao, Meng; Zhang, Zhong-Zhi; Wang, Jing-Xiu; Zhang, Guang-Qing; Luo, Yi-Jing; Song, Zhao-Zheng; Zhang, Ji-Yuan
2013-11-01
The diversity of indigenous bacterial community and the functional species in the water samples from three production wells of a low permeability oil reservoir was investigated by high-throughput sequencing technology. The potential of application of indigenous bacteria for enhancing oil recovery was evaluated by examination of the effect of bacterial stimulation on the formation water-oil-rock surface interactions and micromodel test. The results showed that production well 88-122 had the most diverse bacterial community and functional species. The broth of indigenous bacteria stimulated by an organic nutrient activator at aerobic condition changed the wettability of the rock surface from oil-wet to water-wet. Micromodel test results showed that flooding using stimulated indigenous bacteria following water flooding improved oil recovery by 6.9% and 7.7% in fractured and unfractured micromodels, respectively. Therefore, the zone of low permeability reservoir has a great potential for indigenous microbial enhanced oil recovery. Copyright © 2013 Elsevier Ltd. All rights reserved.
Experimental Study on Oil Displacement Mechanism
NASA Astrophysics Data System (ADS)
Pi, Yanfu; Shao, Hongzhi; Pi, Yanming; Liu, Li
2018-02-01
In this work, the objective is enhancing oil recovery in offshore heavy oil after polymer flooding. The heterogeneous physical model is especially designed for oil fields with heavy oil. The comparative study of the two displacement experiments was carried out, and the experimental data was compared and analysed. The comparison between scheme one and scheme two was analysed from the production curve. The patterns of cores are analysed and compared with each other. It was found that the oil in the high permeability layer and medium permeability layer had been widely removed in the stage of binary combination flooding. There was a high degree of use in the low permeability layer. The recovery ratio is 66.29%. After polymer flooding, the addition of binary combination flooding in the heavy oil reservoir can greatly enhance oil recovery.
The Permeability Enhancing Mechanism of DMSO in Ceramide Bilayers Simulated by Molecular Dynamics
Notman, Rebecca; den Otter, Wouter K.; Noro, Massimo G.; Briels, W. J.; Anwar, Jamshed
2007-01-01
The lipids of the topmost layer of the skin, the stratum corneum, represent the primary barrier to molecules penetrating the skin. One approach to overcoming this barrier for the purpose of delivery of active molecules into or via the skin is to employ chemical permeability enhancers, such as dimethylsulfoxide (DMSO). How these molecules exert their effect at the molecular level is not understood. We have investigated the interaction of DMSO with gel-phase bilayers of ceramide 2, the predominant lipid in the stratum corneum, by means of molecular dynamics simulations. The simulations satisfactorily reproduce the phase behavior and the known structural parameters of ceramide 2 bilayers in water. The effect of DMSO on the gel-phase bilayers was investigated at various concentrations over the range 0.0−0.6 mol fraction DMSO. The DMSO molecules accumulate in the headgroup region and weaken the lateral forces between the ceramides. At high concentrations of DMSO (≥0.4 mol fraction), the ceramide bilayers undergo a phase transition from the gel phase to the liquid crystalline phase. The liquid-crystalline phase of ceramides is expected to be markedly more permeable to solutes than the gel phase. The results are consistent with the experimental evidence that high concentrations of DMSO fluidize the stratum corneum lipids and enhance permeability. PMID:17513383
DOE Office of Scientific and Technical Information (OSTI.GOV)
Balgley, Renata; de Ruiter, Graham; Evmenenko, Guennadi
In this paper, we demonstrate how photochemically enhancing the permeability of metal–organic assemblies results in a significant enhancement of the electrochemical activity of metal complexes located within the assembly. The molecular assemblies consist of different layers of redox-active metal complexes ([M(mbpy-py)3][PF6]2; M = Ru or Os) that are separated by redox-inactive spacers consisting of 1,4-bis[2-(4-pyridyl)ethenyl]benzene (BPEB) and PdCl2 of variable thicknesses (0–13.4 nm). UV-irradiation (λ = 254 nm) of our assemblies induces a photochemical reaction in the redox-inactive spacer increasing the permeability of the assembly. The observed increase was evident by trapping organic (nBu4NBF4) and inorganic (NiCl2) salts inside themore » assemblies, and by evaluating the electrochemical response of quinones absorbed inside the molecular assemblies before and after UV irradiation. The increase in permeability is reflected by higher currents and a change in the directionality of electron transfer, i.e., from mono- to bidirectional, between the redox-active metal complexes and the electrode surface. The supramolecular structure of the assemblies dominates the overall electron transfer properties and overrules possible electron transfer mediated by the extensive π-conjugation of its individual organic components.« less
NASA Astrophysics Data System (ADS)
Jeanne, Pierre; Rutqvist, Jonny; Rinaldi, Antonio Pio; Dobson, Patrick F.; Walters, Mark; Hartline, Craig; Garcia, Julio
2015-11-01
In this paper, we use the Seismicity-Based Reservoir Characterization approach to study the spatiotemporal dynamics of an injection-induced microseismic cloud, monitored during the stimulation of an enhanced geothermal system, and associated with the Northwest Geysers Enhanced Geothermal System (EGS) Demonstration project (California). We identified the development of a seismically quiet domain around the injection well surrounded by a seismically active domain. Then we compare these observations with the results of 3-D Thermo-Hydro-Mechanical simulations of the EGS, which accounts for changes in permeability as a function of the effective normal stress and the plastic strain. The results of our modeling show that (1) the aseismic domain is caused by both the presence of the injected cold water and by thermal processes. These thermal processes cause a cooling-stress reduction, which prevent shear reactivation and favors fracture opening by reducing effective normal stress and locally increasing the permeability. This process is accompanied by aseismic plastic shear strain. (2) In the seismic domain, microseismicity is caused by the reactivation of the preexisting fractures, resulting from an increase in injection-induced pore pressure. Our modeling indicates that in this domain, permeability evolves according to the effective normal stress acting on the shear zones, whereas shearing of preexisting fractures may have a low impact on permeability. We attribute this lack of permeability gain to the fact that the initial permeabilities of these preexisting fractures are already high (up to 2 orders of magnitude higher than the host rock) and may already be fully dilated by past tectonic straining.
The influence of interfacial slip on two-phase flow in rough pores
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kucala, Alec; Martinez, Mario J.; Wang, Yifeng
The migration and trapping of supercritical CO 2 (scCO 2) in geologic carbon storage is strongly dependent on the geometry and wettability of the pore network in the reservoir rock. During displacement, resident fluids may become trapped in the pits of a rough pore surface forming an immiscible two-phase fluid interface with the invading fluid, allowing apparent slip flow at this interface. We present a two-phase fluid dynamics model, including interfacial tension, to characterize the impact of mineral surface roughness on this slip flow. We show that the slip flow can be cast in more familiar terms as a contact-anglemore » (wettability)-dependent effective permeability to the invading fluid, a nondimensional measurement which relates the interfacial slip to the pore geometry. The analysis shows the surface roughness-induced slip flow can effectively increase or decrease this effective permeability, depending on the wettability and roughness of the mineral surfaces. Configurations of the pore geometry where interfacial slip has a tangible influence on permeability have been identified. The results suggest that for large roughness features, permeability to CO 2 may be enhanced by approximately 30% during drainage, while the permeability to brine during reimbibition may be enhanced or diminished by 60%, depending on the contact angle with the mineral surfaces and degrees of roughness. For smaller roughness features, the changes in permeability through interfacial slip are small. As a result, a much larger range of effective permeabilities are suggested for general fluid pairs and contact angles, including occlusion of the pore by the trapped phase.« less
NASA Astrophysics Data System (ADS)
Zhang, Yanhua; Clennell, Michael B.; Delle Piane, Claudio; Ahmed, Shakil; Sarout, Joel
2016-12-01
This generic 2D elastic-plastic modelling investigated the reactivation of a small isolated and critically-stressed fault in carbonate rocks at a reservoir depth level for fluid depletion and normal-faulting stress conditions. The model properties and boundary conditions are based on field and laboratory experimental data from a carbonate reservoir. The results show that a pore pressure perturbation of -25 MPa by depletion can lead to the reactivation of the fault and parts of the surrounding damage zones, producing normal-faulting downthrows and strain localization. The mechanism triggering fault reactivation in a carbonate field is the increase of shear stresses with pore-pressure reduction, due to the decrease of the absolute horizontal stress, which leads to an expanded Mohr's circle and mechanical failure, consistent with the predictions of previous poroelastic models. Two scenarios for fault and damage-zone permeability development are explored: (1) large permeability enhancement of a sealing fault upon reactivation, and (2) fault and damage zone permeability development governed by effective mean stress. In the first scenario, the fault becomes highly permeable to across- and along-fault fluid transport, removing local pore pressure highs/lows arising from the presence of the initially sealing fault. In the second scenario, reactivation induces small permeability enhancement in the fault and parts of damage zones, followed by small post-reactivation permeability reduction. Such permeability changes do not appear to change the original flow capacity of the fault or modify the fluid flow velocity fields dramatically.
The influence of interfacial slip on two-phase flow in rough pores
Kucala, Alec; Martinez, Mario J.; Wang, Yifeng; ...
2017-08-01
The migration and trapping of supercritical CO 2 (scCO 2) in geologic carbon storage is strongly dependent on the geometry and wettability of the pore network in the reservoir rock. During displacement, resident fluids may become trapped in the pits of a rough pore surface forming an immiscible two-phase fluid interface with the invading fluid, allowing apparent slip flow at this interface. We present a two-phase fluid dynamics model, including interfacial tension, to characterize the impact of mineral surface roughness on this slip flow. We show that the slip flow can be cast in more familiar terms as a contact-anglemore » (wettability)-dependent effective permeability to the invading fluid, a nondimensional measurement which relates the interfacial slip to the pore geometry. The analysis shows the surface roughness-induced slip flow can effectively increase or decrease this effective permeability, depending on the wettability and roughness of the mineral surfaces. Configurations of the pore geometry where interfacial slip has a tangible influence on permeability have been identified. The results suggest that for large roughness features, permeability to CO 2 may be enhanced by approximately 30% during drainage, while the permeability to brine during reimbibition may be enhanced or diminished by 60%, depending on the contact angle with the mineral surfaces and degrees of roughness. For smaller roughness features, the changes in permeability through interfacial slip are small. As a result, a much larger range of effective permeabilities are suggested for general fluid pairs and contact angles, including occlusion of the pore by the trapped phase.« less
The influence of interfacial slip on two-phase flow in rough pores
NASA Astrophysics Data System (ADS)
Kucala, Alec; Martinez, Mario J.; Wang, Yifeng; Noble, David R.
2017-08-01
The migration and trapping of supercritical CO2 (scCO2) in geologic carbon storage is strongly dependent on the geometry and wettability of the pore network in the reservoir rock. During displacement, resident fluids may become trapped in the pits of a rough pore surface forming an immiscible two-phase fluid interface with the invading fluid, allowing apparent slip flow at this interface. We present a two-phase fluid dynamics model, including interfacial tension, to characterize the impact of mineral surface roughness on this slip flow. We show that the slip flow can be cast in more familiar terms as a contact-angle (wettability)-dependent effective permeability to the invading fluid, a nondimensional measurement which relates the interfacial slip to the pore geometry. The analysis shows the surface roughness-induced slip flow can effectively increase or decrease this effective permeability, depending on the wettability and roughness of the mineral surfaces. Configurations of the pore geometry where interfacial slip has a tangible influence on permeability have been identified. The results suggest that for large roughness features, permeability to CO2 may be enhanced by approximately 30% during drainage, while the permeability to brine during reimbibition may be enhanced or diminished by 60%, depending on the contact angle with the mineral surfaces and degrees of roughness. For smaller roughness features, the changes in permeability through interfacial slip are small. A much larger range of effective permeabilities are suggested for general fluid pairs and contact angles, including occlusion of the pore by the trapped phase.
An analytical model for inductively coupled implantable biomedical devices with ferrite rods.
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.
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.
Birukova, Anna A; Arce, Fernando T; Moldobaeva, Nurgul; Dudek, Steven M; Garcia, Joe G N; Lal, Ratnesh; Birukov, Konstantin G
2009-03-01
Actomyosin contraction directly regulates endothelial cell (EC) permeability, but intracellular redistribution of cytoskeletal tension associated with EC permeability is poorly understood. We used atomic force microscopy (AFM), EC permeability assays, and fluorescence microscopy to link barrier regulation, cell remodeling, and cytoskeletal mechanical properties in EC treated with barrier-protective as well as barrier-disruptive agonists. Thrombin, vascular endothelial growth factor, and hydrogen peroxide increased EC permeability, disrupted cell junctions, and induced stress fiber formation. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, hepatocyte growth factor, and iloprost tightened EC barriers, enhanced peripheral actin cytoskeleton and adherens junctions, and abolished thrombin-induced permeability and EC remodeling. AFM force mapping and imaging showed differential distribution of cell stiffness: barrier-disruptive agonists increased stiffness in the central region, and barrier-protective agents decreased stiffness in the center and increased it at the periphery. Attenuation of thrombin-induced permeability correlates well with stiffness changes from the cell center to periphery. These results directly link for the first time the patterns of cell stiffness with specific EC permeability responses.
Heade, Joanne; Maher, Sam; Bleiel, Sinead B; Brayden, David J
2018-06-01
In addition to their solubilizing properties, excipients used in lipid-based formulations can improve intestinal permeability of macromolecules. We determined whether admixing of medium-chain fatty acid (MCFA) permeation enhancers with a lipoidal excipient (Labrasol ® ) could potentiate transepithelial flux of a poorly permeable macromolecule (fluorescein isothiocyanate dextran 4 kDa [FD4]) across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of sodium caprate (C 10 ), sodium undecylenate (C 11:1 ), or sodium laurate (C 12 ) combined with Labrasol ® increased the apparent permeability coefficient (P app ) of FD4 to values typically seen with higher concentrations of MCFAs or Labrasol ® alone. For example, combination of C 11:1 (0.5 mg/mL) with Labrasol ® (1 mg/mL) increased the P app of FD4 by 10- and 11-fold over the respective individual agents at the same concentrations where no enhancement was evident. The increased enhancement ratios seen with the combinations were associated with some perturbation in intestinal histology and with attenuation of an epithelial functional measure, carbachol-stimulated inward short-circuit current. In conclusion, combining three MCFAs separately with Labrasol ® increased the P app of FD4 to values greater than those seen for MCFAs or Labrasol ® alone. Ultimately, this may permit lower concentrations of MCFA to be used in combination with other excipients in oral formulations of poorly permeable molecules. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Cui, Kai; Sun, Shanshan; Xiao, Meng; Liu, Tongjing; Xu, Quanshu; Dong, Honghong; Wang, Di; Gong, Yejing; Sha, Te; Hou, Jirui; Zhang, Zhongzhi; Fu, Pengcheng
2018-05-11
Microbial mineral illization has been investigated for its role in the extraction and recovery of metals from ores. Here we report our application of mineral bioillization for the microbial enhanced oil recovery in low-permeability oil reservoirs. It aimed to reveal the etching mechanism of the four Fe (III)-reducing microbial strains under anaerobic growth conditions on the Ca-montmorillonite. The mineralogical characterization of the Ca-montmorillonite was performed by Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electron microscopy and energy dispersive spectrometer. Results showed that the microbial strains could efficiently reduce Fe (III) at an optimal rate of 71 %, and alter the crystal lattice structure of the lamella to promote the interlayer cation exchange, and to efficiently inhibit the Ca-montmorillonite swelling at an inhibitory rate of 48.9 %. Importance Microbial mineral illization is ubiquitous in the natural environment. Microbes in low-permeability reservoirs are able to enable the alteration of the structure and phase of the Fe-poor minerals by reducing Fe (III) and inhibiting clay swelling which is still poorly studied. This study aimed to reveal the interaction mechanism between Fe (III)-reducing bacterial strains and Ca-montmorillonite under anaerobic atmosphere, and to investigate the extent and rates of Fe (III) reduction and phase changes with their activities. Application of Fe (III)-reducing bacteria will provide a new way to inhibit clay swelling, to elevate reservoir permeability, and to reduce pore throat resistance after water flooding for enhanced oil recovery in low-permeability reservoirs. Copyright © 2018 American Society for Microbiology.
Data report: Permeabilities of eastern equatorial Pacific and Peru margin sediments
Gamage, Kusali; Bekins, Barbara A.; Screaton, Elizabeth; Jørgensen, Bo B.; D'Hondt, Steven L.; Miller, D. Jay
2006-01-01
Constant-flow permeability tests were conducted on core samples from Ocean Drilling Program Leg 201 from the eastern equatorial Pacific and the Peru margin. Eighteen whole-round core samples from Sites 1225, 1226, 1227, 1230, and 1231 were tested for vertical permeabilities. Sites 1225, 1226, and 1231 represent sediments of the open ocean, whereas Sites 1227 and 1230 represent sediments of the ocean margin. Measured vertical permeabilities vary from ~8 x 10–19 m2 to ~1 x 10–16 m2 for a porosity range of 45%–90%.
2017 GTO Project review Laboratory Evaluation of EGS Shear Stimulation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bauer, Stephen J.
The objectives and purpose of this research has been to produce laboratory-based experimental and numerical analyses to provide a physics-based understanding of shear stimulation phenomena (hydroshearing) and its evolution during stimulation. Water was flowed along fractures in hot and stressed fractured rock, to promote slip. The controlled laboratory experiments provide a high resolution/high quality data resource for evaluation of analysis methods developed by DOE to assess EGS “behavior” during this stimulation process. Segments of the experimental program will provide data sets for model input parameters, i.e., material properties, and other segments of the experimental program will represent small scale physicalmore » models of an EGS system, which may be modeled. The coupled lab/analysis project has been a study of the response of a fracture in hot, water-saturated fractured rock to shear stress experiencing fluid flow. Under this condition, the fracture experiences a combination of potential pore pressure changes and fracture surface cooling, resulting in slip along the fracture. The laboratory work provides a means to assess the role of “hydroshearing” on permeability enhancement in reservoir stimulation. Using the laboratory experiments and results to define boundary and input/output conditions of pore pressure, thermal stress, fracture shear deformation and fluid flow, and models were developed and simulations completed by the University of Oklahoma team. The analysis methods are ones used on field scale problems. The sophisticated numerical models developed contain parameters present in the field. The analysis results provide insight into the role of fracture slip on permeability enhancement-“hydroshear” is to be obtained. The work will provide valuable input data to evaluate stimulation models, thus helping design effective EGS.« less
Thermal treatment of low permeability soils using electrical resistance heating
DOE Office of Scientific and Technical Information (OSTI.GOV)
Udell, K.S.
1996-08-01
The acceleration of recovery rates of second phase liquid contaminants from the subsurface during gas or water pumping operations is realized by increasing the soil and ground water temperature. Electrical heating with AC current is one method of increasing the soil and groundwater temperature and has particular applicability to low permeability soils. Several mechanisms have been identified that account for the enhanced removal of the contaminants during electrical heating. These are vaporization of liquid contaminants with low boiling points, temperature-enhanced evaporation rates of semi-volatile components, and removal of residual contaminants by the boiling of residual water. Field scale studies ofmore » electrical heating and fluid extraction show the effectiveness of this technique and its applicability to contaminants found both above and below the water table and within low permeability soils. 10 refs., 8 figs.« less
ERIC Educational Resources Information Center
Floris, S.; Blezer, E. L. A.; Schreibelt, G.; Dopp, E.; van der Pol, S. M. A.; Schadee-Eestermans, I. L.; Nicolay, K.; Dijkstra, C. D.; de Vries, H. E.
2004-01-01
Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive…
USDA-ARS?s Scientific Manuscript database
Gas-permeable membranes coupled with low-rate aeration are useful to recover ammonium from livestock effluents. In this study, the role of inorganic carbon (bicarbonate) to enhance the nitrogen (N) recovery process was evaluated using synthetic effluents with various ammonium to bicarbonate molar ra...
NASA Technical Reports Server (NTRS)
Nettles, A. T.
1995-01-01
Hercules IM7/8552 carbon/epoxy and Hysol EA 9394 epoxy adhesive bonded between composite/titanium were tested for permeability after various numbers of thermal cycles between 100 C and liquid nitrogen (-196 C). The specimens were quenched from the 100 C temperature into liquid nitrogen to induce thermal shock into the material. Results showed that the carbon/epoxy system was practically impermeable even after 12 thermal cycles. The EA 9394 adhesive bondline was more permeable than the carbon/epoxy, but vacuum mixing minimized the permeability and kept it within allowable limits. Thermal cycling had little effect on the permeability values of the bondline specimens.
A probabilistic damage model of stress-induced permeability anisotropy during cataclastic flow
NASA Astrophysics Data System (ADS)
Zhu, Wenlu; MontéSi, Laurent G. J.; Wong, Teng-Fong
2007-10-01
A fundamental understanding of the effect of stress on permeability evolution is important for many fault mechanics and reservoir engineering problems. Recent laboratory measurements demonstrate that in the cataclastic flow regime, the stress-induced anisotropic reduction of permeability in porous rocks can be separated into 3 different stages. In the elastic regime (stage I), permeability and porosity reduction are solely controlled by the effective mean stress, with negligible permeability anisotropy. Stage II starts at the onset of shear-enhanced compaction, when a critical yield stress is attained. In stage II, the deviatoric stress exerts primary control over permeability and porosity evolution. The increase in deviatoric stress results in drastic permeability and porosity reduction and considerable permeability anisotropy. The transition from stage II to stage III takes place progressively during the development of pervasive cataclastic flow. In stage III, permeability and porosity reduction becomes gradual again, and permeability anisotropy diminishes. Microstructural observations on deformed samples using laser confocal microscopy reveal that stress-induced microcracking and pore collapse are the primary forms of damage during cataclastic flow. A probabilistic damage model is formulated to characterize the effects of stress on permeability and its anisotropy. In our model, the effects of both effective mean stress and differential stress on permeability evolution are calculated. By introducing stress sensitivity coefficients, we propose a first-order description of the dependence of permeability evolution on different loading paths. Built upon the micromechanisms of deformation in porous rocks, this unified model provides new insight into the coupling of stress and permeability.
Permeability evolution during non-linear viscous creep of porous calcite rocks
NASA Astrophysics Data System (ADS)
Xiao, X.; Evans, B.; Bernabe, Y.
2005-12-01
Below the brittle-ductile transition, permeability might be exceedingly small, due to compaction facilitated by intracrystalline plasticity or viscous creep. The ductile lower crust may consist of depth intervals or isolated domains of relatively high permeability, where the fluid pressures are at or near lithostatic values. Fluid escape from metamorphic rocks likely involves episodic hydrofracturing or porosity-wave propagation driven by the difference between the gradients of fluid and rock pressure. Although it is generally agreed that fluid flow in ductile porous rocks is critically dependent on the interplay between the fluid properties and the rheology of the rock matrix, more experimental work is needed to elucidate the ways that permeability and porosity change during deformation at elevated temperature and pressures. Triaxial tests of synthetic calcite marbles containing 10, 20, or 30 wt% quartz and up to 9% residual porosity done at temperature up to 873K, reported earlier (Xiao and Evans, 2003), indicate that shear-enhanced compaction occurs under triaxial conditions, roughly consistent with a model of void collapse by viscous creep (Budiansky et al., 1982). In this study, we report the effect of viscous creep on the permeability of those porous rocks during both isostatic and conventional triaxial loading. The tests were performed at confining pressure of 300 MPa, pore pressures between 50 to 290 MPa, temperatures from 673 to 873K and strain rates of 3.0× 10-5 s-1. Argon gas was used as the pore fluid. Under isostatic loading conditions, permeability, k, is nonlinearly related to porosity, Φ. Over small changes in porosity, the two parameters are approximately related as k~Φn. The exponent n progressively increases as the porosity decreases to a finite value, suggesting a percolation porosity. When subjected to triaxial deformation, the calcite-quartz aggregates exhibit a shear-enhanced compaction, but permeability does not decrease as rapidly as it does during isostatic conditions; the exponent n varies between 2 and 3. Non-isostatic deformation seems to reduce the percolation threshold, and, in fact, enhances the permeability relative to that at the same porosity during isostatic compaction. Our data provide constraints on the governing parameters of the compaction theory, and may have far-reaching implications for melt extraction from partially molten rocks, for the expulsion of sedimentary fluids, and for fluid flow during deformation and metamorphism.
Seismically active volume not a good indicator of the stimulated reservoir: evidence from Paralana
NASA Astrophysics Data System (ADS)
Riffault, J.; Dempsey, D. E.; Karra, S.; Archer, R.
2017-12-01
Hydraulic stimulation is routinely carried out in EGS projects in order to engineer the geothermal reservoir, triggering large amounts of seismicity. There is broad consensus that hydroshearing, the shear failure of existing fractures caused by pore pressure increasing above a critical value, is the mechanism primarily responsible for the seismicity. It is also often assumed to be the primary mechanism behind permeability enhancement and thus reservoir creation, although several other physical processes, such as thermal and chemical effects, and tensile failure, can also contribute. An extension of this assumption is that the seismically active volume reflects the extent of the stimulated reservoir. This may not always be the case. Hydraulic stimulation aims to improve injectivity, which we define as the ratio of injection rate to wellhead pressure. During the Paralana-2 EGS stimulation, undertaken in South Australia in 2011, injectivity increased linearly over time, implying permeability enhancement. Concurrently, 4754 micro-earthquakes were detected and located. We have spatially averaged hypocentre positions in order to image the spatio-temporally evolving seismicity cloud and its main features. Using an established correlation from a previous EGS experiment, we use hypocentre density as a proxy measure of pore pressure increase. Knowing then how pressure and injectivity evolve over time, we develop an inversion procedure based on reservoir simulation to infer how permeability has evolved around the well. Our results indicate that, although there is significant permeability enhancement close to the wellbore, this is largely uncoupled from the seismically active volume that extends much further away. In other words, for the Paralana stimulation, the seismicity cloud is a poor indicator of the stimulated reservoir volume. It further implies that hydroshearing itself is not the main cause of permeability enhancement at Paralana. Our study suggests that past stimulations may need to be revisited and a stronger case made for estimates of the stimulated reservoir.
Dempsey, David; Kelkar, Sharad; Davatzes, Nick; Hickman, Stephen H.; Moos, Daniel
2015-01-01
Creation of an Enhanced Geothermal System relies on stimulation of fracture permeability through self-propping shear failure that creates a complex fracture network with high surface area for efficient heat transfer. In 2010, shear stimulation was carried out in well 27-15 at Desert Peak geothermal field, Nevada, by injecting cold water at pressure less than the minimum principal stress. An order-of-magnitude improvement in well injectivity was recorded. Here, we describe a numerical model that accounts for injection-induced stress changes and permeability enhancement during this stimulation. In a two-part study, we use the coupled thermo-hydrological-mechanical simulator FEHM to: (i) construct a wellbore model for non-steady bottom-hole temperature and pressure conditions during the injection, and (ii) apply these pressures and temperatures as a source term in a numerical model of the stimulation. In this model, a Mohr-Coulomb failure criterion and empirical fracture permeability is developed to describe permeability evolution of the fractured rock. The numerical model is calibrated using laboratory measurements of material properties on representative core samples and wellhead records of injection pressure and mass flow during the shear stimulation. The model captures both the absence of stimulation at low wellhead pressure (WHP ≤1.7 and ≤2.4 MPa) as well as the timing and magnitude of injectivity rise at medium WHP (3.1 MPa). Results indicate that thermoelastic effects near the wellbore and the associated non-local stresses further from the well combine to propagate a failure front away from the injection well. Elevated WHP promotes failure, increases the injection rate, and cools the wellbore; however, as the overpressure drops off with distance, thermal and non-local stresses play an ongoing role in promoting shear failure at increasing distance from the well.
Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H; Van Gordon, Samuel B; Smith, Nataliya; North, Justin C; McElhaney, Rayburt; Aston, Christopher E; Shobeiri, S Abbas; Kropp, Bradley P; Greenwood-Van Meerveld, Beverley; Hurst, Robert E
2016-03-01
Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Effects of temperature on the development of low permeability in concretes.
DOT National Transportation Integrated Search
1998-02-01
This study evaluated the effects of temperature on the strength and permeability of concretes containing pozzolans (fly ash and silica fume) and slag. Two test programs were conducted. In the first, one control and five experimental mixtures containi...
NASA Astrophysics Data System (ADS)
Marble, J.; Carroll, K. C.; Brusseau, M. L.; Plaschke, M.; Brinker, F.
2013-12-01
Source zones located in relatively deep, low-permeability formations provide special challenges for remediation. Application of permeable reactive barriers, in-situ thermal, or electrokinetic methods would be expensive and generally impractical. In addition, the use of enhanced mass-removal approaches based on reagent injection (e.g., ISCO, enhanced-solubility reagents) is likely to be ineffective. One possible approach for such conditions is to create a persistent treatment zone for purposes of containment. This study examines the efficacy of this approach for containment and treatment of contaminants in a lower permeability zone using potassium permanganate (KMnO4) as the reactant. A localized 1,1-dichloroethene (DCE) source zone is present in a section of the Tucson International Airport Area (TIAA) Superfund Site. Characterization studies identified the source of DCE to be located in lower-permeability strata adjacent to the water table. Bench-scale studies were conducted using core material collected from boreholes drilled at the site to measure DCE concentrations and determine natural oxidant demand. The reactive zone was created by injecting ~1.7% KMnO4 solution into multiple wells screened within the lower-permeability unit. The site has been monitored for ~8 years to characterize the spatial distribution of DCE and permanganate. KMnO4 continues to persist at the site, demonstrating successful creation of a long-term reactive zone. Additionally, the footprint of the DCE contaminant plume in groundwater has decreased continuously with time. This project illustrates the application of ISCO as a reactive-treatment system for lower-permeability source zones, which appears to effectively mitigate persistent mass flux into groundwater.
Jeanne, Pierre; Rutqvist, Jonny; Rinaldi, Antonio Pio; ...
2015-10-27
In this paper, we use the Seismicity-Based Reservoir Characterization approach to study the spatiotemporal dynamics of an injection-induced microseismic cloud, monitored during the stimulation of an enhanced geothermal system, and associated with the Northwest Geysers Enhanced Geothermal System (EGS) Demonstration project (California). We identified the development of a seismically quiet domain around the injection well surrounded by a seismically active domain. Then we compare these observations with the results of 3-D Thermo-Hydro-Mechanical simulations of the EGS, which accounts for changes in permeability as a function of the effective normal stress and the plastic strain. The results of our modeling showmore » that the aseismic domain is caused by both the presence of the injected cold water and by thermal processes. These thermal processes cause a cooling-stress reduction, which prevent shear reactivation and favors fracture opening by reducing effective normal stress and locally increasing the permeability. This process is accompanied by aseismic plastic shear strain. In the seismic domain, microseismicity is caused by the reactivation of the preexisting fractures, resulting from an increase in injection-induced pore pressure. Our modeling indicates that in this domain, permeability evolves according to the effective normal stress acting on the shear zones, whereas shearing of preexisting fractures may have a low impact on permeability. We attribute this lack of permeability gain to the fact that the initial permeabilities of these preexisting fractures are already high (up to 2 orders of magnitude higher than the host rock) and may already be fully dilated by past tectonic straining.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeanne, Pierre; Rutqvist, Jonny; Rinaldi, Antonio Pio
In this paper, we use the Seismicity-Based Reservoir Characterization approach to study the spatiotemporal dynamics of an injection-induced microseismic cloud, monitored during the stimulation of an enhanced geothermal system, and associated with the Northwest Geysers Enhanced Geothermal System (EGS) Demonstration project (California). We identified the development of a seismically quiet domain around the injection well surrounded by a seismically active domain. Then we compare these observations with the results of 3-D Thermo-Hydro-Mechanical simulations of the EGS, which accounts for changes in permeability as a function of the effective normal stress and the plastic strain. The results of our modeling showmore » that the aseismic domain is caused by both the presence of the injected cold water and by thermal processes. These thermal processes cause a cooling-stress reduction, which prevent shear reactivation and favors fracture opening by reducing effective normal stress and locally increasing the permeability. This process is accompanied by aseismic plastic shear strain. In the seismic domain, microseismicity is caused by the reactivation of the preexisting fractures, resulting from an increase in injection-induced pore pressure. Our modeling indicates that in this domain, permeability evolves according to the effective normal stress acting on the shear zones, whereas shearing of preexisting fractures may have a low impact on permeability. We attribute this lack of permeability gain to the fact that the initial permeabilities of these preexisting fractures are already high (up to 2 orders of magnitude higher than the host rock) and may already be fully dilated by past tectonic straining.« less
In vitro evaluation of dendrimer prodrugs for oral drug delivery.
Najlah, Mohammad; Freeman, Sally; Attwood, David; D'Emanuele, Antony
2007-05-04
Dendrimer-based prodrugs were used to enhance the transepithelial permeability of naproxen, a low solubility model drug. The stability of the dendrimer-naproxen link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM) dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity of conjugates towards Caco-2 cells was determined and the transport of the conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in 50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2 cells for 3h. Permeability studies showed a significant enhancement in the transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the highest permeability. Dendrimer-based prodrugs with appropriate linkers have potential as carriers for the oral delivery of low solubility drugs such as naproxen.
Zhao, Guoying; Duan, Jingze; Xie, Yan; Lin, Guobei; Luo, Huilin; Li, Guowen; Yuan, Xiurong
2013-07-01
The aim of this study was to investigate the effects of solid dispersions (SD) and self-emulsifying (SE) formulations on the solubility and absorption properties of active components in total flavones of Hippophae rhamnoides L. (TFH). The solubility, dissolution rate, permeability and pharmacokinetics of isorhamnetin, quercetin and kaempferol in TFH SD/SE formulations and TFH were compared. The results showed that the solubility and dissolution rate of isorhamnetin, quercetin and kaempferol in SD/SE formulations were significantly enhanced compared to those in TFH, however, their intestinal permeability was comparable. The bioavailability of isorhamnetin, quercetin and kaempferol in rats remarkably increased after oral administration of TFH SD formulations compared to TFH, but there was no significant increase after oral administration of TFH SE formulations. The results of this study indicated the SD formulations on the improvement of pharmacokinetic properties of isorhamnetin, quercetin and kaempferol in TFH were much better than those of SE formulations. The improvement of pharmacokinetic properties of isorhamnetin, quercetin and kaempferol in TFH by SD formulations was probably ascribed to the enhancement of the solubility and dissolution of the three components, but was not relevant to the intestinal permeability. Therefore, as for herb extracts containing multiple components, especially for their major components with poor water solubility, solid dispersion formulations might have the better potential to enhance their bioavailability.
Gajra, Balaram; Patel, Ravi R; Dalwadi, Chintan
2016-01-01
The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.
Improving permeability and oral absorption of mangiferin by phospholipid complexation.
Ma, Hequn; Chen, Hongming; Sun, Le; Tong, Lijin; Zhang, Tianhong
2014-03-01
Mangiferin is an active ingredient of medicinal plant with poor hydrophilicity and lipophilicity. Many reports focused on improving aqueous solubility, but oral bioavailability of mangiferin was still limited. In this study, we intended to increase not only solubility, but also membrane permeability of mangiferin by a phospholipid complexation technique. The new complex's physicochemical properties were characterized in terms of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), aqueous solubility, oil-water partition coefficient and in vitro dissolution. The intestinal absorption of the complex was studied by the rat in situ intestinal perfusion model. After oral administration of mangiferin-phospholipid complex and crude mangiferin in rats, the concentrations of mangiferin were determined by a validated RP-HPLC method. Results showed that the solubility of the complex in water and in n-octanol was enhanced and the oil-water partition coefficient was improved by 6.2 times and the intestinal permeability in rats was enhanced significantly. Peak plasma concentration and AUC of mangiferin from the complex (Cmax: 377.66 μg/L, AUC: 1039.94 μg/L*h) were higher than crude mangiferin (Cmax: 180 μg/L, AUC: 2355.63 μg/L*h). In view of improved solubility and enhanced permeability, phospholipid complexation technique can increase bioavailability of mangiferin by 2.3 times in comparison to the crude mangiferin. Copyright © 2013 Elsevier B.V. All rights reserved.
Tichet, Mélanie; Prod'Homme, Virginie; Fenouille, Nina; Ambrosetti, Damien; Mallavialle, Aude; Cerezo, Michael; Ohanna, Mickaël; Audebert, Stéphane; Rocchi, Stéphane; Giacchero, Damien; Boukari, Fériel; Allegra, Maryline; Chambard, Jean-Claude; Lacour, Jean-Philippe; Michiels, Jean-François; Borg, Jean-Paul; Deckert, Marcel; Tartare-Deckert, Sophie
2015-04-30
Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis.
Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R
2015-06-01
In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood-brain barrier breakdown. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Tsai, Meng-Tsan; Chang, Feng-Yu; Lee, Cheng-Kuang; Gong, Cihun-Siyong Alex; Lin, Yu-Xiang; Lee, Jiann-Der; Yang, Chih-Hsun; Liu, Hao-Li
2014-01-01
Focused ultrasound (FUS) can be used to locally and temporally enhance vascular permeability, improving the efficiency of drug delivery from the blood vessels into the surrounding tissue. However, it is difficult to evaluate in real time the effect induced by FUS and to noninvasively observe the permeability enhancement. In this study, speckle-variance optical coherence tomography (SVOCT) was implemented for the investigation of temporal effects on vessels induced by FUS treatment. With OCT scanning, the dynamic change in vessels during FUS exposure can be observed and studied. Moreover, the vascular effects induced by FUS treatment with and without the presence of microbubbles were investigated and quantitatively compared. Additionally, 2D and 3D speckle-variance images were used for quantitative observation of blood leakage from vessels due to the permeability enhancement caused by FUS, which could be an indicator that can be used to determine the influence of FUS power exposure. In conclusion, SVOCT can be a useful tool for monitoring FUS treatment in real time, facilitating the dynamic observation of temporal effects and helping to determine the optimal FUS power. PMID:25071945
Bioinspired Tuning of Hydrogel Permeability-Rigidity Dependency for 3D Cell Culture
NASA Astrophysics Data System (ADS)
Lee, Min Kyung; Rich, Max H.; Baek, Kwanghyun; Lee, Jonghwi; Kong, Hyunjoon
2015-03-01
Hydrogels are being extensively used for three-dimensional immobilization and culture of cells in fundamental biological studies, biochemical processes, and clinical treatments. However, it is still a challenge to support viability and regulate phenotypic activities of cells in a structurally stable gel, because the gel becomes less permeable with increasing rigidity. To resolve this challenge, this study demonstrates a unique method to enhance the permeability of a cell-laden hydrogel while avoiding a significant change in rigidity of the gel. Inspired by the grooved skin textures of marine organisms, a hydrogel is assembled to present computationally optimized micro-sized grooves on the surface. Separately, a gel is engineered to preset aligned microchannels similar to a plant's vascular bundles through a uniaxial freeze-drying process. The resulting gel displays significantly increased water diffusivity with reduced changes of gel stiffness, exclusively when the microgrooves and microchannels are aligned together. No significant enhancement of rehydration is achieved when the microgrooves and microchannels are not aligned. Such material design greatly enhances viability and neural differentiation of stem cells and 3D neural network formation within the gel.
Deepwater Gulf of Mexico turbidites -- Compaction effects on porosity and permeability
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ostermeier, R.M.
1995-06-01
The deepwater Gulf of Mexico is now a major area of activity for the US oil industry. Compaction causes particular concern because most prospective deepwater reservoirs are highly geo-pressured and many have limited aquifer support; water injection may also be problematic. To address some of the issues associated with compaction, the authors initiated a special core-analysis program to study compaction effects on turbidite sand porosity and permeability specifically. This program also addressed a number of subsidiary but no less important issues, such as sample characterization and quality, sample preparation, and test procedures. These issues are particularly pertinent, because Gulf ofmore » Mexico turbidites are generally unconsolidated, loose sands, and are thus susceptible to a whole array of potentially serious core-disturbing processes. One key result of the special core analysis program is that turbidite compressibilities exhibit large variations in both magnitude and stress dependence. These variations correlate with creep response in the laboratory measurements. The effects of compaction on permeability are significant. To eliminate complicating effects caused by fines movement, the authors made oil flow measurements at initial water saturation. The measurements indicate compaction reduces permeability four to five times more than porosity on a relative basis.« less
Regulation of AQP0 water permeability is enhanced by cooperativity
Németh-Cahalan, Karin L.; Clemens, Daniel M.
2013-01-01
Aquaporin 0 (AQP0), essential for lens clarity, is a tetrameric protein composed of four identical monomers, each of which has its own water pore. The water permeability of AQP0 expressed in Xenopus laevis oocytes can be approximately doubled by changes in calcium concentration or pH. Although each monomer pore functions as a water channel, under certain conditions the pores act cooperatively. In other words, the tetramer is the functional unit. In this paper, we show that changes in external pH and calcium can induce an increase in water permeability that exhibits either a positive cooperativity switch-like increase in water permeability or an increase in water permeability in which each monomer acts independently and additively. Because the concentrations of calcium and hydrogen ions increase toward the center of the lens, a concentration signal could trigger a regulatory change in AQP0 water permeability. It thus seems plausible that the cooperative modes of water permeability regulation by AQP0 tetramers mediated by decreased pH and elevated calcium are the physiologically important ones in the living lens. PMID:23440275
PERMEABLE TREATMENT WALL EFFECTIVENESS MONITORING PROJECT, NEVADA STEWART MINE
This report summarizes the results of Mine Waste Technology Program (MWTP) Activity III, Project 39, Permeable Treatment Wall Effectiveness Monitoring Project, implemented and funded by the U.S. Environmental Protection Agency (EPA) and jointly administered by EPA and the U.S. De...
Enhancement of scleral macromolecular permeability with prostaglandins.
Weinreb, R N
2001-01-01
PURPOSE: It is proposed that the sclera is a metabolically active and pharmacologically responsive tissue. These studies were undertaken to determine whether prostaglandin exposure can enhance scleral permeability to high-molecular-weight substances. METHODS: Topical prostaglandin F2 alpha (PGF2 alpha) was administered to monkeys to determine if this altered the amount of scleral matrix metalloproteinases (MMPs). Experiments also were performed to determine whether the prostaglandin F (FP) receptor and gene transcripts are expressed in normal human sclera. Permeability of organ-cultured human sclera following prostaglandin exposure then was studied and the amount of MMP released into the medium measured. Finally, the permeability of human sclera to basic fibroblast growth factor (FGF-2) was determined following prostaglandin exposure. RESULTS: Topical prostaglandin administration that reduced scleral collagen also increased scleral MMP-1, MMP-2, and MMP-3 by 63 +/- 35%, 267 +/- 210%, and 729 +/- 500%, respectively. FP receptor protein was localized in scleral fibroblasts, and FP receptor gene transcript was identified in sclera. Exposure to prostaglandin F2 alpha, 17-phenyltrinor, PGF2 alpha, or latanoprost acid increased scleral permeability by up to 124%, 183%, or 213%, respectively. In these cultures, MMP-1, MMP-2, and MMP-3 were increased by up to 37%, 267%, and 96%, respectively. Finally, transscleral absorption of FGF-2 was increased by up to 126% with scleral exposure to latanoprost. CONCLUSIONS: These studies demonstrate that the sclera is metabolically active and pharmacologically responsive to prostaglandins. Further, they demonstrate the feasibility of cotreatment with prostaglandin to enhance transscleral delivery of peptides, such as growth factors and high-molecular-weight substances, to the posterior segment of the eye. PMID:11797317
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.
Microscale diffusion measurements and simulation of a scaffold with a permeable strut.
Lee, Seung Youl; Lee, Byung Ryong; Lee, Jongwan; Kim, Seongjun; Kim, Jung Kyung; Jeong, Young Hun; Jin, Songwan
2013-10-10
Electrospun nanofibrous structures provide good performance to scaffolds in tissue engineering. We measured the local diffusion coefficients of 3-kDa FITC-dextran in line patterns of electrospun nanofibrous structures fabricated by the direct-write electrospinning (DWES) technique using the fluorescence recovery after photobleaching (FRAP) method. No significant differences were detected between DWES line patterns fabricated with polymer supplied at flow rates of 0.1 and 0.5 mL/h. The oxygen diffusion coefficients of samples were estimated to be ~92%-94% of the oxygen diffusion coefficient in water based on the measured diffusion coefficient of 3-kDa FITC-dextran. We also simulated cell growth and distribution within spatially patterned scaffolds with struts consisting of either oxygen-permeable or non-permeable material. The permeable strut scaffolds exhibited enhanced cell growth. Saturated depths at which cells could grow to confluence were 15% deeper for the permeable strut scaffolds than for the non-permeable strut scaffold.
NASA Astrophysics Data System (ADS)
Lorenz, John C.; Warpinski, Norman R.; Teufel, Lawrence W.; Branagan, Paul T.; Sattler, Allan R.; Northrop, David A.
Hundreds of millions of cubic meters of natural gas are locked up in low-permeability, natural gas reservoirs. The Multiwell Experiment (MWX) was designed to characterize such reservoirs, typical of much of the western United States, and to assess and develop a technology for the production of this unconventional resource. Flow-rate tests of the MWX reservoirs indicate a system permeability that is several orders of magnitude higher than laboratory permeability measurements made on matrix-rock sandstones. This enhanced permeability is caused by natural fractures. The single set of fractures present in the reservoirs provides a significant permeability anisotropy that is aligned with the maximum in situ horizontal stress. Hydraulic fractures therefore form parallel to the natural fractures and are consequently an inefficient mechanism for stimulation. Successful stimulation may be possible by perturbing the local stress field with a large hydraulic fracture in one well so that a second hydraulic fracture in an offset well propagates transverse to the natural fracture permeability trend.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hong, Tao; Chatterjee, Sabornie; Mahurin, Shannon M.
Amidoxime-functionalized polydimethylsiloxane (AO-PDMSPNB) membranes with various amidoxime compositions were synthesized via ring-opening metathesis polymerization followed by post-polymerization modification. Compared to other previously reported PDMS-based membranes, the amidoxime-functionalized membranes show enhanced CO 2 permeability and CO 2/N 2 selectivity. The overall gas separation performance (CO 2 permeability 6800 Barrer; CO 2/N 2 selectivity 19) of the highest performing membrane exceeds the Robeson upper bound line, and the excellent permeability of the copolymer itself provides great potential for real world applications where huge volumes of gases are separated. This study details how tuning the CO 2-philicity within rubbery polymer matrices influences gasmore » transport properties. Key parameters for tuning gas transport properties are discussed, and the experimental results show good consistency with theoretical calculations. Finally, this study provides a roadmap to enhancing gas separation performance in rubbery polymers by tuning gas solubility selectivity.« less
Enhanced Wireless Power Transmission Using Strong Paramagnetic Response.
Ahn, Dukju; Kiani, Mehdi; Ghovanloo, Maysam
2014-03-01
A method of quasi-static magnetic resonant coupling has been presented for improving the power transmission efficiency (PTE) in near-field wireless power transmission, which improves upon the state of the art. The traditional source resonator on the transmitter side is equipped with an additional resonator with a resonance frequency that is tuned substantially higher than the magnetic field excitation frequency. This additional resonator enhances the magnetic dipole moment and the effective permeability of the power transmitter, owing to a phenomenon known as the strong paramagnetic response. Both theoretical calculations and experimental results show increased PTE due to amplification of the effective permeability. In measurements, the PTE was improved from 57.8% to 64.2% at the nominal distance of 15 cm when the effective permeability was 2.6. The power delivered to load was also improved significantly, with the same 10 V excitation voltage, from 0.38 to 5.26 W.
NASA Astrophysics Data System (ADS)
Watanabe, Noriaki; Egawa, Motoki; Sakaguchi, Kiyotoshi; Ishibashi, Takuya; Tsuchiya, Noriyoshi
2017-06-01
Hydraulic fracturing experiments were conducted at 200-450°C by injecting water into cylindrical granite samples containing a borehole at an initial effective confining pressure of 40 MPa. Intensive fracturing was observed at all temperatures, but the fracturing characteristics varied with temperature, perhaps due to differences in the water viscosity. At the lowest considered temperature (200°C), fewer fractures propagated linearly from the borehole, and the breakdown pressure was twice the confining pressure. However, these characteristics disappeared with increasing temperature; the fracture pattern shifted toward the formation of a greater number of shorter fractures over the entire body of the sample, and the breakdown pressure decreased greatly. Hydraulic fracturing significantly increased the permeability at all temperatures, and this permeability enhancement was likely to form a productive geothermal reservoir even at the highest considered temperature, which exceeded both the brittle-ductile transition temperature of granite and the critical temperature of water.
Application of Layered Perforation Profile Control Technique to Low Permeable Reservoir
NASA Astrophysics Data System (ADS)
Wei, Sun
2018-01-01
it is difficult to satisfy the demand of profile control of complex well section and multi-layer reservoir by adopting the conventional profile control technology, therefore, a research is conducted on adjusting the injection production profile with layered perforating parameters optimization. i.e. in the case of coproduction for multi-layer, water absorption of each layer is adjusted by adjusting the perforating parameters, thus to balance the injection production profile of the whole well section, and ultimately enhance the oil displacement efficiency of water flooding. By applying the relationship between oil-water phase percolation theory/perforating damage and capacity, a mathematic model of adjusting the injection production profile with layered perforating parameters optimization, besides, perforating parameters optimization software is programmed. Different types of optimization design work are carried out according to different geological conditions and construction purposes by using the perforating optimization design software; furthermore, an application test is done for low permeable reservoir, and the water injection profile tends to be balanced significantly after perforation with optimized parameters, thereby getting a good application effect on site.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brownlow, D.T.; Escude, S.; Johanneson, O.H.
The 1500 Area at Kelly Air Force Base (AFB) was the site of a subsurface release of approximately 1,000 gallons of JP-4 jet fuel. Preliminary studies found evidence of hydrocarbon contamination extending from 10 feet below ground surface (bgs) down to the shallow water table, at 20 to 25 feet bgs. In June of 1993, Kelly AFB authorized the installation and evaluation of a bioventing system at this site to aid in the cleanup of the hydrocarbon contaminated soils. The purpose of the bioventing system is to aerate subsurface soils within and immediately surrounding the release area, in order tomore » stimulate in-situ biological activity and enhance the natural bioremediation capacity of the soil. Augmenting oxygen to the indigenous soil microorganisms promotes the aerobic metabolism of fuel hydrocarbons in the soil. In vadose zone soils exhibiting relatively good permeability, bioventing has proven to be a highly cost effective remediation technology for treating fuel contaminated soils. In November, 1993, a Start-Up Test program consisting of an In-Situ Respiration Test (ISRT) and an Air Permeability Test was performed at the 1500 Area Spill Site.« less
Dahan, Arik; Miller, Jonathan M
2012-06-01
While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two have been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques: what are we doing to the apparent permeability when we increase the solubility? Permeability is equal to the drug's diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting a certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this paper, we describe the research that has been done thus far, and present new data, to shed light on this solubility-permeability interplay. It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods. Overall, the weight of the evidence indicates that the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulting absorption, and hence, the solubility-permeability interplay must be taken into account to strike the optimal solubility-permeability balance, in order to maximize the overall absorption.
Pump and treat in low permeability media
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mackay, D.M.
1996-08-01
Pump and Treat (P&T) is a commonly applied technology whose primary promise for the low permeability environments of interest to these technology reviews is almost certainly containment of the problem. Conventional P&T would be expected to offer little promise of complete restoration in such environments, unless very long time frames (decades or centuries) are considered. A variety of approaches have been proposed to enhance the efficiency of P&T; some appear to offer little promise in low or mixed permeability environments, while others may offer more promise (e.g. hydro- or pneumatic-fracturing, which are described elsewhere in this document, and application ofmore » vacuum to the extraction well(s), which is a proprietary technology whose promise is currently difficult to assess objectively). Understanding the potential advantages and means of optimizing these enhancement approaches requires more understanding of the basic processes limiting P&T performance in low or mixed permeability media. These efforts are probably also necessary to understand the advantages and means of optimizing many of the very different remedial technologies that may be applicable to low or mixed permeability environments. Finally, since a reasonably certain capability of P&T is containment (i.e. prevention of further migration of contaminants), P&T may generally be required as a sort of safety net around sites at which the alternative technologies are being tested or applied. 23 refs.« less
Xu, Shixin; Xu, Zhiliang; Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark
2017-11-01
Thromboembolism, one of the leading causes of morbidity and mortality worldwide, is characterized by formation of obstructive intravascular clots (thrombi) and their mechanical breakage (embolization). A novel two-dimensional multi-phase computational model is introduced that describes active interactions between the main components of the clot, including platelets and fibrin, to study the impact of various physiologically relevant blood shear flow conditions on deformation and embolization of a partially obstructive clot with variable permeability. Simulations provide new insights into mechanisms underlying clot stability and embolization that cannot be studied experimentally at this time. In particular, model simulations, calibrated using experimental intravital imaging of an established arteriolar clot, show that flow-induced changes in size, shape and internal structure of the clot are largely determined by two shear-dependent mechanisms: reversible attachment of platelets to the exterior of the clot and removal of large clot pieces. Model simulations predict that blood clots with higher permeability are more prone to embolization with enhanced disintegration under increasing shear rate. In contrast, less permeable clots are more resistant to rupture due to shear rate-dependent clot stiffening originating from enhanced platelet adhesion and aggregation. These results can be used in future to predict risk of thromboembolism based on the data about composition, permeability and deformability of a clot under specific local haemodynamic conditions. © 2017 The Author(s).
Kaiser, Mathias; Chalapala, Sudharani; Gorzelanny, Christian; Perali, Ramu Sridhar; Goycoolea, Francisco Martin
2016-02-01
Capsaicin is known to interfere with tight junctions (TJs) of epithelial cells and therefore to enhance paracellular permeability of poorly absorbable drugs. However, due to its low water solubility, pungency, and cytotoxicity, its pharmacologic use is limited. In this study, we investigated the effect of capsaicin derivatives of synthetic (e.g., 10-hydroxy-N-(4-hydroxy-3-methoxybenzyl)decanamide, etc.) and natural (olvanil and dihydrocapsaicin) origin on Madin-Darby Canine Kidney-C7 cells. Impedance spectroscopy was used to determine the transepithelial electrical resistance and the capacitance. Permeability assays with fluorescein isothiocyanate-dextran were carried out to evaluate the impact on cell permeability. The results show that lipophilicity could play an important role for the interference with TJ and that the mechanism is independent from the ion channel TRPV-1 and hence on the flux of calcium into the cells. In summary, we synthesized 4 derivatives of capsaicin of lower lipophilicity and compared their properties with other well-known vanilloids. We show that these compounds are able to enhance the permeability of a hydrophilic macromolecule, by opening the TJ for a shorter time than capsaicin. This behavior is dependent on the lipophilicity of the molecule. Understanding of these phenomena may lead to better control of administration of therapeutic molecules. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Nhan, Tam; Burgess, Alison; Cho, Eunice E.; Stefanovic, Bojana; Lilge, Lothar; Hynynen, Kullervo
2013-01-01
Reversible and localized blood-brain barrier disruption (BBBD) using focused ultrasound (FUS) in combination with intravascularly administered microbubbles (MBs) has been established as a non-invasive method for drug delivery to the brain. Using two-photon fluorescence microscopy (2PFM), we imaged the cerebral vasculature during BBBD and observed the extravasation of fluorescent dye in real-time in vivo. We measured the enhanced permeability upon BBBD for both 10kDa and 70kDa dextran conjugated Texas Red (TR) at the acoustic pressure range of 0.2-0.8 MPa and found permeability constants of TR10kDa and TR70kDa vary from 0.0006 to 0.0359 min−1 and 0.0003 to 0.0231 min−1, respectively. For both substances, a linear regression was applied on the permeability constant against the acoustic pressure and the slope from best-fit was found to be 0.039±0.005 min−1/MPa and 0.018±0.005 min−1/MPa, respectively. In addition, the pressure threshold for successfully induced BBBD was confirmed to be 0.4-0.6 MPa. Finally, we identified two types of leakage kinetics (fast and slow) that exhibit distinct permeability constants and temporal disruption onsets, as well as demonstrated their correlations with the applied acoustic pressure and vessel diameter. Direct assessment of vascular permeability and insights on its dependency on acoustic pressure, vessel size and leakage kinetics are important for treatment strategies of BBBD-based drug delivery. PMID:24008151
Yamane, Takehiro; Hanaoka, Kenjiro; Muramatsu, Yasuaki; Tamura, Keita; Adachi, Yusuke; Miyashita, Yasushi; Hirata, Yasunobu; Nagano, Tetsuo
2011-11-16
Gadolinium ion (Gd(3+)) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in T(1)-weighted MR images. Recently, several methods to achieve cell-permeation of Gd(3+) complexes have been reported, but more general and efficient methodology is needed. In this report, we describe a novel method to achieve cell permeation of Gd(3+) complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit. We synthesized Gd(3+) complexes conjugated with boron dipyrromethene (BDP-Gd) and Cy7 dye (Cy7-Gd), and showed that these conjugates can be introduced efficiently into cells. To examine the relationship between cell permeability and dye structure, we further synthesized a series of Cy7-Gd derivatives. On the basis of MR imaging, flow cytometry, and ICP-MS analysis of cells loaded with Cy7-Gd derivatives, highly hydrophobic and nonanionic dyes were effective for enhancing cell permeation of Gd(3+) complexes. Furthermore, the behavior of these Cy7-Gd derivatives was examined in mice. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to improve the cell permeability of Gd(3+) complexes, and should be applicable for further development of Gd(3+)-based MRI contrast agents.
Rathfelder, K M; Abriola, L M; Taylor, T P; Pennell, K D
2001-04-01
A numerical model of surfactant enhanced solubilization was developed and applied to the simulation of nonaqueous phase liquid recovery in two-dimensional heterogeneous laboratory sand tank systems. Model parameters were derived from independent, small-scale, batch and column experiments. These parameters included viscosity, density, solubilization capacity, surfactant sorption, interfacial tension, permeability, capillary retention functions, and interphase mass transfer correlations. Model predictive capability was assessed for the evaluation of the micellar solubilization of tetrachloroethylene (PCE) in the two-dimensional systems. Predicted effluent concentrations and mass recovery agreed reasonably well with measured values. Accurate prediction of enhanced solubilization behavior in the sand tanks was found to require the incorporation of pore-scale, system-dependent, interphase mass transfer limitations, including an explicit representation of specific interfacial contact area. Predicted effluent concentrations and mass recovery were also found to depend strongly upon the initial NAPL entrapment configuration. Numerical results collectively indicate that enhanced solubilization processes in heterogeneous, laboratory sand tank systems can be successfully simulated using independently measured soil parameters and column-measured mass transfer coefficients, provided that permeability and NAPL distributions are accurately known. This implies that the accuracy of model predictions at the field scale will be constrained by our ability to quantify soil heterogeneity and NAPL distribution.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fernandez, Carlos A.; Shao, Hongbo; Bonneville, Alain
Abstract The primary challenge for the feasibility of enhanced geothermal systems (EGS) is to cost-effectively create high-permeability reservoirs inside deep crystalline bedrock. Although fracturing fluids are commonly used for oil/gas, standard fracturing methods are not developed or proven for EGS temperatures and pressures. Furthermore, the environmental impacts of currently used fracturing methods are only recently being determined. These authors recently reported an environmentally benign, CO2-activated, rheoreversible fracturing fluid that enhances permeability through fracturing due to in situ volume expansion and gel formation. The potential of this novel fracturing fluid is evaluated in this work towards its application at geothermal sitesmore » under different pH conditions. Laboratory-scale fracturing experiments using Coso Geothermal rock cores under different pH environments were performed followed by X-ray microtomography characterization. The results demonstrate that CO2-reactive aqueous solutions of environmentally amenable polyallylamine (PAA) consistently and reproducibly creates/propagates fracture networks through highly impermeable crystalline rock from Coso EGS sites at considerably lower effective stress as compared to conventional fracturing fluids. In addition, permeability was significantly enhanced in a wide range of formation-water pH values. This effective, and environmentally-friendly fracturing fluid technology represents a potential alternative to conventional fracturing fluids.« less
Dynamo Enhancement and Mode Selection Triggered by High Magnetic Permeability.
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.
Evaluation of the permeability of agricultural films to various fumigants.
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.
Investigation of negative permeability metamaterials for wireless power transfer
NASA Astrophysics Data System (ADS)
Xin, Wenhui; Mi, Chunting Chris; He, Fei; Jiang, Meng; Hua, Dengxin
2017-11-01
In order to enhance the transmission efficiency of wireless power transfer (WPT), a negative permeability metamaterials (NPM) with a structure of honeycomb composed by units of hexagon-shaped spirals copper is proposed in this paper. The unit parameters of the NPM are optimized, to make sure the negative permeability at the special frequency. The S-parameters of the designed NPM are measured by a network analyzer and the permeability is extracted, it shows the honeycomb NPM has a negative permeability at 6.43 MHz. A two-coil WPT is setup and the transmission efficiency of WPT embedded with NPM at the different position and with different structure are investigated. The measured results show that the 2-slab honeycomb NPM have a good perform compared with the 1-slab NPM, and the efficiency can be increased up to 51%. The results show that honeycomb NPM embedded in the WPT help to improve the transmission efficiency remarkable.
Naga, Kranthi Kumari
2012-01-01
Dimebon was originally introduced as an antihistamine and subsequently investigated as a possible therapeutic for a variety of disorders, including Alzheimer's disease. One putative mechanism underlying the neuroprotective properties of Dimebon is inhibition of mitochondrial permeability transition, based on the observation that Dimebon inhibited the swelling of rat liver mitochondria induced by calcium and other agents that induce permeability transition. Because liver and brain mitochondria differ substantially in their properties and response to conditions associated with opening of the permeability transition pore, we sought to determine whether Dimebon inhibited permeability transition in brain mitochondria. Dimebon reduced calcium-induced mitochondrial swelling but did not enhance the calcium retention capacity or impair calcium-induced cytochrome C release from non-synaptic mitochondria isolated from rat brain cerebral cortex. These findings indicate that Dimebon does not inhibit mitochondrial permeability transition, induced by excessive calcium uptake, in brain mitochondria. PMID:20625939
Naga, Kranthi Kumari; Geddes, James W
2011-03-01
Dimebon was originally introduced as an antihistamine and subsequently investigated as a possible therapeutic for a variety of disorders, including Alzheimer's disease. One putative mechanism underlying the neuroprotective properties of Dimebon is inhibition of mitochondrial permeability transition, based on the observation that Dimebon inhibited the swelling of rat liver mitochondria induced by calcium and other agents that induce permeability transition. Because liver and brain mitochondria differ substantially in their properties and response to conditions associated with opening of the permeability transition pore, we sought to determine whether Dimebon inhibited permeability transition in brain mitochondria. Dimebon reduced calcium-induced mitochondrial swelling but did not enhance the calcium retention capacity or impair calcium-induced cytochrome C release from non-synaptic mitochondria isolated from rat brain cerebral cortex. These findings indicate that Dimebon does not inhibit mitochondrial permeability transition, induced by excessive calcium uptake, in brain mitochondria.
Glycosylation facilitates transdermal transport of macromolecules
Pino, Christopher J.; Gutterman, Jordan U.; Vonwil, Daniel; Mitragotri, Samir; Shastri, V. Prasad
2012-01-01
Stratum corneum, the outermost layer of skin, allows transport of only low-molecular weight (<500) lipophilic solutes. Here, we report a surprising finding that avicins (Avs), a family of naturally occurring glycosylated triterpenes with a molecular weight > 2,000, exhibit skin permeabilities comparable to those of small hydrophobic molecules, such as estradiol. Systematic fragmentation of the Av molecule shows that deletion of the outer monoterpene results in a 62% reduction in permeability, suggesting an important role for this motif in skin permeation. Further removal of the tetrasaccharide residue results in a further reduction of permeability by 79%. These results, taken in sum, imply that synergistic effects involving both hydrophobic and hydrophilic residues may hold the key in facilitating translocation of Avs across skin lipids. In addition to exhibiting high permeability, Avs provided moderate enhancements of skin permeability of estradiol and polysaccharides, including dextran and inulin but not polyethylene glycol. PMID:23236155
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
Transport of bacteria in porous media; 1: An experimental investigation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sarkar, A.K.; Georgiou, G.; Sharma, M.M.
1994-08-05
The convective transport of concentrated suspensions of bacteria in porous media is of interest for several processes such as microbial enhanced oil recovery and in situ bioremediation. The parameters which affect the transport of the bacterium Bacillus licheniformis JF-2, a candidate microorganism for microbial enhanced oil recovery, were investigated experimentally in sandpacks. Bacteria retention and permeability reduction occurred primarily in the first few centimeters upon entering the porous medium. In downstream sections of the sandpack, the permeability reduction was low, even in cases in which high cell concentrations were detected in the effluent. The effects of (1) addition of amore » dispersant, (2) linear velocity of injection, (3) cell concentration, (4) salinity, (5) temperature, and (6) the presence of a residual oleic phase were determined experimentally. A lower reduction in permeability and a higher effluent bacterial concentration were obtained in the presence of dispersant, high injection velocities, low salinities, and at a higher temperature. Macroscopic measurements at different linear velocities and in the presence or absence of dispersants suggest that the formation of reversible microaggregates and multiparticle hydrodynamic exclusion may be the primary mechanisms for bacterial retention and permeability reduction.« less
Sakuma, Shinji; Suita, Masaya; Yamamoto, Takafumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Nakajima, Noriko; Shinkai, Norihiro; Yamauchi, Hitoshi; Hiwatari, Ken-Ichiro; Hashizume, Akio; Tachikawa, Hiroyuki; Kimura, Ryoji; Ishimaru, Yuki; Kasai, Atsushi; Maeda, Sadaaki
2012-05-01
We are investigating a new class of penetration enhancers that enable poorly membrane-permeable molecules physically mixed with them to effectively penetrate cell membranes without their concomitant cellular uptake. Since we previously revealed that poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, significantly enhanced the nasal absorption of insulin, we examined the performance of the polymers on cell membranes. When Caco-2 cells were incubated with 5(6)-carboxyfluorescein (CF) for 30 min, approximately 0.1% of applied CF was internalized into the cells. This poor membrane permeability was dramatically enhanced by d-octaarginine-linked polymers; a 25-fold increase in the cellular uptake of CF was observed when the polymer concentration was adjusted to 0.2mg/mL. None of the individual components, for example, d-octaarginine, had any influence on CF uptake, demonstrating that only d-octaarginine anchored chemically to the polymeric platform enhanced the membrane permeation of CF. The polymer-induced CF uptake was consistently high even when the incubation time was extended to 120 min. Confocal laser scanning microphotographs of cells incubated with d-octaarginine-linked polymers bearing rhodamine red demonstrated that the cell outline was stained with red fluorescence. The polymer-induced CF uptake was significantly suppressed by 5-(N-ethyl-N-isopropyl)amiloride, which is an inhibitor of macropinocytosis. Results indicated that d-octaarginine-linked polymers remained on the cell membrane and poorly membrane-permeable CF was continuously internalized into cells mainly via macropinocytosis repeated for the individual peptidyl branches in the polymer backbone. Copyright © 2012 Elsevier B.V. All rights reserved.
Yamamoto, Shoshiro; Kato, Akari; Sakurai, Yu; Hada, Tomoya; Harashima, Hideyoshi
2017-04-10
The vascular endothelial growth factor (VEGF)-mediated enhancement in vascular permeability is considered to be a major factor in tumor-targeting delivery via the enhanced permeability and retention (EPR) effect. We previously reported that the silencing of the endothelial VEGF receptor (VEGFR2) by a liposomal siRNA system (RGD-MEND) resulted in an enhanced intratumoral distribution of polyethylene glycol (PEG)-modified liposomes (LPs) in a renal cell carcinoma, a type of hypervascularized cancer, although the inhibition of VEGF signaling would be expected to decrease the permeability of the tumor vasculature. We herein report that the enhancement in the intratumoral distribution of LPs by VEGFR2 inhibition was dependent on the vascular type of the tumor (stroma vessel type; SV and tumor vessel type; TV). In the case of TV-type tumors (renal cell carcinoma and hepatocellular carcinoma), inhibiting VEGFR2 improved intratumoral distribution, while no effect was found in the case of SV-type tumors (colorectal cancer). Moreover, through a comparison of the intratumoral distribution of LPs with a variety of physical properties (100nm vs 400nm, neutral vs negative vs positive), VEGFR2 inhibition was found to alter the tumor microenvironment, including heparan sulfate proteoglycans (HSPGs). In addition, the results regarding the effect of the size of nanoparticles indicated that VEGFR2 inhibition improved the penetration of nanoparticles through the vessel wall, but not via permeability, suggesting the involvement of an unknown mechanism. Our findings suggest that a combination of anti-angiogenic therapy and delivery via the EPR effect would be useful in certain cases, and that altering the tumor microenvironment by VEGFR2 blockade has a drastic effect on the intratumoral distribution of nanoparticles. Copyright © 2017 Elsevier B.V. All rights reserved.
Alkyl Pyrocarbonate Electrolyte Additives for Performance Enhancement of Li Ion Cells
NASA Technical Reports Server (NTRS)
Smart, M. C.; Ratnakumar, B. V.; Surampudi, S.
2000-01-01
Lithium ion rechargeable batteries are being developed for various aerospace applications under a NASA-DoD Interagency program. These applications require further improvements in several areas, specifically in the cycle life for LEO and GEO satellites and in the low temperature performance for the Mars Lander and Rover missions. Accordingly, we have been pursuing research studies to achieve improvement in the low temperature performance, long cycle life and active life of Li ion cells. The studies are mainly focused on electrolytes, to identify newer formulations of new electrolyte additives to enhance Li permeability (at low temperatures) and stability towards the electrode. The latter approach is particularly aimed at the formation suitable SEI (solid electrolyte interphase) on carbon electrodes. In this paper, we report the beneficial effect of using alkyl pyrocarbonates as electrolyte additives to improve the low temperature performance of Li ion cells.
Sanphui, Palash; Devi, V Kusum; Clara, Deepa; Malviya, Nidhi; Ganguly, Somnath; Desiraju, Gautam R
2015-05-04
Hydrochlorothiazide (HCT) is a diuretic and a BCS class IV drug with low solubility and low permeability, exhibiting poor oral absorption. The present study attempts to improve the physicochemical properties of the drug using a crystal engineering approach with cocrystals. Such multicomponent crystals of HCT with nicotinic acid (NIC), nicotinamide (NCT), 4-aminobenzoic acid (PABA), succinamide (SAM), and resorcinol (RES) were prepared using liquid-assisted grinding, and their solubilities in pH 7.4 buffer were evaluated. Diffusion and membrane permeability were studied using a Franz diffusion cell. Except for the SAM and NIC cocrystals, all other binary systems exhibited improved solubility. All of the cocrystals showed improved diffusion/membrane permeability compared to that of HCT with the exception of the SAM cocrystal. When the solubility was high, as in the case of PABA, NCT, and RES cocrystals, the flux/permeability dropped slightly. This is in agreement with the expected interplay between solubility and permeability. Improved solubility/permeability is attributed to new drug-coformer interactions. Cocrystals of SAM, however, showed poor solubility and flux. This cocrystal contains a primary sulfonamide dimer synthon similar to that of HCT polymorphs, which may be a reason for its unusual behavior. Hirshfeld surface analysis was carried out in all cases to determine whether a correlation exists between cocrystal permeability and drug-coformer interactions.
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.
Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol.
Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival
2016-10-10
To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colonic permeability was determined in rat colon using in situ closed loop perfusion method based in Doluisio's Technique. To check the potential effects of the counter ions on the membrane integrity, a histological assessment of colonic tissue was done. The results of the partitioning studies were inconclusive about ion-pair formation; nevertheless colon permeability was significantly increased by both counter ions (from 0.232±0.021cm/s to 0.508±0.038cm/s in the presence of brilliant blue and to 0.405±0.044cm/s in the presence of bromophenol blue). Neither damage on the membrane was observed on the histological studies, nor any change on paracellular permeability suggesting that the permeability enhancement could be attributed to the ion-pair formation. Copyright © 2016 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhong, Lirong; Oostrom, Martinus; Wietsma, Thomas W.
2008-07-29
Abstract Heterogeneity is often encountered in subsurface contamination characterization and remediation. Low-permeability zones are typically bypassed when remedial fluids are injected into subsurface heterogeneous aquifer systems. Therefore, contaminants in the bypassed areas may not be contacted by the amendments in the remedial fluid, which may significantly prolong the remediation operations. Laboratory experiments and numerical studies have been conducted to develop the Mobility-Controlled Flood (MCF) technology for subsurface remediation and to demonstrate the capability of this technology in enhancing the remedial amendments delivery to the lower permeability zones in heterogeneous systems. Xanthan gum, a bio-polymer, was used to modify the viscositymore » of the amendment-containing remedial solutions. Sodium mono-phosphate and surfactant were the remedial amendment used in this work. The enhanced delivery of the amendments was demonstrated in two-dimensional (2-D) flow cell experiments, packed with heterogeneous systems. The impact of polymer concentration, fluid injection rate, and permeability contract in the heterogeneous systems has been studied. The Subsurface Transport over Multiple Phases (STOMP) simulator was modified to include polymer-induced shear thinning effects. Shear rates of polymer solutions were computed from pore-water velocities using a relationship proposed in the literature. Viscosity data were subsequently obtained from empirical viscosity-shear rate relationships derived from laboratory data. The experimental and simulation results clearly show that the MCF technology is capable of enhancing the delivery of remedial amendments to subsurface lower permeability zones. The enhanced delivery significantly improved the NAPL removal from these zones and the sweeping efficiency on a heterogeneous system was remarkably increased when a polymer fluid was applied. MCF technology is also able to stabilize the fluid displacing front when there is a density difference between the fluids. The modified STOMP simulator was able to predict the experimental observed fluid displacing behavior. The simulator may be used to predict the subsurface remediation performance when a shear thinning fluid is used to remediate a heterogeneous system.« less
Numerical simulation based on core analysis of a single fracture in an Enhanced Geothermal System
NASA Astrophysics Data System (ADS)
Jarrahi, Miad; Holländer, Hartmut
2017-04-01
The permeability of reservoirs is widely affected by the presence of fractures dispersed within them, as they form superior paths for fluid flow. Core analysis studies the fractures characteristics and explains the fluid-rock interactions to provide the information of permeability and saturation of a hydraulic fracturing reservoir or an enhanced geothermal system (EGS). This study conducted numerical simulations of a single fracture in a Granite core obtained from a depth of 1890 m in borehole EPS1 from Soultz-sous-Forêts, France. Blaisonneau et al. (2016) designed the apparatus to investigate the complex physical phenomena on this cylindrical sample. The method of the tests was to percolate a fluid through a natural fracture contained in a rock sample, under controlled thermo-hydro-mechanical conditions. A divergent radial flow within the fracture occurred due to the injection of fluid into the center of the fracture. The tests were performed within a containment cell with a normal stress of 2.6, 4.9, 7.2 and 9.4 MPa loading on the sample perpendicular to the fracture plane. This experiment was numerically performed to provide an efficient numerical method by modeling single phase flow in between the fracture walls. Detailed morphological features of the fracture such as tortuosity and roughness, were obtained by image processing. The results included injection pressure plots with respect to injection flow rate. Consequently, by utilizing Hagen-Poiseuille's cubic law, the equivalent hydraulic aperture size, of the fracture was derived. Then, as the sample is cylindrical, to modify the Hagen-Poiseuille's cubic law for circular parallel plates, the geometric relation was applied to obtain modified hydraulic aperture size. Finally, intrinsic permeability of the fracture under each mechanical normal stress was evaluated based on modified hydraulic aperture size. The results were presented in two different scenarios, before and after reactive percolation test, to demonstrate the effect of chemical reactive flow. The fracture after percolation test showed larger equivalent aperture size and higher permeability. Additionally, the higher the normal stress, the lower permeability was investigated. This confirmed the permeability evolution due to chemical percolation and mechanical loading. All results showed good agreements with corresponding experimental results provided by Blaisonneau et al. (2016). Keyword: Core analysis, Hydraulic fracturing, Enhanced geothermal system, Permeability, Fluid-rock interactions.
NASA Astrophysics Data System (ADS)
Gehne, Stephan; Benson, Philip M.
2017-08-01
Permeability in tight crustal rocks is primarily controlled by the connected porosity, shape and orientation of microcracks, the preferred orientation of cross-bedding, and sedimentary features such as layering. This leads to a significant permeability anisotropy. Less well studied, however, are the effects of time and stress recovery on the evolution of the permeability hysteresis which is becoming increasingly important in areas ranging from fluid migration in ore-forming processes to enhanced resource extraction. Here, we report new data simulating spatio-temporal permeability changes induced using effective pressure, simulating burial depth, on a tight sandstone (Crab Orchard). We find an initially (measured at 5 MPa) anisotropy of 2.5% in P-wave velocity and 180% in permeability anisotropy is significantly affected by the direction of the effective pressure change and cyclicity; anisotropy values decrease to 1% and 10% respectively after 3 cycles to 90 MPa and back. Furthermore, we measure a steadily increasing recovery time (10-20 min) for flow parallel to cross-bedding, and a far slower recovery time (20-50 min) for flow normal to cross-bedding. These data are interpreted via strain anisotropy and accommodation models, similar to the "seasoning" process often used in dynamic reservoir extraction.
Small, Ted A.; Clark, Allan K.
2000-01-01
The hydrogeologic subdivisions of the Edwards aquifer outcrop in Medina County generally are porous and permeable. The most porous and permeable appear to be hydrogeologic subdivision VI, the Kirschberg evaporite member of the Kainer Formation; and hydrogeologic subdivision III, the leached and collapsed members, undivided, of the Person Formation. The most porous and permeable rocks of the Devils River Formation in Medina County appear to be in the top layer. The upper member of the Glen Rose Limestone, the lower confining unit, has much less porosity and permeability than that observed in the Edwards aquifer.The Edwards aquifer has relatively large porosity and permeability resulting, in part, from the development or redistribution of secondary porosity. Lithology, stratigraphy, diagenesis, and karstification account for the effective porosity and permeability in the Edwards aquifer outcrop. Karst features that can greatly enhance effective porosity and permeability in the Edwards aquifer outcrop include sinkholes, dolines, and caves. The Edwards aquifer rocks in Medina County change from the eight-member Edwards Group to the essentially indivisible Devils River Formation. The facies change occurs along a line extending northwestward from just south of Medina Lake.
Research on the performance of sand-based environmental-friendly water permeable bricks
NASA Astrophysics Data System (ADS)
Cai, Runze; Mandula; Chai, Jinyi
2018-02-01
This paper examines the effects of the amount of admixture, the water cement ratio, the aggregate grading, and the cement aggregate ratio on the mechanical service properties and of porous concrete pavement bricks including strength, water permeability, frost resistance, and wear resistance. The admixture can enhance the performance of water permeable brick, and optimize the design mix. Experiments are conducted to determine the optimal mixing ratios which are given as; (1) the admixture (self-developed) within the content of 5% of the cement quality; (2) water-cement ratio equal to 0.34; (3) cement-aggregate ratio equal to 0.25; (4) fine aggregate of 70% (particle size 0.6-2.36mm); and coarse aggregate of 30% (particle size: 2.36-4.75mm). The experimental results that the sand-based permeable concrete pavement brick has a strength of 35.6MPa and that the water permeability coefficient is equal to 3.5×10-2cm/s. In addition, it was found that the concrete water permeable brick has good frost resistance and surface wear resistance, and that the its production costs are much lower than the similar sand-based water permeable bricks in China.
Zhang, Qun-Lin; Fu, Bingmei M; Zhang, Zhang-Jin
2017-11-01
The clinical application of central nervous system (CNS) drugs is limited by their poor bioavailability due to the blood-brain barrier (BBB). Borneol is a naturally occurring compound in a class of 'orifice-opening' agents often used for resuscitative purposes in traditional Chinese medicine. A growing body of evidence confirms that the 'orifice-opening' effect of borneol is principally derived from opening the BBB. Borneol is therefore believed to be an effective adjuvant that can improve drug delivery to the brain. The purpose of this paper is to provide a comprehensive review of information accumulated over the past two decades on borneol's chemical features, sources, toxic and kinetic profiles, enhancing effects on BBB permeability and their putative mechanisms, improvements in CNS drug delivery, and pharmaceutical forms. The BBB-opening effect of borneol is a reversible physiological process characterized by rapid and transient penetration of the BBB and highly specific brain regional distribution. Borneol also protects the structural integrity of the BBB against pathological damage. The enhancement of the BBB permeability is associated with the modulation of multiple ATP-binding cassette transporters, including P-glycoprotein; tight junction proteins; and predominant enhancement of vasodilatory neurotransmitters. Systemic co-administration with borneol improves drug delivery to the brain in a region-, dose- and time-dependent manner. Several pharmaceutical forms of borneol have been developed to improve the kinetic and toxic profiles of co-administered drugs and enhance their delivery to the brain. Borneol is a promising novel agent that deserves further development as a BBB permeation enhancer for CNS drug delivery.
NASA Astrophysics Data System (ADS)
Rutqvist, J.; Rinaldi, A. P.
2017-12-01
The exploitation of a geothermal system is one of the most promising clean and almost inexhaustible forms of energy production. However, the exploitation of hot dry rock (HDR) reservoirs at depth requires circulation of a large amount of fluids. Indeed, the conceptual model of an Enhanced Geothermal System (EGS) requires that the circulation is enhanced by fluid injection. The pioneering experiments at Fenton Hill demonstrated the feasibility of EGS by producing the world's first HDR reservoirs. Such pioneering project demonstrated that the fluid circulation can be effectively enhanced by stimulating a preexisting fracture zone. The so-called "hydroshearing" involving shear activation of preexisting fractures is recognized as one of the main processes effectively enhancing permeability. The goal of this work is to quantify the effect of shear reactivation on permeability by proposing a model that accounts for fracture opening and shearing. We develop a case base on a pressure stimulation experiment at Fenton Hill, in which observation suggest that a fracture was jacked open by pressure increase. The proposed model can successfully reproduce such a behavior, and we compare the base case of pure elastic opening with the hydroshearing model to demonstrate that this latter could have occurred at the field, although no "felt" seismicity was observed. Then we investigate on the sensitivity of the proposed model by varying some of the critical parameters such as the maximum aperture, the dilation angle, as well as the fracture density.
Influence of relative permeabilities on chemical enhanced oil recovery
NASA Astrophysics Data System (ADS)
Destefanis, M. F.; Savioli, G. B.
2011-05-01
The main objective of chemical flooding is to mobilize the trapped oil remaining after a secondary recovery by waterflooding. This purpose is achieved by lowering the oil-water interfacial tension and producing partial miscibility between both phases. The chemical partition among phases (phase behavior) influences all other physical properties. In particular, it affects residual saturations determining relative permeability curves. Relative permeabilities rule the flow of each phase through the porous medium, so they play an essential role in oil recovery. Therefore, in this work we study the influence of relative permeabilities on the behavior of a surfactant-polymer flooding for the three different types of phase behavior. This analysis is performed applying the 3D compositional numerical simulator UTCHEM developed at the University of Texas at Austin. From the examples studied, we conclude that the influence of relative permeabilities depends on the type of phase behavior, i.e., as microemulsion relative permeability decreases, oil recovery increases for Types II(+) and III while slightly decreases for Type II(-). Moreover, a better displacement efficiency is observed for Types II(+) and III, because they behave similarly to a miscible displacement.
Analysis of Selected Enhancements for Soil Vapor Extraction
1997-09-01
Inches per second ACRONYMS AND ABBREVIATIONS (Continued) xiii ISB In situ bioremediation JFK John F. Kennedy Airport K Hydraulic conductivity KAI KAI...wells by an applied vacuum. RFH is effective for treating VOCs in low-permeability soil in the vadose zone. Electrical Resistance Heating : This... applied vacuum. However, application of steam injection/stripping systems is limited to medium- to high-permeability soils. ER heating is more
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
Ultrasound-Enhanced Delivery of Antibiotics and Anti-Inflammatory Drugs into the Eye
Nabili, Marjan; Patel, Hetal; Mahesh, Sankaranarayana P.; Liu, Ji; Geist, Craig; Zderic, Vesna
2013-01-01
Delivery of sufficient amounts of therapeutic drugs into the eye is often a challenging task. In this study, ultrasound application (frequencies of 400 KHz to 1 MHz, intensities of 0.3–1.0 W/cm2 and exposure duration of 5 min) was investigated to overcome the barrier properties of cornea, which is a typical route for topical administration of ophthalmic drugs. Permeability of ophthalmic drugs, tobramycin and dexamethasone and sodium fluorescein, a drug-mimicking compound, was studied in ultrasound- and sham-treated rabbit corneas in vitro using a standard diffusion cell setup. Light microscopy observations were used to determine ultrasound-induced structural changes in the cornea. For tobramycin, an increase in permeability for ultrasound- and sham-treated corneas was not statistically significant. Increase of 46%–126% and 32%–109% in corneal permeability was observed for sodium fluorescein and dexamethasone, respectively, with statistical significance (p < 0.05) achieved at all treatment parameter combinations (compared with sham treatments) except for 1-MHz ultrasound applications for dexamethasone experiments. This permeability increase was highest at 400 kHz and appeared to be higher at higher intensities applied. Histologic analysis showed structural changes that were limited to epithelial layers of cornea. In summary, ultrasound application provided enhancement of drug delivery, increasing the permeability of the cornea for the anti-inflammatory ocular drug dexamethasone. Future investigations are needed to determine the effectiveness and safety of this application in in vivo long-term survival studies. (E-mail: mnabili@gwu.edu) PMID:23415283
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.
Ramundo-Orlando, Alfonsina; Serafino, Annalucia; Schiavo, Rosangela; Liberti, Micaela; d'Inzeo, Guglielmo
2005-02-01
The effect of extremely low frequency and low amplitude magnetic fields on gap junctional permeability was investigated by using reconstituted connexin32 hemi channel in liposomes. Cytochrome c was loaded inside these proteoliposomes and its reduction upon addition of ascorbate in the bulk aqueous phase was adopted as the index of hemi channel permeability. The permeability rate of the hemi channels, expressed as DeltaA/min, was dependent on the incubation temperature of proteoliposomes. The effect of exposures to magnetic fields at different frequencies (7, 13 and 18 Hz) and amplitudes (50, 50 and 70 microT, respectively), and at different temperatures (16, 18 and 24 degrees C) was studied. Only the exposure of proteoliposomes to 18-Hz (B(acpeak) and B(dc)=70 microT) magnetic field for 60 min at 16+/-0.4 degrees C resulted in a significant enhancement of the hemi channel permeability from DeltaA/min=0.0007+/-0.0002 to DeltaA/min=0.0010+/-0.0001 (P=0.030). This enhancement was not found for magnetic field exposures of liposomes kept at the higher temperatures tested. Temperature appears to influence lipid bilayer arrangement in such a way as being capable to mask possible effects induced by the magnetic field. Although the observed effect was very low, it seems to confirm the applicability of our model previously proposed for the interaction of low frequency electromagnetic fields with lipid membrane.
Wu, Chun-jie; Huang, Qin-wan; Qi, Hong-yi; Guo, Ping; Hou, Shi-xiang
2006-09-01
Studies on the influence of borneol on the penetration of puerarin eye drops and timolol maleate eye drops through the cornea, and evaluation of the ocular irritability were conducted to provide a theoretical basis for the application of borneol in enhancing corneal permeability. The cornea penetrative experiment in vitro was conducted to observe the quantitative change of puerarin and timolol maleate penetrated through the cornea after administering different dosages of borneol. The corneal hydration level and blinking frequency were recorded as irritability indexes in vitro and in vivo. The steady-flow J of high, middle and low dosage groups of puerarin eye drops with borneol were increased by 49%, 32%, 5% respectively, and permeability parameter Kp increased by 49%, 32%, 5% respectively, as compared to that of the control group. The steady-flow J of high dosage group of timolol maleate eye drops with borneol was increased by 5%; middle and low dosage groups with borneol were decreased by 6%, 3% respectively. The permeability parameter Kp of high dosage group increased by 5%, while middle and low dosage groups with borneol were decreased by 6%, 3% respectively, as compared to that of the control group. Evaluation showed no ocular irritability caused by borneol. The results of this study suggest that the promoting effect of borneol on the permeability of drugs through the cornea in vitro is selective, which indicates that borneol has the potential to be used as an ophthalmic penetration enhancer.
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.
Athukuri, Bhargavi Latha; Neerati, Prasad
2017-09-01
The oral bioavailability of diltiazem is very low due to rapid first pass metabolism in liver and intestine. The purpose of the study was to investigate the effect of gallic acid and ellagic acid on intestinal transport and oral bioavailability of diltiazem in rats. The intestinal transport and permeability of diltiazem was evaluated by in vitro non-everted sac method and in situ single pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study. The intestinal transport and apparent permeability of diltiazem were significantly enhanced in duodenum, jejunum, and ileum of gallic and ellagic acid-treated groups. The effective permeability of diltiazem was significantly enhanced in ileum part of gallic and ellagic acid-treated groups. When compared with control group, the presence of these two phytochemicals significantly enhanced the area under plasma concentration-time curve and the peak plasma concentration of diltiazem (C max ). Gallic acid and ellagic acid significantly increased the bioavailability of diltiazem due to the inhibition of both CYP3A-mediated metabolism and P-glycoprotein-mediated efflux in the intestine and/or liver. Based on these results, the clinical experiments are warranted for the confirmation to reduce the dose of diltiazem when concomitantly administered with these phytochemicals. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Gensure, Rebekah H.; Zeidel, Mark L.; Hill, Warren G.
2006-01-01
H+/OH− permeation through lipid bilayers occurs at anomalously high rates and the determinants of proton flux through membranes are poorly understood. Since all life depends on proton gradients, it is important to develop a greater understanding of proton leak phenomena. We have used stopped-flow fluorimetry to probe the influence of two lipid raft components, chol (cholesterol) and SM (sphingomyelin), on H+/OH− and water permeability. Increasing the concentrations of both lipids in POPC (palmitoyl-2-oleoyl phosphatidylcholine) liposomes decreased water permeability in a concentration-dependent manner, an effect that correlated with increased lipid order. Surprisingly, proton flux was increased by increasing the concentration of chol and SM. The chol effect was complex with molar concentrations of 17.9, 33 and 45.7% giving 2.8-fold (P<0.01), 2.2-fold (P<0.001) and 5.1-fold (P<0.001) increases in H+/OH− permeability from a baseline of 2.4×10−2 cm/s. SM at 10 mole% effected a 2.8-fold increase (P<0.01), whereas 20 and 30 mole% enhanced permeability by 3.6-fold (P<0.05) and 4.1-fold respectively (P<0.05). Supplementing membranes containing chol with SM did not enhance H+/OH− permeability. Of interest was the finding that chol addition to soya-bean lipids decreased H+/OH− permeability, consistent with an earlier report [Ira and Krishnamoorthy (2001) J. Phys. Chem. B 105, 1484–1488]. We speculate that the presence of proton carriers in crude lipid extracts might contribute to this result. We conclude that (i) chol and SM specifically and independently increase rates of proton permeation in POPC bilayers, (ii) domains enriched in these lipids or domain interfaces may represent regions with high H+/OH− conductivity, (iii) H+/OH− fluxes are not governed by lipid order and (iv) chol can inhibit or promote H+/OH− permeability depending on the total lipid environment. Theories of proton permeation are discussed in the light of these results. PMID:16706750
Internal hydrological mechanism of permeable pavement and interaction with subsurface water - slides
A permeable pavement site located at the Seitz Elementary School on Fort Riley, Kansas was selected for this study. An 80-space parking lot was built behind the school as part of an EPA ORD collaboration with the U.S. Army under the Net Zero program. The parking lot design includ...
Systems analysis of the CO2 concentrating mechanism in cyanobacteria
Mangan, Niall M; Brenner, Michael P
2014-01-01
Cyanobacteria are photosynthetic bacteria with a unique CO2 concentrating mechanism (CCM), enhancing carbon fixation. Understanding the CCM requires a systems level perspective of how molecular components work together to enhance CO2 fixation. We present a mathematical model of the cyanobacterial CCM, giving the parameter regime (expression levels, catalytic rates, permeability of carboxysome shell) for efficient carbon fixation. Efficiency requires saturating the RuBisCO reaction, staying below saturation for carbonic anhydrase, and avoiding wasteful oxygenation reactions. We find selectivity at the carboxysome shell is not necessary; there is an optimal non-specific carboxysome shell permeability. We compare the efficacy of facilitated CO2 uptake, CO2 scavenging, and HCO3− transport with varying external pH. At the optimal carboxysome permeability, contributions from CO2 scavenging at the cell membrane are small. We examine the cumulative benefits of CCM spatial organization strategies: enzyme co-localization and compartmentalization. DOI: http://dx.doi.org/10.7554/eLife.02043.001 PMID:24842993
Hong, Tao; Chatterjee, Sabornie; Mahurin, Shannon M.; ...
2017-02-22
Amidoxime-functionalized polydimethylsiloxane (AO-PDMSPNB) membranes with various amidoxime compositions were synthesized via ring-opening metathesis polymerization followed by post-polymerization modification. Compared to other previously reported PDMS-based membranes, the amidoxime-functionalized membranes show enhanced CO 2 permeability and CO 2/N 2 selectivity. The overall gas separation performance (CO 2 permeability 6800 Barrer; CO 2/N 2 selectivity 19) of the highest performing membrane exceeds the Robeson upper bound line, and the excellent permeability of the copolymer itself provides great potential for real world applications where huge volumes of gases are separated. This study details how tuning the CO 2-philicity within rubbery polymer matrices influences gasmore » transport properties. Key parameters for tuning gas transport properties are discussed, and the experimental results show good consistency with theoretical calculations. Finally, this study provides a roadmap to enhancing gas separation performance in rubbery polymers by tuning gas solubility selectivity.« less
Goh, Vicky; Halligan, Steve; Hugill, Jo-Ann; Gartner, Louise; Bartram, Clive I
2005-01-01
To determine the effect of acquisition time on quantitative colorectal cancer perfusion measurement. Dynamic contrast-enhanced computed tomography (CT) was performed prospectively in 10 patients with histologically proven colorectal cancer using 4-detector row CT (Lightspeed Plus; GE Healthcare Technologies, Waukesha, WI). Tumor blood flow, blood volume, mean transit time, and permeability were assessed for 3 acquisition times (45, 65, and 130 seconds). Mean values for all 4 perfusion parameters for each acquisition time were compared using the paired t test. Significant differences in permeability values were noted between acquisitions of 45 seconds and 65 and 130 seconds, respectively (P=0.02, P=0.007). There was no significant difference for values of blood volume, blood flow, and mean transit time between any of the acquisition times. Scan acquisitions of 45 seconds are too short for reliable permeability measurement in the abdomen. Longer acquisition times are required.
A New Concept for Geothermal Energy Extraction: The Radiator - Enhanced Geothermal System
NASA Astrophysics Data System (ADS)
Hilpert, M.; Geiser, P.; Marsh, B. D.; Malin, P. E.; Moore, S.
2014-12-01
Enhanced Geothermal Systems (EGS) in hot dry rock frequently underperform or fail due to insufficient reservoir characterization and poorly controlled permeability stimulation. Our new EGS design is based on the concept of a cooling radiator of an internal combustion engine, which we call the Radiator EGS (RAD-EGS). Within a hot sedimentary aquifer, we propose to construct vertically extensive heat exchanger vanes, which consist of rubblized zones of high permeability and which emulate a hydrothermal system. A "crows-foot" lateral drilling pattern at multiple levels is used to form a vertical array that includes S1 and Shmax. To create the radiator, we propose to use propellant fracing. System cool-down is delayed by regional background flow and induced upward flow of the coolant which initially heats the rock. Tomographic Fracture Imaging is used to image and control the permeability field changes. Preliminary heat transfer calculations suggest that the RAD-EGS will allow for commercial electricity production for at least several tens of years.
Lee, Ka-Yeon; Song, Kyung Bin
2017-03-01
Olive flounder skin gelatin (OSG) was used as a film base material. A bilayer film of OSG and polylactic acid (PLA) was prepared using solvent casting method to enhance the film properties. Physical properties of the OSG-PLA film were increased compared with the nonaugmented OSG film. In particular, the PLA lamination decreased water vapor permeability from 2.17 to 0.92 × 10 -9 g·m/m 2 ·s·Pa, as well as of the water solubility from 16.62% to 9.27%, in the bilayer film relative to the OSG film. The oxygen permeability of the OSG-PLA bilayer film was held low by the OSG film, compensating for the high oxygen permeability of the PLA layer. Therefore, the OSG-PLA bilayer film with its enhanced physical properties and high water and oxygen barrier properties can be applied as a food packaging material. © 2017 Institute of Food Technologists®.
Improvement on Physical Properties of Pullulan Films by Novel Cross-Linking Strategy.
Chen, Chieh-Ting; Chen, Kuan-I; Chiang, Hsin-Han; Chen, Yu-Kuo; Cheng, Kuan-Chen
2017-01-01
Pullulan based films possess several advantages, including high transparency, low toxicity, good biodegradability, good mechanical properties, and low oxygen permeability, are preferable for food packaging. The application of pullulan films on food packaging, however, has inherent disadvantage of high water solubility. In this study, glutaraldehyde and glycerol were used as the cross-linking reagent and the plasticizer respectively to improve water resistance and physical properties of the pullulan films. Effects of cross-linking degree on physical properties, including water absorptions, swelling behaviors, water vapor permeability and tensile strengths of films were evaluated. FTIR results demonstrated that the pullulan films were successfully cross-linked by glutaraldehyde. The tensile strength of pullulan films could be enhanced significantly (P < 0.05) when glutaraldehyde was between 1% and 5% (w/w); nevertheless, the amount of glutaraldehyde above 20% (w/w) led to films brittleness. With the addition of glycerol as a plasticizer enhanced the extensibility of films as well as the hydrophilicity, resulting in higher water vapor permeability. © 2016 Institute of Food Technologists®.
NASA Astrophysics Data System (ADS)
Gamage, K.; Screaton, E.
2003-12-01
In this study, we used a one-dimensional model of sedimentation, initial prism loading, and fluid flow to examine the development of overpressures at the toe of the Nankai accretionary complex. A permeability-porosity relationship was established for hemipelagic sediments from laboratory measured permeabilities as an input to the model. Vertical permeabilities were measured for 10 core samples from the Ocean Drilling Program (ODP) Leg 190, Sites 1173 and 1174, from the upper and lower Shikoku Basin facies. Both sites were drilled along the Muroto Transect through the dècollement zone or its equivalent. Site 1173 is located 11 km seaward of the deformation front and it represents the undeformed incoming sediments, where as Site 1174 represents sediments within the proto-thrust zone. Although turbidite-rich sediments dominate the Nankai accretionary prism, the dècollement and underthrust sediments are primarily composed of hemipelagic muds. Using the permeability-porosity relationship, our modeling results indicate excess pore pressures that are greater than 30% of lithostatic pressure at the toe of the prism at a convergence rate of 4cm/yr. These values are slightly lower than previously inferred excess pore pressures estimated from porosity data. Additional runs were conducted to simulate a 10-m thick low permeability barrier at the dècollement where vertical fluid flow is restricted. The low permeability barrier required a permeability less than 1 x 10-19 m2 to generate excess pore pressures greater than 50% of lithostatic pressure. Modeling was further extended to test the significance of variable prism loading rates due to uncertainties in the convergence rate and affects of lateral stress above the dècollement.
Polysulfone - CNT composite membrane with enhanced water permeability
NASA Astrophysics Data System (ADS)
Hirani, Bhakti; Kar, Soumitra; Aswal, V. K.; Bindal, R. C.; Goyal, P. S.
2018-04-01
Polymeric membranes are routinely used for water purification. The performance of these conventional membranes can be improved by incorporating nanomaterials, such as metal oxide nanoparticle and carbon nanotubes (CNTs). This manuscript reports the synthesis and characterization of polysulfone (Psf) based nanocomposite membranes where multi wall carbon nanotubes (MWCNTs) and oleic acid coated Fe3O4 nanoparticles have been impregnated onto the polymeric host matrix. The performance of the membranes was evaluated by water permeability and solute rejection measurements. It was observed that the permeability of Psf membrane increases three times at 0.1% loading of MWCNT without compromise in selectivity. It was further observed that the increase in permeability is not affected upon addition of Fe3O4 nanoparticles into the membrane. In order to get a better insight into the membrane microstructure, small angle neutron scattering (SANS) studies were carried out. There is a good correlation between the water permeability and the pore sizes of the membranes as measured using SANS.
Effect of Magnetic Inclusions on the Effective Magnetostriction of Bulk Superconductors
NASA Astrophysics Data System (ADS)
Zhao, Yufeng; Pan, Baocai; Liu, Zhiguo
2018-07-01
A simple model is presented based on the Kim-Anderson model to further investigate the dependence of the effective magnetostriction of magnetic inclusion-superconducting matrix system on both the elastic and magnetic parameters including the elastic modulus, permeability, and volume fraction. The effect of the permeability on the magnetostriction is also obtained by implementing the continuity conditions of displacement and strain at the interface between the inclusion and the matrix through the magnetostriction loop. The results indicate that a stiffer inclusion can decrease the effective magnetostriction no matter whether the inclusion is magnetic or not and a larger effective magnetostriction can be obtained by choosing the matrix with a higher permeability, which gives an explanation about why the composite made from a matrix with a high permeability but a negligibly small magnetostriction yields unexpectedly low magnetostriction. Of particular interest is that in a certain range the effective magnetostriction of composites can be enhanced until it is saturated by increasing the permeability of matrix.
Naderkhani, Elenaz; Erber, Astrid; Škalko-Basnet, Nataša; Flaten, Gøril Eide
2014-02-01
The antiviral drug acyclovir (ACV) suffers from poor solubility both in lipophilic and hydrophilic environment, leading to low and highly variable bioavailability. To overcome these limitations, this study aimed at designing mucoadhesive ACV-containing liposomes to improve its permeability. Liposomes were prepared from egg phosphatidylcholine (E-PC) and E-PC/egg phosphatidylglycerol (E-PC/E-PG) and their surfaces coated with Carbopol. All liposomal formulations were fully characterized and for the first time the phospholipid vesicle-based permeation assay (PVPA) was used for testing in vitro permeability of drug from mucoadhesive liposome formulations. The negatively charged E-PC/E-PG liposomes could encapsulate more ACV than neutral E-PC liposomes. Coating with Carbopol increased the entrapment in the neutral E-PC liposomes. The incorporation of ACV into liposomes exhibited significant increase in its in vitro permeability, compared with its aqueous solution. The neutral E-PC liposomal formulations exhibited higher ACV permeability values compared with charged E-PC/E-PG formulations. Coating with Carbopol significantly enhanced the permeability from the E-PC/E-PG liposomes, as well as sonicated E-PC liposomes, which showed the highest permeability of all tested formulations. The increased permeability was according to the formulations' mucoadhesive properties. This indicates that the PVPA is suitable to distinguish between permeability of ACV from different mucoadhesive liposome formulations developed for various routes of administration. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
NASA Astrophysics Data System (ADS)
Ge, Xinmin; Fan, Yiren; Liu, Jianyu; Zhang, Li; Han, Yujiao; Xing, Donghui
2017-10-01
Permeability is an important parameter in formation evaluation since it controls the fluid transportation of porous rocks. However, it is challengeable to compute the permeability of bioclastic limestone reservoirs by conventional methods linking petrophysical and geophysical data, due to the complex pore distributions. A new method is presented to estimate the permeability based on laboratory and downhole nuclear magnetic resonance (NMR) measurements. We divide the pore space into four intervals by the inflection points between the pore radius and the transversal relaxation time. Relationships between permeability and percentages of different pore intervals are investigated to investigate influential factors on the fluid transportation. Furthermore, an empirical model, which takes into account of the pore size distributions, is presented to compute the permeability. 212 core samples in our case show that the accuracy of permeability calculation is improved from 0.542 (SDR model), 0.507 (TIM model), 0.455 (conventional porosity-permeability regressions) to 0.803. To enhance the precision of downhole application of the new model, we developed a fluid correction algorithm to construct the water spectrum of in-situ NMR data, aiming to eliminate the influence of oil on the magnetization. The result reveals that permeability is positively correlated with percentages of mega-pores and macro-pores, but negatively correlated with the percentage of micro-pores. Poor correlation is observed between permeability and the percentage of meso-pores. NMR magnetizations and T2 spectrums after the fluid correction agree well with laboratory results for samples saturated with water. Field application indicates that the improved method provides better performance than conventional models such as Schlumberger-Doll Research equation, Timur-Coates equation, and porosity-permeability regressions.
Generalized lattice Boltzmann model for flow through tight porous media with Klinkenberg's effect
NASA Astrophysics Data System (ADS)
Chen, Li; Fang, Wenzhen; Kang, Qinjun; De'Haven Hyman, Jeffrey; Viswanathan, Hari S.; Tao, Wen-Quan
2015-03-01
Gas slippage occurs when the mean free path of the gas molecules is in the order of the characteristic pore size of a porous medium. This phenomenon leads to Klinkenberg's effect where the measured permeability of a gas (apparent permeability) is higher than that of the liquid (intrinsic permeability). A generalized lattice Boltzmann model is proposed for flow through porous media that includes Klinkenberg's effect, which is based on the model of Guo et al. [Phys. Rev. E 65, 046308 (2002), 10.1103/PhysRevE.65.046308]. The second-order Beskok and Karniadakis-Civan's correlation [A. Beskok and G. Karniadakis, Microscale Thermophys. Eng. 3, 43 (1999), 10.1080/108939599199864 and F. Civan, Transp. Porous Med. 82, 375 (2010), 10.1007/s11242-009-9432-z] is adopted to calculate the apparent permeability based on intrinsic permeability and the Knudsen number. Fluid flow between two parallel plates filled with porous media is simulated to validate the model. Simulations performed in a heterogeneous porous medium with components of different porosity and permeability indicate that Klinkenberg's effect plays a significant role on fluid flow in low-permeability porous media, and it is more pronounced as the Knudsen number increases. Fluid flow in a shale matrix with and without fractures is also studied, and it is found that the fractures greatly enhance the fluid flow and Klinkenberg's effect leads to higher global permeability of the shale matrix.
Chichger, Havovi; Braza, Julie; Duong, Huetran; Harrington, Elizabeth O
2015-06-01
Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized. To assess whether SHP2 activity mediates protection against edema in the endothelium, we assessed the effect of molecular activation of SHP2 on lung endothelial barrier function in response to the edemagenic agents LPS and thrombin. Both LPS and thrombin reduced SHP2 activity, correlated with decreased focal adhesion kinase (FAK) phosphorylation (Y(397) and Y(925)) and diminished SHP2 protein-protein associations with FAK. Overexpression of constitutively active SHP2 (SHP2(D61A)) enhanced baseline endothelial monolayer resistance and completely blocked LPS- and thrombin-induced permeability in vitro and significantly blunted pulmonary edema formation induced by either endotoxin (LPS) or Pseudomonas aeruginosa exposure in vivo. Chemical inhibition of FAK decreased SHP2 protein-protein interactions with FAK concomitant with increased permeability; however, overexpression of SHP2(D61A) rescued the endothelium and maintained FAK activity and FAK-SHP2 protein interactions. Our data suggest that SHP2 activation offers the pulmonary endothelium protection against barrier permeability mediators downstream of the FAK signaling pathway. We postulate that further studies into the promotion of SHP2 activation in the pulmonary endothelium may offer a therapeutic approach for patients suffering from ALI.
Polymer-Layered Silicate Nanocomposites for Cryotank Applications
NASA Technical Reports Server (NTRS)
Miller, Sandi G.; Meador, Michael A.
2007-01-01
Previous composite cryotank designs have relied on the use of conventional composite materials to reduce microcracking and permeability. However, revolutionary advances in nanotechnology derived materials may enable the production of ultra-lightweight cryotanks with significantly enhanced durability and damage tolerance, as well as reduced propellant permeability. Layered silicate nanocomposites are especially attractive in cryogenic storage tanks based on results that have been reported for epoxy nanocomposite systems. These materials often exhibit an order of magnitude reduction in gas permeability when compared to the base resin. In addition, polymer-silicate nanocomposites have been shown to yield improved dimensional stability, strength, and toughness. The enhancement in material performance of these systems occurs without property trade-offs which are often observed in conventionally filled polymer composites. Research efforts at NASA Glenn Research Center have led to the development of epoxy-clay nanocomposites with 70% lower hydrogen permeability than the base epoxy resin. Filament wound carbon fiber reinforced tanks made with this nanocomposite had a five-fold lower helium leak rate than the corresponding tanks made without clay. The pronounced reduction observed with the tank may be due to flow induced alignment of the clay layers during processing. Additionally, the nanocomposites showed CTE reductions of up to 30%, as well as a 100% increase in toughness.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cappa, F.; Rutqvist, J.
2010-06-01
The interaction between mechanical deformation and fluid flow in fault zones gives rise to a host of coupled hydromechanical processes fundamental to fault instability, induced seismicity, and associated fluid migration. In this paper, we discuss these coupled processes in general and describe three modeling approaches that have been considered to analyze fluid flow and stress coupling in fault-instability processes. First, fault hydromechanical models were tested to investigate fault behavior using different mechanical modeling approaches, including slip interface and finite-thickness elements with isotropic or anisotropic elasto-plastic constitutive models. The results of this investigation showed that fault hydromechanical behavior can be appropriatelymore » represented with the least complex alternative, using a finite-thickness element and isotropic plasticity. We utilized this pragmatic approach coupled with a strain-permeability model to study hydromechanical effects on fault instability during deep underground injection of CO{sub 2}. We demonstrated how such a modeling approach can be applied to determine the likelihood of fault reactivation and to estimate the associated loss of CO{sub 2} from the injection zone. It is shown that shear-enhanced permeability initiated where the fault intersects the injection zone plays an important role in propagating fault instability and permeability enhancement through the overlying caprock.« less
NASA Astrophysics Data System (ADS)
Peng, Yujia; Farid Rahman, B. M.; Wang, Xuehe; Wang, Guoan
2014-05-01
Perspective magneto-dielectric materials with high permeability are potential substrates to miniaturize the patch antenna without deteriorating its performance. Besides its high permeability at high frequency, patterned Permalloy (Py) also presents tunable permeability by applying DC current. A performance enhanced miniaturized and electrically tunable patch antenna with patterned Py thin film is first presented and developed in this paper. To suppress the magnetic loss, the Py thin film layer is consisted of an array of 2 μm × 2 μm square Py patterns between the copper patch antenna and dielectric substrate. The DC current could be applied directly on Py patterns through the copper strip lines beneath the Py patterns along the length of patch antenna. The copper strip lines are specially designed with the same width of Py patterns and the thickness much less than the skin depth at the operating frequency, which can reduce their deteriorating effects to the performance of antenna. The structure of the antenna is presented and simulated with high frequency structure simulator. The results show that compared with non-magnetic antenna, the performance of Py thin film based antenna is improved with 50% bandwidth increase from 4 MHz to 8 MHz and 1.2 dB gain enhancement from 1.16 dB to 2.36 dB. The resonant frequency of the antenna could be continuously tuned from 937 MHz to 911 MHz with the permeability of Py thin film changing from 1750 to 1 900 by applying the DC current.
Li, Fang; Wang, Yueyun; Yu, Lan; Cao, Shengbo; Wang, Ke; Yuan, Jiaolong; Wang, Chong; Wang, Kunlun; Cui, Min; Fu, Zhen F
2015-05-01
Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate that JEV gains entry into the CNS prior to BBB disruption. Furthermore, it is not JEV infection per se, but the inflammatory cytokines/chemokines induced by JEV infection that inhibit the expression of TJ proteins and ultimately result in the enhancement of BBB permeability. Neutralization of gamma interferon (IFN-γ) ameliorated the enhancement of BBB permeability in JEV-infected mice, suggesting that IFN-γ could be a potential therapeutic target. This study would lead to identification of potential therapeutic avenues for the treatment of JEV infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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.
Van Stappen, Jeroen F; Meftah, Redouane; Boone, Marijn A; Bultreys, Tom; De Kock, Tim; Blykers, Benjamin K; Senger, Kim; Olaussen, Snorre; Cnudde, Veerle
2018-04-17
On Svalbard, Arctic Norway, an unconventional siliciclastic reservoir, relying on (micro)fractures for enhanced fluid flow in a low-permeable system, is investigated as a potential CO 2 sequestration site. The fractures' properties at depth are, however, poorly understood. High resolution X-ray computed tomography (micro-CT) imaging allows one to visualize such geomaterials at reservoir conditions. We investigated reservoir samples from the De Geerdalen Formation on Svalbard to understand the influence of fracture closure on the reservoir fluid flow behavior. Small rock plugs were brought to reservoir conditions, while permeability was measured through them during micro-CT imaging. Local fracture apertures were quantified down to a few micrometers wide. The permeability measurements were complemented with fracture permeability simulations based on the obtained micro-CT images. The relationship between fracture permeability and the imposed confining pressure was determined and linked to the fracture apertures. The investigated fractures closed due to the increased confining pressure, with apertures reducing to approximately 40% of their original size as the confining pressure increased from 1 to 10 MPa. This coincides with a permeability drop of more than 90%. Despite their closure, fluid flow is still controlled by the fractures at pressure conditions similar to those at the proposed storage depth of 800-1000 m.
NASA Astrophysics Data System (ADS)
Carey, J. W.; Mori, H.; Porter, M. L.; Lewis, K. C.; Kelkar, S.
2013-12-01
Potential leakage from wells is an important issue in the protection of groundwater resources, CO2 sequestration, and hydraulic fracturing. The first defense in all of these applications is a properly constructed well with adequate Portland cement that effectively isolates the subsurface. The chief threat for such wells is mechanical disruption of the cement, cement/steel, or cement/caprock interfaces. This can occur through wellbore operations that pressurize/depressurize the steel tubing or create temperature transients (e.g., injection, production, hydraulic fracturing, and mechanical testing) as well as reservoir-scale stresses (e.g., filling or depletion of the reservoir) and tectonic stresses (e.g., the mobility of salt). However, there is relatively limited information available on the hydrologic consequences of such processes. Toward this end, we discuss recent experiments and computational models of coupled geomechanical and hydrologic processes in wellbore systems. Triaxial coreflood experiments with tomography were conducted on synthetic wellbore systems including cement-steel, rock-cement and rock-cement-steel composites. The aim of the experiments was to induce stresses through application of axial loads in order to create defects within the cement or at the cement/steel or cement/rock interface. High injection fluid pressures (supercritical CO2 × brine) were applied to the base of the initially impermeable composites. Mechanical failure resulted in creation of permeability, which was measured as a function of time (allowing for the possibility of Portland cement to deform and modify permeability). In addition, fracture patterns were characterized using x-ray tomography. We used the computer code FEHM to study coupled hydrologic and mechanical processes in the near-wellbore environment. The wellbore model was developed as a wedge within a radially symmetric 3D volume. The grid elements consist of the steel casing, the casing-cement interface, the cement, the cement-rock interface, caprock, and reservoir rock. We used a model that is 1 m in radius, and extends 5 m along the wellbore. The model consisted of a lower storage aquifer, a caprock and an upper aquifer that received leaking fluids. We coupled flow and geomechanics using a shear-failure model that represents shear-induced damage and is similar to a Mohr-Coulomb slip mechanism. In this model, damage occurs for any excess shear stress with permeability enhancement a function of stress with a maximum magnitude set by the user. Stresses were induced by application of an elevated constant pressure within the injection reservoir representing a far-field injection process. The initial permeability of the cement was 1 mD and stress-enhanced permeability was limited to an increase by a factor of 10-100. The simulations show that shear-failure modes lead to enhanced permeability of the wellbore system. Continuing work will examine sensitivity of the results to mechanical properties and initial permeability distributions, the impact of relative permeability models, and the development of permeability-stress models including an aperture-opening tensile-failure model.
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.
Role of S waves and Love waves in coseismic permeability enhancement
NASA Astrophysics Data System (ADS)
Wang, Chi-yuen; Chia, Yeeping; Wang, Pei-ling; Dreger, Douglas
2009-05-01
The 2008 M7.9 Wenchuan earthquake in Sichuan, China, caused water level to oscillate and undergo sustained changes in Taiwan, ˜2000 km away from the epicenter. Here we use the responses in three wells recorded at high sampling rate (1 Hz) and the broadband seismograms from a nearby station to document, for the first time, that the major water-level responses associated with Rayleigh waves were preceded by small oscillations that occurred concurrently with S waves and Love waves. We also show that the groundwater flow associated with these small oscillations may be strong enough to remove blockades from sediment pores to enhance aquifer permeability and to facilitate the later major responses.
Chemically enhanced in situ recovery
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sale, T.; Pitts, M.; Wyatt, K.
1996-08-01
Chemically enhanced recovery is a promising alternative to current technologies for management of subsurface releases of organic liquids. Through the inclusion of surfactants, solvents, polymers, and/or alkaline agents to a waterflood, the transport of targeted organic compounds can be increased and rates of recovery enhanced. By far, the vast majority of work done in the field of chemically enhanced recovery has been at a laboratory scale. The following text focuses on chemically enhanced recovery from a field application perspective with emphasis given to chlorinated solvents in a low permeability setting. While chlorinated solvents are emphasized, issues discussed are also relevantmore » to organic liquids less dense than water such as petroleum products. Topics reviewed include: (1) Description of technology; (2) General technology considerations; (3) Low permeability media considerations; (4) Cost and reliability considerations; (5) Commercial availability; and (6) Case histories. Through this paper an appreciation is developed of both the potential and limitations of chemically enhanced recovery. Excluded from the scope of this paper is the in situ destruction of organic compounds through processes such as chemical or biological oxidation, chemically enhanced recovery of inorganic compounds, and ex situ soil treatment processes. 11 refs., 2 figs., 1 tab.« less
Abate, Salvatore; Giorgianni, Gianfranco; Gentiluomo, Serena; Centi, Gabriele; Perathoner, Siglinda
2015-11-01
Palladium ultrathin films (around 2 μm) with different surface nanostructures are characterized by TEM, SEM, AFM, and temperature programmed reduction (TPR), and evaluated in terms of H2 permeability and H2-N2 separation. A change in the characteristics of Pd seeds by controlled oxidation-reduction treatments produces films with the same thickness, but different surface and bulk nanostructure. In particular, the films have finer and more homogeneous Pd grains, which results in lower surface roughness. Although all samples show high permeo-selectivity to H2 , the samples with finer grains exhibit enhanced permeance and lower activation energy for H2 transport. The analysis of the data suggests that grain boundaries between the Pd grains at the surface favor H2 transfer from surface to subsurface. Thus, the surface nanostructure plays a relevant role in enhancing the transport of H2 over the Pd ultrathin film, which is an important aspect to develop improved membranes that function at low temperatures and toward new integrated process architectures in H2 and syngas production with enhanced sustainability. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Huang, Wen; Chen, Lei; Zhang, Bei; Park, Minseon; Toborek, Michal
2014-01-01
The strategies to protect against the disrupted blood–brain barrier (BBB) in HIV-1 infection are not well developed. Therefore, we investigated the potential of peroxisome proliferator-activated receptor (PPAR) agonists to prevent enhanced BBB permeability induced by HIV-1-specific protein Tat. Exposure to Tat via the internal carotid artery (ICA) disrupted permeability across the BBB; however, this effect was attenuated in mice treated with fenofibrate (PPARα agonist) or rosiglitazone (PPARγ agonist). In contrast, exposure to GW9662 (PPARγ antagonist) exacerbated Tat-induced disruption of the BBB integrity. Increased BBB permeability was associated with decreased tight junction (TJ) protein expression and activation of ERK1/2 and Akt in brain microvessels; these effects were attenuated by cotreatment with fenofibrate but not with rosiglitazone. Importantly, both PPAR agonists also protected against Tat-induced astrogliosis and neuronal loss. Because disruption of TJ integrity has been linked to matrix metalloproteinase (MMP) activity, we also evaluated Tat-induced effects in MMP-9-deficient mice. Tat-induced cerebrovascular toxicity, astrogliosis, and neuronal loss were less pronounced in MMP-9-deficient mice as compared with wild-type controls and were further attenuated by PPAR agonists. These results indicate that enhancing PPAR activity combined with targeting MMPs may provide effective therapeutic strategies in brain infection by HIV-1. PMID:24424383
Matrix-type transdermal films to enhance simvastatin ex vivo skin permeability.
El-Say, Khalid M; Ahmed, Osama A A; Aljaeid, Bader M; Zidan, Ahmed S
2017-06-01
This study aimed at employing Plackett-Burman design in screening formulation variables that affect quality of matrix-type simvastatin (SMV) transdermal film. To achieve this goal, 12 formulations were prepared by casting method. The investigated variables were Eudragit RL percentage, polymer mixture percentage, plasticizer type, plasticizer percentage, enhancer type, enhancer percentage and dichloromethane fraction in organic phase. The films were evaluated for physicochemical properties and ex vivo SMV permeation. SMV initial, delayed flux, diffusivity and permeability coefficient were calculated on the delayed flux phase with constraint to minimize the initial flux and approaching steady-state flux. The obtained results revealed flat films with homogeneous distribution of SMV within the films. Thickness values changed from 65 to 180 μm by changing the factors' combinations. Most of the permeation profiles showed sustained release feature with fast permeation phase followed by slow phase. Analysis of variance (ANOVA) showed significant effects (p < 0.05) of the investigated variables on the responses with Prob > F values of 0.0147, 0.0814, 0.0063 and 0.0142 for the initial and delayed fluxes, permeability coefficients and diffusivities, respectively. The findings of screening study showed the importance of the significant variables to be scaled up for full optimization study as a promising alternative drug delivery system.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahmad, N.; Keith, B.D.; Thompson, T.A.
Shoal facies of the Salem Limestone in south-central Indiana are composed of (1) bryozoan- and echinoderm-rich (85-95%) grainstones, and (3) foraminiferal-echinodermal grainstones. Microfacies and bedform analyses indicate that deposition took place under tidal conditions where sporadic storm events mobilized the entire sand body. Strong, primarily unidirectional currents, abundant sediment supply, and rapid burial resulted in thick, massive deposits in the Salem shoal. In this hydraulic regime, shape and specific gravity determined the distribution of echinoderm grains relative to heavier bryozoan grains. The relative amount of echinoderms controlled the development of early syntaxial rim cement, which preserved porosity during early compaction.more » A significant amount of calcium carbonate ({approximately}58%) filled the micropores within the echinoderm grains before the intergranular cement could form. Areas such as toes of avalanche forests, where intermediate amounts of echinoderms are mixed with other grains, have greater porosity and permeability. Numerous stylolites also occur throughout the Salem grainstones. Variations in microfacies composition and bedforms are grouped into architectural packages that compartmentalize the porosity and permeability and form micro-to scale macroscale heterogeneities. The basal channel architectural package studied exhibits porosity-permeability compartments orthogonal to the overlying channel-fill sandwave package. In an analogous petroleum reservoir this can result in poor reservoir performance during primary and enhanced recovery leaving behind significant amounts of unrecovered mobile oil. Higher porosity and permeability at the base of a package due to the presence of toesets of a certain grain composition can result in poor sweep efficiency for enhanced recovery.« less
Ultrasound-enhanced delivery of antibiotics and anti-inflammatory drugs into the eye.
Nabili, Marjan; Patel, Hetal; Mahesh, Sankaranarayana P; Liu, Ji; Geist, Craig; Zderic, Vesna
2013-04-01
Delivery of sufficient amounts of therapeutic drugs into the eye is often a challenging task. In this study, ultrasound application (frequencies of 400 KHz to 1 MHz, intensities of 0.3-1.0 W/cm(2) and exposure duration of 5 min) was investigated to overcome the barrier properties of cornea, which is a typical route for topical administration of ophthalmic drugs. Permeability of ophthalmic drugs, tobramycin and dexamethasone and sodium fluorescein, a drug-mimicking compound, was studied in ultrasound- and sham-treated rabbit corneas in vitro using a standard diffusion cell setup. Light microscopy observations were used to determine ultrasound-induced structural changes in the cornea. For tobramycin, an increase in permeability for ultrasound- and sham-treated corneas was not statistically significant. Increase of 46%-126% and 32%-109% in corneal permeability was observed for sodium fluorescein and dexamethasone, respectively, with statistical significance (p < 0.05) achieved at all treatment parameter combinations (compared with sham treatments) except for 1-MHz ultrasound applications for dexamethasone experiments. This permeability increase was highest at 400 kHz and appeared to be higher at higher intensities applied. Histologic analysis showed structural changes that were limited to epithelial layers of cornea. In summary, ultrasound application provided enhancement of drug delivery, increasing the permeability of the cornea for the anti-inflammatory ocular drug dexamethasone. Future investigations are needed to determine the effectiveness and safety of this application in in vivo long-term survival studies. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Lee, Chung Soo; Kim, Yun Jeong; Ko, Hyun Hee; Han, Eun Sook
2005-07-15
The promoting effect of ethanol against the cytotoxicity of hydrogen peroxide (H2O2) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with H2O2 resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. In PC12 cells and dopaminergic neuroblastoma SH-SY5Y cells, the promoting effect of ethanol on the H2O2-induced cell death was increased with exposure time. Ethanol promoted the nuclear damage, change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to H2O2 in PC12 cells. Catalase, carboxy-PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the H2O2 and ethanol-induced mitochondrial dysfunction and cell injury. The results show that the ethanol treatment promotes the cytotoxicity of H2O2 against PC12 cells. Ethanol may enhance the H2O2-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of ROS and depletion of GSH. The findings suggest that ethanol as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by oxidants.
NASA Astrophysics Data System (ADS)
Fan, Jingjing; Feng, Ruimin; Wang, Jin; Wang, Yanbin
2017-07-01
Geological sequestration of CO2 in coal seams is of significant interest to both academia and industry. A thorough laboratory investigation of mechanical and flow behaviors is crucial for understanding the complex response of coalbeds to CO2 injection-enhanced coalbed methane recovery (CO2-ECBM) operation. In this work, systematic experiments were carried out on cylindrical coal core specimens under different uniform confining stresses. The coal deformation caused by variations in effective stress as well as the sorption-induced matrix swelling/shrinkage was monitored. The competitive gas sorption characteristics and permeability evolution during the process of methane displacement by CO2 were also investigated. The measured volumetric strain results indicate that sorption-induced strain is the dominant factor in the coal deformation. The relationship between the volumetric strain and the adsorbed gas volume has been revealed to be a linear function. Experimental results obtained under different stress conditions suggest that higher confining stress suppresses the increase in both volumetric strain and the adsorbed gas volume. Furthermore, both methane displacement and CO2 injection are reduced when applying higher confining stresses. In addition, the permeability enhancement is heavily suppressed at higher confining stress. At a certain confining stress, a characteristic "U-shaped" trend of permeability is presented as a function of decreasing pore pressure. This study contributes to the understanding of coal deformation and its impact on permeability evolution under uniformly stressed condition, which has practical significance for CO2 sequestration and CO2-ECBM operation in the Qinshui basin.
STANDARD MEASUREMENT PROTOCOLS - FLORIDA RADON RESEARCH PROGRAM
The manual, in support of the Florida Radon Research Program, contains standard protocols for key measurements where data quality is vital to the program. t contains two sections. he first section, soil measurements, contains field sampling protocols for soil gas permeability and...
Beig, Avital; Agbaria, Riad; Dahan, Arik
2013-01-01
The purpose of this study was to investigate the impact of oral cyclodextrin-based formulation on both the apparent solubility and intestinal permeability of lipophilic drugs. The apparent solubility of the lipophilic drug dexamethasone was measured in the presence of various HPβCD levels. The drug’s permeability was measured in the absence vs. presence of HPβCD in the rat intestinal perfusion model, and across Caco-2 cell monolayers. The role of the unstirred water layer (UWL) in dexamethasone’s absorption was studied, and a simplified mass-transport analysis was developed to describe the solubility-permeability interplay. The PAMPA permeability of dexamethasone was measured in the presence of various HPβCD levels, and the correlation with the theoretical predictions was evaluated. While the solubility of dexamethasone was greatly enhanced by the presence of HPβCD (K1∶1 = 2311 M−1), all experimental models showed that the drug’s permeability was significantly reduced following the cyclodextrin complexation. The UWL was found to have no impact on the absorption of dexamethasone. A mass transport analysis was employed to describe the solubility-permeability interplay. The model enabled excellent quantitative prediction of dexamethasone’s permeability as a function of the HPβCD level. This work demonstrates that when using cyclodextrins in solubility-enabling formulations, a tradeoff exists between solubility increase and permeability decrease that must not be overlooked. This tradeoff was found to be independent of the unstirred water layer. The transport model presented here can aid in striking the appropriate solubility-permeability balance in order to achieve optimal overall absorption. PMID:23874557
Code of Federal Regulations, 2014 CFR
2014-04-01
... water supply. A system, including facilities for collection, treatment, storage and distribution, that... extraction of gaseous hydrocarbons from low permeability geologic formations utilizing enhanced drilling...
Code of Federal Regulations, 2013 CFR
2013-04-01
... water supply. A system, including facilities for collection, treatment, storage and distribution, that... extraction of gaseous hydrocarbons from low permeability geologic formations utilizing enhanced drilling...
Code of Federal Regulations, 2012 CFR
2012-04-01
... water supply. A system, including facilities for collection, treatment, storage and distribution, that... extraction of gaseous hydrocarbons from low permeability geologic formations utilizing enhanced drilling...
Shah, Devang; Paruchury, Sundeep; Matta, Muralikrishna; Chowan, Gajendra; Subramanian, Murali; Saxena, Ajay; Soars, Matthew G; Herbst, John; Haskell, Roy; Marathe, Punit; Mandlekar, Sandhya
2014-01-01
The study presented here identified and utilized a panel of solubility enhancing excipients to enable the generation of flux data in the Human colon carcinoma (Caco-2) system for compounds with poor solubility. Solubility enhancing excipients Dimethyl acetamide (DMA) 1 % v/v, polyethylene glycol (PEG) 400 1% v/v, povidone 1% w/v, poloxamer 188 2.5% w/v and bovine serum albumin (BSA) 4% w/v did not compromise Caco-2 monolayer integrity as assessed by trans-epithelial resistance measurement (TEER) and Lucifer yellow (LY) permeation. Further, these excipients did not affect P-glycoprotein (P-gp) mediated bidirectional transport of digoxin, permeabilities of high (propranolol) or low permeability (atenolol) compounds, and were found to be inert to Breast cancer resistant protein (BCRP) mediated transport of cladribine. This approach was validated further using poorly soluble tool compounds, atazanavir (poloxamer 188 2.5% w/v) and cyclosporine A (BSA 4% w/v) and also applied to new chemical entity (NCE) BMS-A in BSA 4% w/v, for which Caco-2 data could not be generated using the traditional methodology due to poor solubility (<1 µM) in conventional Hanks balanced salt solution (HBSS). Poloxamer 188 2.5% w/v increased solubility of atazanavir by >8 fold whereas BSA 4% w/v increased the solubility of cyclosporine A and BMS-A by >2-4 fold thereby enabling permeability as well as efflux liability estimation in the Caco-2 model with reasonable recovery values. To conclude, addition of excipients such as poloxamer 188 2.5% w/v and BSA 4% w/v to HBSS leads to a significant improvement in the solubility of the poorly soluble compounds resulting in enhanced recoveries without modulating transporter-mediated efflux, expanding the applicability of Caco-2 assays to poorly soluble compounds.
On the influence of surfactant on the coarsening of aqueous foams.
Briceño-Ahumada, Zenaida; Langevin, Dominique
2017-06-01
We review the coarsening process of foams made with various surfactants and gases, focusing on physico-chemical aspects. Several parameters strongly affect coarsening: foam liquid fraction and foam film permeability, this permeability depending on the surfactant used. Both parameters may evolve with time: the liquid fraction, due to gravity drainage, and the film permeability, due to the decrease of capillary pressure during bubble growth, and to the subsequent increase in film thickness. Bubble coalescence may enhance the bubble's growth rate, in which case the bubble polydispersity increases. The differences found between the experiments reported in the literature and between experiments and theories are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.
Pyroelectricity as a possible mechanism for cell membrane permeabilization.
García-Sánchez, Tomás; Muscat, Adeline; Leray, Isabelle; Mir, Lluis M
2018-02-01
The effects of pyroelectricity on cell membrane permeability had never been explored. Pyroelectricity consists in the generation of an electric field in the surface of some materials when a change in temperature is produced. In the present study, tourmaline microparticles, which are known to display pyroelectrical properties, were subjected to different changes in temperature upon exposure to cells in order to induce an electric field at their surface. Then, the changes in the permeability of the cell membrane to a cytotoxic agent (bleomycin) were assessed by a cloning efficacy test. An increase in the permeability of the cell membrane was only detected when tourmaline was subjected to a change in temperature. This suggests that the apparition of an induced pyroelectrical electric field on the material could actually be involved in the observed enhancement of the cell membrane permeability as a result of cell electropermeabilization. Copyright © 2017 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Ramadan, Bimastyaji Surya; Effendi, Agus Jatnika; Helmy, Qomarudin
2018-02-01
Traditional oil mining activities always ignores environmental regulation which may cause contamination in soil and environment. Crude oil contamination in low-permeability soil complicates recovery process because it requires substantial energy for excavating and crushing the soil. Electrokinetic technology can be used as an alternative technology to treat contaminated soil and improve bioremediation process (biostimulation) through transfer of ions and nutrient that support microorganism growth. This study was conducted using a combination of electrokinetic and bioremediation processes. Result shows that the application of electrokinetic and bioremediation in low permeability soils can provide hydrocarbon removal efficiency up to 46,3% in 7 days operation. The highest amount of microorganism can be found in 3-days operation, which is 2x108 CFU/ml using surfactant as flushing fluid for solubilizing hydrocarbon molecules. Enhancing bioremediation using electrokinetic process is very potential to recover oil contaminated low permeability soil in the future.
Tian, Yuan; Jiang, Yanhong; Li, Jingxu; Wang, Dongyuan; Zhao, Hui; Li, Zigang
2017-11-02
Stapled peptides have emerged as a new class of targeting molecules with high binding affinity and specificity for intracellular undruggable targets. Their ability to penetrate cell membranes is exceptionally intriguing but remains elusively and controversially discussed. To understand the effect of stapling architectures on their physiochemical properties and to aid in promoting their cell permeability, we report herein a comparative study on the physiochemical properties and cell permeability of stapled α-helical peptides with different types of crosslinks. We highlight the decisive impact of the intrinsic properties of the crosslinks on cell permeability rather than the helical contents of the peptides in model amphipathic sequences targeting estrogen receptor-coactivator interaction. We envision this finding to shed further light on the chemical optimization of stapled α-helical peptides or macrocyclic cell-penetrating peptides for enhanced cell penetration. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav; Boretius, Susann
2016-01-01
Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.
Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar
2015-09-01
The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs.
Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar
2015-01-01
Purpose: The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. Methods: The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. Results: In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. Conclusion: It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs. PMID:26504763
Fan, Xinfei; Zhao, Huimin; Liu, Yanming; Quan, Xie; Yu, Hongtao; Chen, Shuo
2015-02-17
Membrane filtration provides effective solutions for removing contaminants, but achieving high permeability, good selectivity, and antifouling ability remains a great challenge for existing membrane filtration technologies. In this work, membrane filtration coupled with electrochemistry has been developed to enhance the filtration performance of a CNTs/Al2O3 membrane. The as-prepared CNTs/Al2O3 membrane, obtained by coating interconnected CNTs on an Al2O3 substrate, presented good pore-size tunability, mechanical stability, and electroconductivity. For the removal of a target (silica spheres as a probe) with a size comparable to the membrane pore size, the removal efficiency and flux at +1.5 V were 1.1 and 1.5 times higher, respectively, than those without electrochemical assistance. Moreover, the membrane also exhibited a greatly enhanced removal efficiency for contaminants smaller than the membrane pores, providing enhancements of 4 orders of magnitude and a factor of 5.7 for latex particles and phenol, respectively. These results indicated that both the permeability and the selectivity of CNTs/Al2O3 membranes can be significantly improved by electrochemical assistance, which was further confirmed by the removal of natural organic matter (NOM). The permeate flux and NOM removal efficiency at +1.5 V were about 1.6 and 3.0 times higher, respectively, than those without electrochemical assistance. In addition, the lost flux of the fouled membrane was almost completely recovered by an electrochemically assisted backwashing process.
Kim, Jean; Schlesinger, Erica B; Desai, Tejal A
2015-01-01
Effective drug delivery to the eye is an ongoing challenge due to poor patient compliance coupled with numerous physiological barriers. Eye drops for the front of the eye and ocular injections for the back of the eye are the most prevalent delivery methods, both of which require relatively frequent administration and are burdensome to the patient. Novel drug delivery techniques stand to drastically improve safety, efficacy and patient compliance for ocular therapeutics. Remarkable advances in nanofabrication technologies make the application of nanostructured materials to ocular drug delivery possible. This article focuses on the use of nanostructured materials with nanoporosity or nanotopography for ocular delivery. Specifically, we discuss nanotopography for enhanced bioadhesion and permeation and nanoporous materials for controlled release drug delivery. As examples, application of polymeric nanostructures for greater transepithelial permeability, nanostructured microparticles for enhanced preocular retention time and nanoporous membranes for tuning drug release profile are covered. PMID:26652282
Enhanced bioremediation of BTEX using immobilized nutrients: Field demonstration and monitoring
DOE Office of Scientific and Technical Information (OSTI.GOV)
Borden, R.C.; Goin, R.T.; Kao, C.M.
1996-12-01
A permeable barrier system was developed for controlling the migration of dissolved contaminant plumes in ground water. The barrier system consisted of a line of closely spaced wells installed perpendicular to the contaminant plume. Each well contained concrete briquets that released oxygen and nitrate at a controlled rate, enhancing the aerobic biodegradation of dissolved hydrocarbons in the downgradient aquifer. A full scale permeable barrier system was constructed at a gasoline-spill site near Leland, NC. Initially, increased dissolved oxygen and decreased benzene, toluene, ethylbenzene, and xylene isomer (BTEX) concentrations in the downgradient aquifer indicated that oxygen released from the remediation wellsmore » was enhancing biodegradation. Field tracer tests and soil analyses performed at the conclusion of the project indicated that the aquifer in the vicinity of the remediation wells was being clogged by precipitation from iron minerals.« less
NASA Astrophysics Data System (ADS)
Chang, S. L.; Lottes, S. A.; Berry, G. F.
Argonne National Laboratory is investigating the non-reacting jet-gas mixing patterns in a magnetohydrodynamics (MHD) second stage combustor by using a three-dimensional single-phase hydrodynamics computer program. The computer simulation is intended to enhance the understanding of flow and mixing patterns in the combustor, which in turn may improve downstream MHD channel performance. The code is used to examine the three-dimensional effects of the side walls and the distributed jet flows on the non-reacting jet-gas mixing patterns. The code solves the conservation equations of mass, momentum, and energy, and a transport equation of a turbulence parameter and allows permeable surfaces to be specified for any computational cell.
Oral microemulsions of paclitaxel: in situ and pharmacokinetic studies.
Nornoo, Adwoa O; Zheng, Haian; Lopes, Luciana B; Johnson-Restrepo, Boris; Kannan, Kurunthachalam; Reed, Rachel
2009-02-01
The overall goal of this study was to develop cremophor-free oral microemulsions of paclitaxel (PAC) to enhance its permeability and oral absorption. The mechanism of this enhancement, as well as characteristics of the microemulsions relevant to the increase in permeability and absorption of the low solubility, low permeability PAC was investigated. Phase diagrams were used to determine the macroscopic phase behavior of the microemulsions and to compare the efficiency of different surfactant-oil mixtures to incorporate water. The microemulsion region on the phase diagrams utilizing surfactant-myvacet oil combinations was in decreasing order: lecithin: butanol: myvacet oil (LBM, 48.5%)>centromix CPS: 1-butanol: myvacet oil (CPS, 45.15%)>capmul MCM: polysorbate 80: myvacet oil (CPM, 27.6%)>capryol 90: polysorbate 80: myvacet oil (CP-P80, 23.9%)>capmul: myvacet oil (CM, 20%). Oil-in-water (o/w) microemulsions had larger droplet sizes (687-1010 nm) than the water-in-oil (w/o) microemulsions (272-363 nm) when measured using a Zetasizer nano series particle size analyzer. Utilizing nuclear magnetic resonance spectroscopy (NMR), the self-diffusion coefficient (D) of PAC in CM, LBM and CPM containing 10% of deuterium oxide (D(2)O) was 2.24x10(-11), 1.97x10(-11) and 0.51x10(-11) m(2)/s, respectively. These values indicate the faster molecular mobility of PAC in the two w/o microemulsions (CM and LBM) than the o/w microemulsion--CPM. The in situ permeability of PAC through male CD-IGS rat intestine was 3- and 11-fold higher from LBM and CM, respectively, than that from the control clinical formulation, Taxol (CE, cremophor: ethanol) in a single pass perfusion study. PAC permeability was significantly increased in the presence of the pgp/CYP3A4 inhibitor cyclosporine A (CsA). This enhancement may be attributed to the pgp inhibitory effect of the surfactants, oil and/or the membrane perturbation effect of the surfactants. The oral disposition of PAC in CM, LBM and CPM compared to CE was studied in male CD-IGS rats after a single oral dose (20 mg/kg). The area-under-the-curve of PAC in CM was significantly larger than LBM, CPM and CE. Oral microemulsions of PAC were developed that increased both the permeability and AUC of PAC as compared to CE.
Jia, Lee; Wong, Hong
2001-01-01
The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (Papp; cm sec−1) of CapNO across the endothelial monolayers was 6.0×10−5, higher than that of Cap (3.13×10−5), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The Papp of CapNO and Cap across Caco-2 cells were 3.15×10−5 and 1.53×10−5, respectively. The low Papp of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H2-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects. PMID:11739246
Jia, L; Wong, H
2001-12-01
1. The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. 2. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (P(app); cm sec(-1)) of CapNO across the endothelial monolayers was 6.0 x 10(-5), higher than that of Cap (3.13 x 10(-5)), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The P(app) of CapNO and Cap across Caco-2 cells were 3.15 x 10(-5) and 1.53 x 10(-5), respectively. The low P(app) of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. 3. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. 4. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H(2)-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. 5. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects.
Bank, Norman; Yarger, William E.; Aynedjian, Hagop S.
1971-01-01
Constriction of the renal vein has been shown to inhibit net sodium and water reabsorption by the rat proximal tubule. The mechanism is unknown but might be the result of inhibition of the active sodium pump induced by changes in the interstitial fluid compartment of the kidney, or to enhanced passive backflux of sodium and water into the cell or directly into the tubular lumen. Since passive movement of solutes across epithelial membranes is determined in part by the permeability characteristics of the epithelium, an increase in the permeability of the proximal tubule during venous constriction would suggest that enhanced passive flux is involved in the inhibition of reabsorption. In the present experiments, isolated segments of rat proximal convoluted tubules were microperfused in vivo with saline while the animals were receiving 14C-labeled sucrose intravenously. In normal control animals, no sucrose was detected in the majority of the collected tubular perfusates. In rats with renal vein constriction (RVC), however, sucrose consistently appeared in the tubular perfusates. The rate of inflow of sucrose correlated with the length of the perfused segment, estimated by fractional water reabsorption. In another group of animals with renal vein constriction, inulin-14C was given intravenously and the proximal tubules similarly microperfused. Inulin did not appear in the majority of collected perfusates in these animals. These observations indicate that a physiological alteration in the permeability of the proximal tubule occurs during RVC. Such an increase in permeability is consistent with the view that enhanced passive extracellular back-flux plays a role in the reduction of net sodium and water reabsorption in this experimental condition. PMID:5540167
Rich, Kyle T; Hoerig, Cameron L; Rao, Marepalli B; Mast, T Douglas
2014-11-28
Enhanced skin permeability is known to be achieved during sonophoresis due to ultrasound-induced cavitation. However, the mechanistic role of cavitation during sonophoresis has been extensively investigated only for low-frequency (LFS, <100 kHz) applications. Here, mechanisms of permeability-enhancing stable and inertial cavitation were investigated by passively monitoring subharmonic and broadband emissions arising from cavitation isolated within or external to porcine skin in vitro during intermediate- (IFS, 100-700 kHz) and high-frequency sonophoresis (HFS, >1 MHz). The electrical resistance of skin, a surrogate measure of the permeability of skin to a variety of compounds, was measured to quantify the reduction and subsequent recovery of the skin barrier during and after exposure to pulsed (1 second pulse, 20% duty cycle) 0.41 and 2.0 MHz ultrasound over a range of acoustic powers (0-21.7 W) for 30 min. During IFS, significant skin resistance reductions and acoustic emissions from cavitation were measured exclusively when cavitation was isolated outside of the skin. Time-dependent skin resistance reductions measured during IFS correlated significantly with subharmonic and broadband emission levels. During HFS, significant skin resistance reductions were accompanied by significant acoustic emissions from cavitation measured during trials that isolated cavitation activity either outside of skin or within skin. Time-dependent skin resistance reductions measured during HFS correlated significantly greater with subharmonic than with broadband emission levels. The reduction of the skin barrier due to sonophoresis was reversible in all trials; however, effects incurred during IFS recovered more slowly and persisted over a longer period of time than HFS. These results quantitatively demonstrate the significance of cavitation during sonophoresis and suggest that the mechanisms and post-treatment longevity of permeability enhancement due to IFS and HFS treatments are different. Copyright © 2014 Elsevier B.V. All rights reserved.
Fang, Xiaofeng; Li, Jiansheng; Li, Xin; Pan, Shunlong; Sun, Xiuyun; Shen, Jinyou; Han, Weiqing; Wang, Lianjun; Van der Bruggen, Bart
2017-11-01
In this work, an iron-tannin-framework (ITF) complex was introduced to a poly (ether sulfone) (PES) casting solution as a hydrophilic additive to fabricate ITF/PES ultrafiltration (UF) membranes via non-solvent-induced phase separation (NIPS). The structure and performance of the PES membranes with ITF concentrations ranging from 0 to 0.9wt.% were systematically investigated by scanning electron microscopy, water contact angle, permeability, protein rejection and fouling resistance measurements. The results indicate that the pore structure and surface properties of PES UF membranes can be regulated by incorporating the ITF complex. Compared with classical PES membranes, ITF/PES membranes were found to have an increased hydrophilicity and porosity and reduced surface pore size. Importantly, a simultaneous enhancement of permeability and separation performance was observed for the blend membranes, which indicates that the introduction of the ITF complex can break through the trade-off between permeability and selectivity of UF membranes.When the ITF content was 0.3wt.%, the permeability reached a maximum of 319.4(L/m 2 h) at 0.1MPa, which is 1.6 times higher than that of the classical PES membrane. Furthermore, the BSA rejection increased from 25.9% for the PES membrane to 95.9% for the enhanced membrane. In addition, the same membrane showed an improved fouling resistance (higher flux recovery and lower adhesion force) and stable hydrophilicity (unchanged after incubation in deionized water for 30days). The simple, green and cost-effective preparation process and the outstanding filtration performance highlight the potential of ITF/PES membranes for practical applications. Copyright © 2017 Elsevier Inc. All rights reserved.
Lévesque, Jean-François; Bleasby, Kelly; Chefson, Amandine; Chen, Austin; Dubé, Daniel; Ducharme, Yves; Fournier, Pierre-André; Gagné, Sébastien; Gallant, Michel; Grimm, Erich; Hafey, Michael; Han, Yongxin; Houle, Robert; Lacombe, Patrick; Laliberté, Sébastien; MacDonald, Dwight; Mackay, Bruce; Papp, Robert; Tschirret-Guth, Richard
2011-09-15
An oral bioavailability issue encountered during the course of lead optimization in the renin program is described herein. The low F(po) of pyridone analogs was shown to be caused by a combination of poor passive permeability and gut efflux transport. Substitution of pyridone ring for a more lipophilic moiety (logD>1.7) had minimal effect on rMdr1a transport but led to increased passive permeability (P(app)>10 × 10(-6) cm/s), which contributed to overwhelm gut transporters and increase rat F(po). LogD and in vitro passive permeability determination were found to be key in guiding SAR and improve oral exposure of renin inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.
The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization.
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.
NASA Astrophysics Data System (ADS)
Zhao, Q. L.; Si, J. L.; Guo, Z. Y.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Li, X. Y.; Guo, X.; Zhong, H. Q.; Li, L. Q.
2011-01-01
We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G.
Tracer kinetic modelling for DCE-MRI quantification of subtle blood-brain barrier permeability.
Heye, Anna K; Thrippleton, Michael J; Armitage, Paul A; Valdés Hernández, Maria Del C; Makin, Stephen D; Glatz, Andreas; Sakka, Eleni; Wardlaw, Joanna M
2016-01-15
There is evidence that subtle breakdown of the blood-brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n=201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a "sham" DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and K(Trans) estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low-permeability states, which has the potential to provide valuable information regarding BBB integrity in a range of diseases. However, absolute values of the resulting tracer kinetic parameters should be interpreted with extreme caution, and the size and influence of signal drift should be measured where possible. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Tracer kinetic modelling for DCE-MRI quantification of subtle blood–brain barrier permeability
Heye, Anna K.; Thrippleton, Michael J.; Armitage, Paul A.; Valdés Hernández, Maria del C.; Makin, Stephen D.; Glatz, Andreas; Sakka, Eleni; Wardlaw, Joanna M.
2016-01-01
There is evidence that subtle breakdown of the blood–brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n = 201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a “sham” DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and KTrans estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low-permeability states, which has the potential to provide valuable information regarding BBB integrity in a range of diseases. However, absolute values of the resulting tracer kinetic parameters should be interpreted with extreme caution, and the size and influence of signal drift should be measured where possible. PMID:26477653
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lambert, M.L.; Cole, R.D.
1996-01-01
The Tocito Sandstone Member of the Mancos Shale is an Upper Cretaceous shallow-marine sandstone and mudrock complex deposited along the western margin of the Western Interior seaway. The Tocito is a major hydrocarbon producer in the San Juan Basin (approximately 117 million barrels of oil and 79 billion cubic feet of gas). Because of reservoir heterogeneity, ultimate Tocito oil recovery factors are low, generally between 10 and 20 percent. To enhance understanding of permeability heterogeneity in the Tocito, we have undertaken a detailed surface and subsurface investigation. A total of 2,697 permeability measurements have been made using minipermeameters. Permeability variationmore » within the Tocito is controlled by two principal factors: lithofacies and burial/diagenetic history. Coarser grained and better sorted lithofacies have the highest permeability. The permeability values from outcrop and shallow subsurface cores are dramatically higher than those from deep subsurface cores. This is due to dissolution of grains and calcite cement, and decompaction that preferentially affected the outcrop and shallow subsurface. Correlation lengths for permeability values along horizontal transacts are typically less than 3 m, whereas those for vertical transacts are usually less than 0.6 m. These data suggest that small grid block sizes should be used during reservoir simulations if the investigator wishes to accurately capture the reservoir heterogeneity.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lambert, M.L.; Cole, R.D.
1996-12-31
The Tocito Sandstone Member of the Mancos Shale is an Upper Cretaceous shallow-marine sandstone and mudrock complex deposited along the western margin of the Western Interior seaway. The Tocito is a major hydrocarbon producer in the San Juan Basin (approximately 117 million barrels of oil and 79 billion cubic feet of gas). Because of reservoir heterogeneity, ultimate Tocito oil recovery factors are low, generally between 10 and 20 percent. To enhance understanding of permeability heterogeneity in the Tocito, we have undertaken a detailed surface and subsurface investigation. A total of 2,697 permeability measurements have been made using minipermeameters. Permeability variationmore » within the Tocito is controlled by two principal factors: lithofacies and burial/diagenetic history. Coarser grained and better sorted lithofacies have the highest permeability. The permeability values from outcrop and shallow subsurface cores are dramatically higher than those from deep subsurface cores. This is due to dissolution of grains and calcite cement, and decompaction that preferentially affected the outcrop and shallow subsurface. Correlation lengths for permeability values along horizontal transacts are typically less than 3 m, whereas those for vertical transacts are usually less than 0.6 m. These data suggest that small grid block sizes should be used during reservoir simulations if the investigator wishes to accurately capture the reservoir heterogeneity.« less
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.
Prevette, Lisa E.; Mullen, Douglas G.; Banaszak Holl, Mark M.
2010-01-01
Polycationic materials commonly used to delivery DNA to cells are known to induce cell membrane porosity in a charge-density dependent manner. It has been suggested that these pores may provide a mode of entry of the polymer-DNA complexes (polyplexes) into cells. To examine the correlation between membrane permeability and biological activity, we used two-color flow cytometry on two mammalian cell lines to simultaneously measure gene expression of a plasmid DNA delivered with four common nonviral vectors and cellular uptake of normally excluded fluorescent dye molecules of two different sizes, 668 Da and 2 MDa. We also followed gene expression in cells sorted based on the retention of endogenous fluorescein. We have found that cell membrane porosity caused by polycationic vectors does not enhance internalization or gene expression. Based on this single-cell study, membrane permeability is found to be an unwanted side effect that limits transfection efficiency, possibly through leakage of the delivered nucleic acid through the pores prior to transcription and translation and/or activation of cell defense mechanisms that restrict transgene expression. PMID:20349965
Zhu, Zhiwen; Zhu, Li; Li, Jianrong; Tang, Jianfeng; Li, Gang; Hsieh, Yi-Kong; Wang, TsingHai; Wang, Chu-Fang
2016-03-15
The consideration of water energy nexus inspires the environmental engineering community to pursue a more sustainable strategy in the wastewater treatment. One potential response would be to enhance the performance of the low-pressure driven filtration system. To reach this objective, it is essential to have a better understanding regarding the surface interaction between the target substance and the surface of membrane. In this study, the hollow fiber ceramic membranes were coated with a goethite layer in order to enhance the Co(2+) rejection. Experimental results indicate that higher Co(2+) rejections are always accompanied with the significant reduction in the permeability. Based on the consideration of electroviscous effect, the surface interactions including the induced changes in viscosity, pore radius and Donnan effect in the goethite layer are likely responsible for the pH dependent behaviors in the rejection and permeability. These results could be valuable references to develop the filtration system with high rejection along with acceptable degree of permeability in the future. Copyright © 2015 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Taniguchi, Ikuo; Wada, Norihisa; Kinugasa, Kae; Higa, Mitsuru
2017-11-01
Due to CO2-philic nature of polyoxyethylene (POE), a dense POE comb structure was tethered onto PMMA backbone to develop CO2 separation membranes over N2. The resulting hyper-branched polymers displayed preferential CO2 permeation. When the polymer thin layer was formed on a high gas permeable polydimethylsiloxane (PDMS) support by a spray-coating manner, the resulting thin film composite (TFC) membranes displayed very high CO2 permeability. However, the CO2 selectivity, which was the permeability ratio of CO2 over N2, was moderate and lower than 50. To enhance the selectivity, poly(amidoamine) (PAMAM) was introduced to the hyper-branched polymers in the CO2-selective layer of the TFC membranes. The CO2 selectivity increased from 47 to 90 with increasing PAMAM content to 40 wt%, and it was drastically enhanced to 350 with PAMAM content of 50 wt%. Differential scanning calorimetry (DSC) and laser microscope revealed formation of PAMAM-rich domain at the higher amine content, where CO2 could readily migrate in comparison to the other polymeric fractions.
Learning from our failures in blood-brain permeability: what can be done for new drug discovery?
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.
Computational Studies of Drug Release, Transport and Absorption in the Human Intestines
NASA Astrophysics Data System (ADS)
Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.
2016-11-01
Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.
Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, themore » released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.« less
Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar
2011-08-01
Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.
Quasi-equilibrium analysis of the ion-pair mediated membrane transport of low-permeability drugs.
Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L
2009-07-01
The aim of this research was to gain a mechanistic understanding of ion-pair mediated membrane transport of low-permeability drugs. Quasi-equilibrium mass transport analyses were developed to describe the ion-pair mediated octanol-buffer partitioning and hydrophobic membrane permeation of the model basic drug phenformin. Three lipophilic counterions were employed: p-toluenesulfonic acid, 2-naphthalenesulfonic acid, and 1-hydroxy-2-naphthoic acid (HNAP). Association constants and intrinsic octanol-buffer partition coefficients (Log P(AB)) of the ion-pairs were obtained by fitting a transport model to double reciprocal plots of apparent octanol-buffer distribution coefficients versus counterion concentration. All three counterions enhanced the lipophilicity of phenformin, with HNAP providing the greatest increase in Log P(AB), 3.7 units over phenformin alone. HNAP also enhanced the apparent membrane permeability of phenformin, 27-fold in the PAMPA model, and 4.9-fold across Caco-2 cell monolayers. As predicted from a quasi-equilibrium analysis of ion-pair mediated membrane transport, an order of magnitude increase in phenformin flux was observed per log increase in counterion concentration, such that log-log plots of phenformin flux versus HNAP concentration gave linear relationships. These results provide increased understanding of the underlying mechanisms of ion-pair mediated membrane transport, emphasizing the potential of this approach to enable oral delivery of low-permeability drugs.
Filatov, V V
2005-01-01
This paper deals with the study of infrasound phonophoresis-induced changes in biochemical factors, which affect the permeability of eyeball tissues. During 10 days, the rabbit right eye was exposed to an infrasound in the changing pressure mode at 4 Hz and 173 dB for 10 minutes every day. The left eye remained control. After finishing a series of studies, the animals were slaughtered, the eyes were enucleated and prepared into individual tissues. Changes in sodium-potassium composition were investigated in the first series. By causing a reduction in the cellular content of K+, infrasound exposure was found to cause a decrease in membranous potential and activation Na-channel, as confirmed by the elevated intracellular levels of Na+. This in turn enhances ocular tissue permeability for drugs without damaging the structure of a cell membrane. Changes in the activity of the following enzymes: beta-glucosidase, cathepsin D, and hy- aluronidase. Infrasound was ascertained to enhance the activity of beta-glucosidase, which accounts for the lower levels of glucose in ocular tissues and points to the activation and acceleration of biochemical processes in the tissues. At the same time the increased concentrations of cathepsin D and hyaluronidase found in ocular tissues were responsible for a temporary reduction in the viscosity of hyaluronic acid, which promotes resolution of opacities, adhesions or scars and increased tissue permeability.
Lerner, Aaron; Matthias, Torsten
2015-06-01
The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression. Copyright © 2015. Published by Elsevier B.V.
Zhang, Renduo; Wood, A Lynn; Enfield, Carl G; Jeong, Seung-Woo
2003-01-01
Stochastical analysis was performed to assess the effect of soil spatial variability and heterogeneity on the recovery of denser-than-water nonaqueous phase liquids (DNAPL) during the process of surfactant-enhanced remediation. UTCHEM, a three-dimensional, multicomponent, multiphase, compositional model, was used to simulate water flow and chemical transport processes in heterogeneous soils. Soil spatial variability and heterogeneity were accounted for by considering the soil permeability as a spatial random variable and a geostatistical method was used to generate random distributions of the permeability. The randomly generated permeability fields were incorporated into UTCHEM to simulate DNAPL transport in heterogeneous media and stochastical analysis was conducted based on the simulated results. From the analysis, an exponential relationship between average DNAPL recovery and soil heterogeneity (defined as the standard deviation of log of permeability) was established with a coefficient of determination (r2) of 0.991, which indicated that DNAPL recovery decreased exponentially with increasing soil heterogeneity. Temporal and spatial distributions of relative saturations in the water phase, DNAPL, and microemulsion in heterogeneous soils were compared with those in homogeneous soils and related to soil heterogeneity. Cleanup time and uncertainty to determine DNAPL distributions in heterogeneous soils were also quantified. The study would provide useful information to design strategies for the characterization and remediation of nonaqueous phase liquid-contaminated soils with spatial variability and heterogeneity.
A numerical model of surfactant enhanced solubilization was developed and applied to the simulation of nonaqueous phase liquid recovery in two-dimensional heterogeneous laboratory sand tank systems. Model parameters were derived from independent, small-scale, ...
Modeling the effects of hydraulic stimulation on geothermal reservoirs
NASA Astrophysics Data System (ADS)
De Simone, Silvia; Vilarrasa, Victor; Carrera, Jesús; Alcolea, Andrés; Meier, Peter
2013-04-01
Geothermal energy represents a huge power source that can provide clean energy in potentially unlimited supply. When designing geothermal energy production from deep hot rocks, permeability is considered to control the economic efficiency of the heat extraction operations. In fact, a high permeability heat exchanger is required to achieve a cost-competitive power generation. The typical procedure entails intercepting naturally fractured rocks and enhancing their permeability by means of stimulation. Hydraulic stimulation is the most widely used method. It involves the massive injection of a large volume of water at high flow rates to increase the downhole pore pressure. This overpressure reduces the effective stresses, which tends to induce shearing along the fracture planes. In this way permeability is enhanced due to dilatancy, especially in the direction perpendicular to shear. These processes usually trigger microseismic events, which are sometimes of sufficient magnitude to be felt by the local population. This causes a negative impact on the local population and may compromise the continuation of the project. Hence, understanding the mechanisms triggering these induced micro-earthquakes is important to properly design and manage geothermal stimulation and operations so as to prevent them. We analyzed the thermo-hydro-mechanical response of a fractured deep rock mass subjected to hydraulic stimulation. Considering that seismicity is triggered when failure condition are reached, we studied the variation of the stress regime due to the hydraulic and thermal perturbations during fluid injection. Starting with a simplified model with constant permeability fault zones, more sophisticated schemes are considered to simulate the behavior of the discontinuity zones, including permeability variation associated to temperature, pressure and stress regime changes. Numerical simulations are performed using the finite element numerical code CODE_BRIGHT, which allows to solve fully coupled thermo-hydro-mechanical problems. Results allowed to estimate the impact of the hydraulic stimulation on the overall behavior.
Yang, Mingjun; Wang, Bo; Gao, Jufang; Zhang, Yang; Xu, Wenping; Tao, Liming
2017-02-01
Spinosad, a reduced-risk insecticide, acts on the nicotinic acetylcholine receptors and the gamma-aminobutyric acid receptor in the nervous system of target insects. However, its mechanism of action in non-neural insect cells is unclear. This study aimed to evaluate mitochondrial functional changes associated with spinosad in Spodoptera frugiperda (Sf9) insect cells. Our results indicate that in Sf9 cells, spinosad induces programmed cell death and mitochondrial dysfunction through enhanced reactive oxygen species production, mitochondrial permeability transition pore (mPTP) opening, and mitochondrial membrane potential collapse, eventually leading to cytochrome C release and apoptosis. The cytochrome C release induced by spinosad treatment was partly inhibited by the mPTP inhibitors cyclosporin A and bongkrekic acid. Subsequently, we found that spinosad downregulated Bcl-2 expression and upregulated p53 and Bax expressions, activated caspase-9 and caspase-3, and triggered PARP cleavage in Sf9 cells. These findings suggested that spinosad-induced programmed cell death was modulated by mitochondrial dysfunction and cytochrome C release. Copyright © 2016 Elsevier Ltd. All rights reserved.
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
Novel transmucosal absorption enhancers obtained by aminoalkylation of chitosan.
Zambito, Ylenia; Uccello-Barretta, Gloria; Zaino, Chiara; Balzano, Federica; Di Colo, Giacomo
2006-12-01
Literature data suggest that quaternized chitosans have a transmucosal drug absorption enhancing property depending on their MW, quaternization degree and other structural features. With the purpose of preparing novel effective promoters, a chitosan (Ch) from crab shell (ChC; viscometric MW, 800 kDa; deacetylation: 90%, IR; 84%, NMR) and one from shrimp shell (ChS; viscometric MW, 590 kDa; deacetylation: 90%, IR; 82%, NMR) were reacted with 2-diethylaminoethyl chloride (DEAE-Cl) and novel derivatives containing different percentages of pendant quaternary ammonium groups were obtained. NMR analysis, based on HSQC, COSY, TOCSY and ROESY maps, indicated that three partially substituted N,O-[N,N-diethylaminomethyl(diethyldimethylene ammonium)(n)]methyl chitosans, coded N(+)-ChS-2 (degree of substitution, DS=40%; n=1.6), N(+)-ChS-4 (DS=132%; n=2.5), and N(+)-ChC-4 (DS=85%; n=1.7) resulted from the reaction, depending on whether the DEAE-Cl/Ch repeating unit molar ratio, was 2:1 or 4:1. The effects of the derivatives on the permeability of rhodamine 123 (Rh-123), hydrophobic, marker of the transcellular absorption route, and of fluorescein sodium (NaFlu), polar, marker of the paracellular route, across excised porcine cheek epithelium were assessed, using Franz type diffusion cells. Rh-123 permeability was enhanced by N(+)-ChS-4 (enhancement ratio, ER=8.4) and by N(+)-ChC-4 (ER=3.9), whereas N(+)-ChS-2 was ineffective. NaFlu permeability was enhanced by N(+)-ChS-2 (ER=7.2), N(+)-ChS-4 (ER=7.4) and N(+)-ChC-4 (ER=6.6). In conclusion, the three derivatives, whichever their DS, promote paracellular transport, while transcellular transport is substantially accelerated only by the most substituted one.
Song, Qinxin; Li, Danhui; Zhou, Yongzhi; Yang, Jie; Yang, Wanqi; Zhou, Guohua; Wen, Jingyuan
2014-01-01
The aim of this study was to evaluate (+)-catechin and (−)-epigallocatechin gallate (EGCG) cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.22±0.16, 0.90±0.14, 3.25±0.37, and 1.92±0.22 μg/mg protein, respectively (n=3). The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.68±0.16, 0.88±0.09, 2.39±0.31, and 1.42±0.24 cm/second (n=3) at 37°C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation significantly enhanced drug absorption. Additionally, drug-loaded niosomes exhibited stronger stability and lower toxicity. These findings showed that the oral absorption of tea flavonoids could be improved by using the novel drug delivery systems. PMID:24855353
Transporter targeted gatifloxacin prodrugs: Synthesis, permeability, and topical ocular delivery
Vooturi, Sunil K.; Kadam, Rajendra S.; Kompella, Uday B.
2013-01-01
Purpose To design and synthesize prodrugs of gatifloxacin targeting OCT, MCT, and ATB (0, +) transporters and to identify a prodrug with enhanced delivery to the back of the eye. Method Dimethylamino-propyl, carboxy-propyl, and amino-propyl(2-methyl) derivatives of gatifloxacin (GFX), DMAP-GFX, CP-GFX, and APM-GFX, were designed and synthesized to target OCT, MCT, and ATB (0, +) transporters, respectively. LC-MS method was developed to analyze drug and prodrug levels in various studies. Solubility and Log D (pH 7.4) were measured for prodrugs and the parent drug. Permeability of the prodrugs was determined in cornea, conjunctiva, and sclera-choroidretinal pigment epitheluim (SCRPE) and compared with gatifloxacin using Ussing chamber assembly. Permeability mechanisms were elucidated by determining the transport in the presence of transporter specific inhibitors. 1-Methyl-4-phenylpyridinium iodide (MPP+), nicotinic acid sodium salt, and α-methyl-DL-tryptophan were used to inhibit OCT, MCT, and ATB (0, +) transporters, respectively. A prodrug selected based on in vitro studies was administered as an eye drop to pigmented rabbits and the delivery to various eye tissues including vitreous humor was compared with gatifloxacin dosing. Results DMAP-GFX exhibited 12.8-fold greater solubility than GFX. All prodrugs were more lipophilic, with the measured Log D (pH 7.4) values ranging from 0.05 to 1.04, when compared to GFX (Log D: -1.15). DMAP-GFX showed 1.4-, 1.8-, and 1.9-fold improvement in permeability across cornea, conjunctiva, as well as SCRPE when compared to GFX. Moreover, it exhibited reduced permeability in the presence of MPP+ (competitive inhibitor of OCT), indicating OCT-mediated transport. CP-GFX showed 1.2-, 2.3- and 2.5-fold improvement in permeability across cornea, conjunctiva and SCRPE, respectively. In the presence of nicotinic acid (competitive inhibitor of MCT), permeability of CP-GFX was reduced across conjunctiva. However, cornea and SCRPE permeability of CP-GFX was not affected by nicotinic acid. APM-GFX did not show any improvement in permeability when compared to GFX across cornea, conjunctiva, and SCRPE. Based on solubility and permeability, DMAP-GFX was selected for in vivo studies. DMAP-GFX showed 3.6- and 1.95-fold higher levels in vitreous humor and CRPE compared to that of GFX at 1 hour after topical dosing. In vivo conversion of DMAP-GFX prodrug to GFX was quantified in tissues isolated at 1 hour after dosing. Prodrug-to-parent drug ratio was 8, 70, 24, 21, 29, 13, 55, and 60 % in cornea, conjunctiva, iris-ciliary body, aqueous humor, sclera, CRPE, retina, and vitreous humor, respectively. Conclusions DMAP-GFX prodrug enhanced solubility, Log D, as well as OCT mediated delivery of gatifloxacin to the back of the eye. PMID:23003105
Copoví, A; Díez-Sales, O; Herráez-Domínguez, J V; Herráez-Domínguez, M
2006-05-11
The percutaneous penetration-enhancing effects of glycolic acid, lactic acid and sodium lauryl sulphate through the human epidermis was investigated using 5-fluorouracil as a hydrophilic model permeant and three compounds belonging to the phenylalcohols: 2-phenyl-ethanol, 4-phenyl-butanol and 5-phenyl-pentanol. The lipophilicity values of the compounds ranged from log Poct -0.95 to 2.89. The effect of the enhancer concentration was also studied. Skin pretreatment with aqueous solutions of the three enhancers did not increase the permeability coefficient of the most lipophilic compound (log Poct = 2.89). For the other compounds assayed, the increase in the permeability coefficients depended on the concentration used in skin pretreatment, and on the lipophilicity of the compounds tested-and was always greater for the most hydrophilic compound (5-fluorouracil), for which lactic acid exerted a greater enhancer effect than glycolic acid or sodium lauryl sulphate. Primary irritation testing of the three enhancers was also carried out at the two concentrations used in skin pretreatment for diffusional experiments (1% and 5%, w/w). The least irritant capacity corresponded to lactic acid; consequently, this alpha-hydroxyacid could be proposed as a percutaneous penetration enhancer for hydrophilic molecules that are of interest for transdermal administration.
Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.
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.
Scholz, Miklas; Uzomah, Vincent C
2013-08-01
The retrofitting of sustainable drainage systems (SuDS) such as permeable pavements is currently undertaken ad hoc using expert experience supported by minimal guidance based predominantly on hard engineering variables. There is a lack of practical decision support tools useful for a rapid assessment of the potential of ecosystem services when retrofitting permeable pavements in urban areas that either feature existing trees or should be planted with trees in the near future. Thus the aim of this paper is to develop an innovative rapid decision support tool based on novel ecosystem service variables for retrofitting of permeable pavement systems close to trees. This unique tool proposes the retrofitting of permeable pavements that obtained the highest ecosystem service score for a specific urban site enhanced by the presence of trees. This approach is based on a novel ecosystem service philosophy adapted to permeable pavements rather than on traditional engineering judgement associated with variables based on quick community and environment assessments. For an example case study area such as Greater Manchester, which was dominated by Sycamore and Common Lime, a comparison with the traditional approach of determining community and environment variables indicates that permeable pavements are generally a preferred SuDS option. Permeable pavements combined with urban trees received relatively high scores, because of their great potential impact in terms of water and air quality improvement, and flood control, respectively. The outcomes of this paper are likely to lead to more combined permeable pavement and tree systems in the urban landscape, which are beneficial for humans and the environment. Copyright © 2013 Elsevier B.V. All rights reserved.
Intestinal Permeability of β-Lapachone and Its Cyclodextrin Complexes and Physical Mixtures.
Mangas-Sanjuan, Victor; Gutiérrez-Nieto, Jorge; Echezarreta-López, Magdalena; González-Álvarez, Isabel; González-Álvarez, Marta; Casabó, Vicente-Germán; Bermejo, Marival; Landin, Mariana
2016-12-01
β-Lapachone (βLAP) is a promising, poorly soluble, antitumoral drug. βLAP combination with cyclodextrins (CDs) improves its solubility and dissolution but there is not enough information about the impact of cyclodextrins on βLAP intestinal permeability. The objectives of this work were to characterize βLAP intestinal permeability and to elucidate cyclodextrins effect on the dissolution properties and on the intestinal permeability. The final goal was to evaluate CDs influence on the oral absorption of βLAP. Binary systems (physical mixtures and inclusion complexes) including βLAP and CDs (β-cyclodextrin: βCD, random-methyl-β-cyclodextrin: RMβCD and sulfobutylether-β-cyclodextrin: SBEβCD) have been prepared and analysed by differential scanning calorimetry. βLAP (and its combinations with CDs) absorption rate coefficients and effective permeability values have been determined in vitro in MDCK or MDCK-Mdr1 monolayers and in situ in rat by a closed loop perfusion technique. DSC results confirmed the formation of the inclusion complexes. βLAP-CDs inclusion complexes improve drug solubility and dissolution rate in comparison with physical mixtures. βLAP presented a high permeability value which can provide complete oral absorption. Its oral absorption is limited by its low solubility and dissolution rate. Cyclodextrin (both as physical mixtures and inclusion complexes) showed a positive effect on the intestinal permeability of βLAP. Complexation with CDs does not reduce βLAP intestinal permeability in spite of the potential negative effect of the reduction in free fraction of the drug. The use of RMβCD or SBEβCD inclusion complexes could benefit βLAP oral absorption by enhancing its solubility, dissolution rate and permeability.
Glutamate-Mediated Blood–Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery
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
NASA Astrophysics Data System (ADS)
Jia, Wei; McPherson, Brian; Pan, Feng; Dai, Zhenxue; Moodie, Nathan; Xiao, Ting
2018-02-01
Geological CO2 sequestration in conjunction with enhanced oil recovery (CO2-EOR) includes complex multiphase flow processes compared to CO2 storage in deep saline aquifers. Two of the most important factors affecting multiphase flow in CO2-EOR are three-phase relative permeability and associated hysteresis, both of which are difficult to measure and are usually represented by numerical interpolation models. The purpose of this study is to improve understanding of (1) the relative impacts of different three-phase relative permeability models and hysteresis models on CO2 trapping mechanisms, and (2) uncertainty associated with these two factors. Four different three-phase relative permeability models and three hysteresis models were applied to simulations of an active CO2-EOR site, the SACROC unit located in western Texas. To eliminate possible bias of deterministic parameters, we utilized a sequential Gaussian simulation technique to generate 50 realizations to describe heterogeneity of porosity and permeability, based on data obtained from well logs and seismic survey. Simulation results of forecasted CO2 storage suggested that (1) the choice of three-phase relative permeability model and hysteresis model led to noticeable impacts on forecasted CO2 sequestration capacity; (2) impacts of three-phase relative permeability models and hysteresis models on CO2 trapping are small during the CO2-EOR injection period, and increase during the post-EOR CO2 injection period; (3) the specific choice of hysteresis model is more important relative to the choice of three-phase relative permeability model; and (4) using the recommended three-phase WAG (Water-Alternating-Gas) hysteresis model may increase the impact of three-phase relative permeability models and uncertainty due to heterogeneity.
Improved oil recovery using bacteria isolated from North Sea petroleum reservoirs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Davey, R.A.; Lappin-Scott, H.
1995-12-31
During secondary oil recovery, water is injected into the formation to sweep out the residual oil. The injected water, however, follows the path of least resistance through the high-permeability zones, leaving oil in the low-permeability zones. Selective plugging of these their zones would divert the waterflood to the residual oil and thus increase the life of the well. Bacteria have been suggested as an alternative plugging agent to the current method of polymer injection. Starved bacteria can penetrate deeply into rock formations where they attach to the rock surfaces, and given the right nutrients can grow and produce exo-polymer, reducingmore » the permeability of these zones. The application of microbial enhanced oil recovery has only been applied to shallow, cool, onshore fields to date. This study has focused on the ability of bacteria to enhance oil recovery offshore in the North Sea, where the environment can be considered extreme. A screen of produced water from oil reservoirs (and other extreme subterranean environments) was undertaken, and two bacteria were chosen for further work. These two isolates were able to grow and survive in the presence of saline formation waters at a range of temperatures above 50{degrees}C as facultative anaerobes. When a solution of isolates was passed through sandpacks and nutrients were added, significant reductions in permeabilities were achieved. This was confirmed in Clashach sandstone at 255 bar, when a reduction of 88% in permeability was obtained. Both isolates can survive nutrient starvation, which may improve penetration through the reservoir. Thus, the isolates show potential for field trials in the North Sea as plugging agents.« less
Tamakuwala, M; Stagni, G
2016-08-01
Fingolimod (FNGL) is an immune-modulatory agent prescribed for relapsing forms of multiple sclerosis. Because of its mechanism of action, FNGL is potentially a treatment for chronic, non-curable T-lymphocyte-driven inflammatory skin diseases (TLDISD) such as psoriasis and atopic dermatitis. Since severe side effects limit the systemic administration of FNGL, the objective of this study is to develop a hydroxypropyl cellulose (2%) FNGL gel for dermatological applications. First, the effect of FNGL strength (0.05%, 0.10%, 0.50%, and 1.00%) on skin permeability and retention was investigated. We carried out several permeation studies with vertical Franz diffusion cells and (i) cellulose or (ii) excised dorsal porcine ear skin (EDPES) as membrane. We also quantified FNGL in the stratum corneum and in dermis with the tape-stripping method. Permeability parameters as well as the amount retained in skin increased significantly (p < 0.01) with strength; however, there was no statistically significant difference between the 0.50% and 1.00% gels for both cellulose and EDPES. Therefore, we selected the 0.50% gel to investigate the effect of colloidal oatmeal (0%, 1%, 3%, 6%, and 10%) on FNGL in vitro permeability and skin retention. Colloidal oatmeal has beneficial dermatological properties for TLDISD and may complement FNGL activity. Permeability increased significantly (p < 0.001) with colloidal oatmeal at the 6% and 10% strength with an enhancement ratio of 3.5 and 2.4, respectively, whereas the amount retained in the skin decreased significantly (p < 0.001) compared to the base gel. In conclusion, the 0.50% FNGL(.)HCL gel with 6% Aveeno® has very promising permeability characteristics for delivery of FNGL to the skin.
Inhibition of basolateral cAMP permeability in the toad urinary bladder.
Boom, A; Golstein, P E; Frerotte, M; Sande, J V; Beauwens, R
2000-10-01
1. The effect of sulphonylurea drugs on hydrosmotic flow across toad urinary bladder epithelium was re-evaluated in the present study. Glibenclamide, added to the basolateral medium, significantly enhanced the osmotic flow induced by low doses of antidiuretic hormone (ADH) or forskolin (FK), while it inhibited the effect of exogenous cyclic adenosine monophosphate (cAMP) or its non-hydrolysable bromo derivative, 8-Br-cAMP, added to the basolateral medium. These opposite effects of glibenclamide on the transepithelial osmotic flow can be explained by a reduction of cAMP permeability across the basolateral membrane of the epithelium. The decrease in cAMP permeability leads, according to the direction of the cAMP gradient, to firstly an enhanced osmotic flow when cAMP is generated intracellularly by addition of ADH and FK, glibenclamide reducing cAMP exit from the cell, and secondly a decreased osmotic flow in response to cAMP (and 8-Br-cAMP) added to the basolateral medium, glibenclamide inhibiting, in this case, their entry into the cell. 2. The demonstration that glibenclamide actually inhibits the basolateral cAMP permeability rests on the fact that firstly it decreases the release of cAMP into the basolateral medium by about 40 %, at each concentration of ADH or forskolin tested, secondly it increases the cAMP content of paired hemibladders incubated in the presence of ADH or FK, when intracellular degradation was prevented by phosphodiesterase inhibition, and thirdly it decreases also the uptake of basolateral 8-Br-[3H]cAMP into paired toad hemibladders. 3. Taken together, the present data demonstrate that glibenclamide inhibits the toad urinary bladder basolateral membrane permeability to cAMP, most probably by a direct interaction with a membrane protein not yet indentified but distinct from the sulphonylurea receptor.
Perturbation of host-cell membrane is a primary mechanism of HIV cytopathology.
Cloyd, M W; Lynn, W S
1991-04-01
Cytopathic viruses injure cells by a number of different mechanisms. The mechanism by which HIV-1 injures T cells was studied by temporally examining host-cell macromolecular syntheses, stages of the cell cycle, and membrane permeability following acute infection. T cells cytopathically infected at an m.o.i. of 1-5 grew normally for 24-72 hr, depending on the cell line, followed by the first manifestation of cell injury, slowing of cell division. At that time significant amounts of unintegrated HIV DNA and p24 core protein became detectable, and acridine orange flow cytometric cell cycle studies demonstrated the presence of fewer cells in the G2/M stage of the cell cycle. There was no change in the frequency of cells in the S-stage, and metabolic pulsing with radioactive precursors demonstrated that host-cell DNA, RNA, and protein syntheses were normal at that time and normal up to the time cells started to die (approximately 24 hr later), when all three decreased. Cellular lipid synthesis, however, was perturbed when cell multiplication slowed, with phospholipid synthesis reduced and neutral lipid synthesis enhanced. Permeability of the host-cell membrane to small molecules, such as Ca2+ and sucrose, was slightly enhanced early postinfection, and by the time of slowing of cell division, host membrane permeability was greatly increased to both Ca2+ and sucrose (Stokes radius 5.2 A) but not to inulin (Stokes radium 20 A). These changes in host-cell membrane permeability and phospholipid synthesis were not observed in acutely infected H9 cells, which are not susceptible to HIV cytopathology. Thus, HIV-1 appeared to predominantly injure T cells by perturbing host-cell membrane permeability and lipid synthesis, which is similar to the cytopathic mechanisms of paramyxoviruses.
Okada, Maki; Kikuchi, Tatsuya; Okamura, Toshimitsu; Ikoma, Yoko; Tsuji, Atsushi B; Wakizaka, Hidekatsu; Kamakura, Tomoo; Aoki, Ichio; Zhang, Ming-Rong; Kato, Koichi
2015-12-01
The blood-brain barrier (BBB) limits the entry of some therapeutics into the brain, resulting in reduced efficacy. BBB-opening techniques have been developed to enhance the entry into the brain. However, a noninvasive, highly sensitive and quantitative method for evaluating the changes in BBB permeability induced by such techniques is needed to optimize treatment protocols. We evaluated 2-amino-[3-C]isobutyric acid ([3-C]AIB) as a PET probe to quantify BBB permeability in model rats. BBB opening was induced by a lipopolysaccharide injection or focused ultrasound (FUS) sonication. [3-C]AIB distribution in the brain was evaluated by autoradiography and PET and compared with that of Evans blue, a traditional BBB permeability marker. Kinetics of [3-C]AIB was compared with that of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI. The unidirectional blood-brain transfer constant (Ki) of [3-C]AIB was estimated using the Patlak plot. [3-C]AIB uptake in the lesion area was significantly higher than that in the control area and radioactivity colocalized with Evans blue in both models. [3-C]AIB uptake in the FUS-sonicated region decreased over time after sonication. The ratio of [3-C]AIB accumulation in the FUS-treated to the contralateral side increased during the experimental period, whereas that of the Gd-DTPA intensity reached a maximum at 10 min after injection and decreased thereafter. The [3-C]AIB Ki values were significantly higher in the lesion area than the control area. [3-C]AIB PET is a promising, highly sensitive and quantitative imaging method for assessment of BBB permeability.
NASA Astrophysics Data System (ADS)
Witte, B.; Ferlin, C.; Gallo, E. L.; Lohse, K. A.; Meixner, T.; Brooks, P. D.; Ferre, T. A.
2010-12-01
Storm water infiltration and recharge is a key component of sustainable water resource management in rapidly expanding urban areas of arid and semi-arid regions. Near surface streambed permeability affects the partitioning of stream flows to infiltration and subsequent groundwater recharge, or increasing runoff to be conveyed downstream. Therefore, in this study, we assessed how air permeability varied among distinct stream beds of ephemeral urban washes in the semi-arid southwest. A Soil Core Air Permeameter (SCAP) was used to quantify in situ air permeability at sixteen sites in the Tucson, Arizona metropolitan area. Significant air permeability differences between gravel and grass lined ephemeral stream beds were found, where the average air permeability at the gravel sites was 3.58 x10-2 ± 1.11 x 10-2 mm2 (mean ± std error) and the air permeability at the grass sites was 7.13 x 10-3 ± 2.02 x 10-3 mm2. A previously published linear correlation between air permeability and saturated hydraulic conductivity was used to predict saturated hydraulic conductivity at the ephemeral stream beds of this study. Preliminary results suggest that the predicted saturated hydraulic conductivity values are comparable to ring infiltration measurements taken in the field. Findings from this study indicate that the higher porosity and decreased vegetation at the gravel lined urban washes enhanced infiltration rates, which may lead to decreased storm water runoff. However, higher infiltration rates at gravel lined sites may result in less time for processing of potential pollutants with negative implications for water quality.
Pervin, Monira; Unno, Keiko; Nakagawa, Aimi; Takahashi, Yuu; Iguchi, Kazuaki; Yamamoto, Hiroyuki; Hoshino, Minoru; Hara, Aya; Takagaki, Akiko; Nanjo, Fumio; Minami, Akira; Imai, Shinjiro; Nakamura, Yoriyuki
2017-03-01
The consumption of green tea catechins (GTCs) suppresses age-related cognitive dysfunction in mice. GTCs are composed of several catechins, of which epigallocatechin gallate (EGCG) is the most abundant, followed by epigallocatechin (EGC). Orally ingested EGCG is hydrolyzed by intestinal biota to EGC and gallic acid (GA). To understand the mechanism of action of GTCs on the brain, their permeability of the blood brain barrier (BBB) as well as their effects on cognitive function in mice and on nerve cell proliferation in vitro were examined. The BBB permeability of EGCG, EGC and GA was examined using a BBB model kit. SAMP10, a mouse model of brain senescence, was used to test cognitive function in vivo . Human neuroblastoma SH-SY5Y cells were used to test nerve cell proliferation and differentiation. The in vitro BBB permeability (%, in 30 min) of EGCG, EGC and GA was 2.8±0.1, 3.4±0.3 and 6.5±0.6, respectively. The permeability of EGCG into the BBB indicates that EGCG reached the brain parenchyma even at a very low concentration. The learning ability of SAMP10 mice that ingested EGCG (20 mg/kg) was significantly higher than of mice that ingested EGC or GA. However, combined ingestion of EGC and GA showed a significant improvement comparable to EGCG. SH-SY5Y cell growth was significantly enhanced by 0.05 µM EGCG, but this effect was reduced at higher concentrations. The effect of EGC and GA was lower than that of EGCG at 0.05 µM. Co-administration of EGC and GA increased neurite length more than EGC or GA alone. Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.
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
Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P
2003-01-01
A membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride was developed using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 8%w/w of carvone as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38, or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28%w/w vinyl acetate) or EVA 2825 membrane/skin composite also was studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED and 2%w/w HPC gel as reservoir containing 8%w/w of carvone as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 23 hr with improved bioavailability in comparison with the immediate-release capsule dosage form.
Ashour, Eman A.; Majumdar, Soumyajit; Alsheteli, Abdulla; Alshehri, Sultan; Alsulays, Bader; Feng, Xin; Gryczke, Andreas; Kolter, Karl; Langley, Nigel; Repka, Michael A.
2016-01-01
Objective The aims of the current research project were to investigate the efficiency of various polymers to enhance the solubility and increase the systemic absorption of piperine using hot melt extrusion technology. Methods Piperine 10–40% w/w and Eudragit® EPO/ Kollidon® VA 64 or Soluplus® were mixed and the resulting blends were extruded using a twin-screw extruder (Process 11, Thermo Fisher Scientific). Drug release profiles and piperine solubility studies of the extrudates were evaluated. A non-everted intestinal sac was employed for the most promising formulation, 10% w/w piperine/Soluplus®, and pure piperine to study the permeability characteristics. Key Findings Dissolution studies demonstrated enhancement in piperine percent release of 10% and 20% w/w piperine/Soluplus® extrudates up to 95% and 74%, respectively. The solubility of 10% and 20% piperine/Soluplus® increased more than 160- and 45-fold in water, respectively. Furthermore, permeability studies demonstrated the enhancement in piperine absorption of 10% w/w piperine/Soluplus® extrudates up to 158.9 μg/5mL compared to pure piperine at 1.3 μg/5mL within 20 minutes. Conclusion These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study. PMID:27283755
Li, Wan; Zhang, Tianpeng; Ye, Yanghuan; Zhang, Xingwang; Wu, Baojian
2015-11-30
Chemotherapy via the oral route remains a considerable challenge due to poor water-solubility and permeability of anticancer agents. This study aimed to construct lipid nanoparticles using broccoli-derived lipids for oral delivery of tripterine (Tri), a natural anticancer candidate, and to enhance its oral bioavailability. Tri-loaded broccoli lipid nanoparticles (Tri-BLNs) were prepared by a solvent-diffusion method. The resulting Tri-BLNs were 75±10 nm in particle size with entrapment efficiency over 98%. In vitro release study indicated that Tri was almost not released from Tri-BLNs (<2%), whereas the lipolytic experiment showed that Tri-BLNs possessed a relatively strong anti-enzymatic degradation ability to Tri-CLNs (Tri-loaded common lipid nanoparticles). In situ single-pass intestinal perfusion manifested that the effective permeability of Tri-BLNs were significantly higher than that of Tri-CLNs. Further, Tri-BLNs exhibited more efficient cellular uptake in MDCK-II cells as evidenced by flow cytometry and confocal microscopy. The relative bioavailability of Tri-BLNs and Tri-CLNs was 494.13% and 281.95% compared with Tri suspensions, respectively. Depending on the ability in enhancement of biomembrane permeability, broccoli-derived lipids as an alternative source should be useful to construct lipid nanoparticles for bettering oral delivery of drugs with low bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.
El-Setouhy, Doaa Ahmed; Basalious, Emad B; Abdelmalak, Nevine Shawky
2015-08-01
Formulation of sublingual tablets of drugs with limited permeability poses a great challenge due to their poor absorption. In this study, bioenhanced sublingual tablets (BESTs) of zolmitriptan were prepared using novel surfactant binder (Pluronic® p123/Syloid® mixture) to enhance tablet disintegration and dissolution. Microencapsulated polysorbate 80 (Sepitrap™ 80) were included in the composition of BESTs to enhance the drug transport through the sublingual mucosa. Tablets were evaluated for in vitro/in vivo disintegration, in vitro dissolution and ex vivo permeation. Solubility studies confirmed that phosphate buffer; pH 6.8 could be used as dissolution medium for sublingual tablets of zolmitriptan. BEST-5 containing Pluronic® p123/Syloid® mixture and Sepitrap™ 80 exhibited the shortest in vitro/in vivo disintegration times (<30s), the highest dissolution at early time dissolution points and the highest enhancement of drug transport through mucosal membrane. The in vivo pharmacokinetic study using human volunteers showed a significant increase in the rate and extent of sublingual absorption with less variations of Tmax after sublingual administration of both BEST-5 and Zomig-ZMT ODT. Our results proposed that Pluronic® p123/Syloid® mixture and Sepitrap™ 80 could be promising for the development of sublingual tablets for rapid onset of action of drugs with limited permeability. Copyright © 2015 Elsevier B.V. All rights reserved.
Goel, Amit; Ahmad, Farhan Jalees; Singh, Raman Mohan; Singh, Gyanendra Nath
2010-02-01
The aim of this study was to develop 3-acetyl-11-keto-beta-boswellic acid (AKBA)-loaded polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. Polymeric nanomicelles of AKBA were developed by a radical polymerization method using N-isopropylacrylamide, vinylpyrrolidone and acrylic acid. The polymeric nanomicelles obtained were characterized by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In-vitro and in-vivo evaluations of AKBA polymeric nanomicelles gel were carried out for enhanced skin permeability and anti-inflammatory and anti-arthritic activity. TEM and DLS results demonstrated that polymeric nanomicelles were spherical with a mean diameter approximately 45 nm. FTIR data indicated a weak interaction between polymer and AKBA in the encapsulated system. The release of drug in aqueous buffer (pH 7.4) from the polymeric nanomicelles was 23 and 55% after 2 and 8 h, respectively, indicating sustained release. In-vitro skin permeation studies through excised abdominal skin indicated a threefold increase in skin permeability compared with AKBA gel containing the same amount of AKBA as the AKBA polymeric nanomicelles gel. The AKBA polymeric nanomicelle gel showed significantly enhanced anti-inflammatory and anti-arthritic activity compared with the AKBA gel. This study suggested that AKBA polymeric nanomicelle gel significantly enhanced skin permeability, and anti-inflammatory and anti-arthritic activity.
Zhang, Hongbo; Shahbazi, Mohammad-Ali; Mäkilä, Ermei M; da Silva, Tiago H; Reis, Rui L; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A
2013-12-01
Diatoms are porous silica-based materials obtained from single cell photosynthetic algae. Despite low cost, easy purification process, environmentally safe properties, and rapidly increasing potentials for medical applications, the cytotoxicity of diatoms and the effect on drug permeation of oral formulations have not been studied so far. Herein, we have evaluated the potential of diatom silica microparticles (DSMs) for the delivery of mesalamine and prednisone, which are two commonly prescribed drugs for gastrointestinal (GI) diseases. Transmission electron microscopy analysis of the morphological surface changes of Caco-2/HT-29 monolayers and the cell viability data in colon cancer cells (Caco-2, HT-29 and HCT-116) showed very low toxicity of diatoms at concentrations up to 1000 μg/mL. The mesalamine and prednisone release under simulated GI conditions indicated prolonged release of both drugs from the diatoms. Furthermore, drug permeation across Caco-2/HT-29 co-culture monolayers demonstrated that diatoms are capable to enhance the drug permeability. Overall, this study evaluated DSMs' cytotoxicity in colon cancer cells and the effect of DSMs on drug permeability across Caco-2/HT-29 monolayers. Our results demonstrate that DSMs can be considered as a non-cytotoxic biomaterial with high potential to improve the mesalamine and prednisone bioavailability by sustaining the drug release and enhancing drug permeability. Copyright © 2013 Elsevier Ltd. All rights reserved.
Data report: Compressibility, permeability, and grain size of shallow sediments, sites 1194 and 1198
Dugan, Brandon; Marone, Chris; Hong, Tiancong; Migyanka, Misty; Anselmett, Flavio S.; Isern, Alexandra R.; Blum, Peter; Betzler, Christian
2006-01-01
Uniaxial strain consolidation experiments were conducted to determine elastic and plastic properties and to estimate the permeability of sediments from 0 to 200 meters below seafloor at Ocean Drilling Program Sites 1194 and 1198. Plastic deformation is described by compression indices, which range from 0.19 to 0.37. Expansion indices, the elastic deformation measured during unload/reload cycles on samples, vary from 0.02 to 0.029. Consolidation experiments provide lower bounds on permeability between 5.4 x 10–16 m2 and 1.9 x 10–18m2, depending on the consolidation state of the sample.
Grimm, R.P.; Eriksson, K.A.; Ripepi, N.; Eble, C.; Greb, S.F.
2012-01-01
The geological storage of carbon dioxide in Appalachian basin coal seams is one possible sink for sequestration of greenhouse gases, with the added benefit of enhanced-coal bed methane (ECBM) recovery. The Pocahontas Basin (part of the central Appalachian Basin) of southwestern Virginia is a major coal bed methane (CBM) province with production mostly from coal beds in the Lower Pennsylvanian Pocahontas and New River formations. As part of the Southeast Regional Carbon Sequestration Partnership's Phase II research program, a CO 2-injection demonstration well was installed into Lower Pennsylvanian coal bed-methane producing strata in southwest Virginia. Samples of siliciclastic lithologies above coal beds in this Oakwood Field well, and from several other cores in the Nora Field were taken to establish a baseline of the basic confinement properties of overlying strata to test seal competency at local and regional scales.Strata above CBM-producing coal beds in the Pocahontas and New River formations consist of dark-gray shales; silty gray shales; heterolithic siltstones, sandstones, and shales; lithic sandstones, and quartzose sandstones. Standard measurements of porosity, permeability and petrography were used to evaluate potential leakage hazards and any possible secondary storage potential for typical lithologies. Both lithic- and quartz-rich sandstones exhibit only minor porosity, with generally low permeability (<0.042mD). Interconnected porosity and permeability are strongly impacted by diverse cementation types and compaction. Analyzed siliciclastic lithologies are considered tight, with limited primary matrix permeability risks for leakage, providing an ensemble of redundant CO 2-ECBM traps.One of the most promising confining intervals above the major coal bed-methane producing interval is the Hensley Shale Member. Analyses of 1500 geophysical logs in southwest Virginia indicate that this unit is moderately thick (>50ft, 15m), laterally continuous (>3000km 2), and a homogenous shale, which coarsens upward into siltstone and sandstone, or is truncated by sandstone. Calculations from two mercury injection capillary porosimetry tests of the shale indicate that a displacement entry pressure of 207psi (1427kPa) would generate an estimated seal capacity of 1365ft (416m) of CO 2 before buoyant leakage. Scanning electron microscopy indicates a microfabric of narrow pore throats between quartz grains floating in a clay matrix. Modeled median pore throat size between micro-fabric matrix grains for the shale is estimated at 0.26??m. These characteristics indicate that the shale, where fractures and joints are limited, would be an adequate regional confining interval for deeper CO 2 storage with ECBM. ?? 2011 Elsevier B.V.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shao, Hongbo; Kabilan, Senthil; Stephens, Sean A.
Cost-effective creation of high-permeability reservoirs inside deep crystalline bedrock is the primary challenge for the feasibility of enhanced geothermal systems (EGS). Current reservoir stimulation entails adverse environmental impacts and substantial economic costs due to the utilization of large volumes of water “doped” with chemicals including rheology modifiers, scale and corrosion inhibitors, biocides, friction reducers among others where, typically, little or no information of composition and toxicity is disclosed. An environmentally benign, CO2-activated, rheoreversible fracturing fluid has recently been developed that significantly enhances rock permeability at effective stress significantly lower than current technology. We evaluate the potential of this novel fracturingmore » fluid for application on geothermal sites under different chemical and geomechanical conditions, by performing laboratory-scale fracturing experiments with different rock sources under different confining pressures, temperatures, and pH environments. The results demonstrate that CO2-reactive aqueous solutions of environmentally amenable Polyallylamine (PAA) represent a highly versatile fracturing fluid technology. This fracturing fluid creates/propagates fracture networks through highly impermeable crystalline rock at significantly lower effective stress as compared to control experiments where no PAA was present, and permeability enhancement was significantly increased for PAA compared to conventional hydraulic fracturing controls. This was evident in all experiments, including variable rock source/type, operation pressure and temperature (over the entire range for EGS applications), as well as over a wide range of formation-water pH values. This versatile novel fracturing fluid technology represents a great alternative to industrially available fracturing fluids for cost-effective and competitive geothermal energy production.« less
Multi-dimensional computer simulation of MHD combustor hydrodynamics
NASA Astrophysics Data System (ADS)
Berry, G. F.; Chang, S. L.; Lottes, S. A.; Rimkus, W. A.
1991-04-01
Argonne National Laboratory is investigating the nonreacting jet gas mixing patterns in an MHD second stage combustor by using a 2-D multiphase hydrodynamics computer program and a 3-D single phase hydrodynamics computer program. The computer simulations are intended to enhance the understanding of flow and mixing patterns in the combustor, which in turn may lead to improvement of the downstream MHD channel performance. A 2-D steady state computer model, based on mass and momentum conservation laws for multiple gas species, is used to simulate the hydrodynamics of the combustor in which a jet of oxidizer is injected into an unconfined cross stream gas flow. A 3-D code is used to examine the effects of the side walls and the distributed jet flows on the non-reacting jet gas mixing patterns. The code solves the conservation equations of mass, momentum, and energy, and a transport equation of a turbulence parameter and allows permeable surfaces to be specified for any computational cell.
Hydraulic fracturing system and method
Ciezobka, Jordan; Salehi, Iraj
2017-02-28
A hydraulic fracturing system and method for enhancing effective permeability of earth formations to increase hydrocarbon production, enhance operation efficiency by reducing fluid entry friction due to tortuosity and perforation, and to open perforations that are either unopened or not effective using traditional techniques, by varying a pump rate and/or a flow rate to a wellbore.
Management of Contaminants Stored in Low Permeability Zones - A State of the Science Review
2013-10-01
Tank 3: Permanganate ................................................................................................... 193...Treatment options explored include steady water flushing (control), enhance water flushing, flushing permanganate , a dechlorinating culture (KB1...Remediation Tank Experiments (OoM: Order of Magnitude. PV: Pore Volume) 2. Enhanced flushing (79 PVs after loading) 3. Permanganate (45 PVs
Hydraulic fracturing system and method
Ciezobka, Jordan; Maity, Debotyam
2018-01-30
A hydraulic fracturing system and method for enhancing effective permeability of earth formations to increase hydrocarbon production, enhance operation efficiency by reducing fluid entry friction due to tortuosity and perforation, and to open perforations that are either unopened or not effective using traditional techniques, by varying a pump rate and/or a flow rate to a wellbore.
Hydraulic fracturing system and method
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ciezobka, Jordan; Maity, Debotyam
A hydraulic fracturing system and method for enhancing effective permeability of earth formations to increase hydrocarbon production, enhance operation efficiency by reducing fluid entry friction due to tortuosity and perforation, and to open perforations that are either unopened or not effective using traditional techniques, by varying a pump rate and/or a flow rate to a wellbore.
Zhang, Ding; Wang, Huai-Ji; Cui, Xiu-Ming; Wang, Cheng-Xiao
2017-06-01
In this work, imidazolium ionic liquids (imidazolium ILs) were employed as the novel chemical permeation enhancers (CPEs) and their performances and mechanisms of action were deeply investigated. Testosterone was used as a model drug to investigate the transdermal delivery enhancement of twenty imdidazolium ILs. The results suggested that the promotion activity connected to the structure and composition of the ILs. The quantitative structure-activity relationship (QSAR) model revealed a good linearity between the electronic properties of ILs and their enhancements. Furthermore, the transepidermal water loss (TEWL) and scanning laser confocal microscope (CLSM) examinations showed the strong improvement of ILs on skin barrier permeability, which were well correlated with the drug penetration profiles. The total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscope (AFM) evaluations of skins indicated that the ILs can disrupt the regular and compact arrangements of the corneocytes, change the surface properties of stratum corneum, and make the skin structure more permeable. Our work demonstrated the significant skin permeation promotion profiles of the imidazolium ILs, which are of great potential in transdermal drug delivery systems.
Tadalafil-loaded nanostructured lipid carriers using permeation enhancers.
Baek, Jong-Suep; Pham, Cuong Viet; Myung, Chang-Seon; Cho, Cheong-Weon
2015-11-30
Tadalafil is a phosphodiesterase-5 inhibitor indicated for the treatment of erectile dysfunction. In this study, we prepared and evaluated transdermal nanostructured lipid carriers (NLC) to improve the skin permeability of tadalafil. Tadalafil-loaded NLC dispersions were prepared using glyceryl monostearate as a solid lipid, oleic acid as a liquid lipid, and Tween 80 as a surfactant. We characterized the dispersions according to particle size, polydispersity index, zeta potential, encapsulation efficiency, and transmission electron microscopy. In vitro skin permeation studies were carried out using Franz diffusion cells, and cytotoxicity was examined using HaCaT keratinocyte cell lines. Tadalafil skin permeability increased for all tadalafil-loaded NLC formulations. The tadalafil-loaded NLC dispersion with ethanol and limonene as skin permeation enhancers exhibited the highest flux (∼4.8-fold) compared to that observed with tadalafil solution alone. Furthermore, a tadalafil-loaded NLC gel with selected permeation enhancers showed tolerance against toxicity in HaCaT cells. These results suggest that the NLC formulations with ethanol and limonene as skin permeation enhancers could be a promising dermal delivery carrier for tadalafil. Copyright © 2015 Elsevier B.V. All rights reserved.
Zhang, Kun; Li, Pei; He, Yaping; Bo, Xiaowan; Li, Xiaolong; Li, Dandan; Chen, Hangrong; Xu, Huixiong
2016-08-01
Despite gaining increasing attention, chelation of multiple active targeting ligands greatly increase the formation probability of protein corona, disabling active targeting. To overcome it, a synergistic retention strategy of RGD-mediated active targeting and radiofrequency (RF) electromagnetic field-enhanced permeability has been proposed here. It is validated that such a special synergistic retention strategy can promote more poly lactic-co-glycolic acid (PLGA)-based capsules encapsulating camptothecin (CPT) and solid DL-menthol (DLM) to enter and retain in tumor in vitro and in vivo upon exposure to RF irradiation, receiving an above 8 fold enhancement in HeLa retention. Moreover, the PLGA-based capsules can respond RF field to trigger the entrapped DLM to generate solid-liquid-gas (SLG) tri-phase transformation for enhancing RF ablation and CPT release. Therefore, depending on the enhanced RF ablation and released CPT and the validated synergistic retention effect, the inhibitory outcome for tumor growth has gained an over 10-fold improvement, realizing RF ablation & chemotherapy synergistic treatment against HeLa solid tumor, which indicates a significant promise in clinical RF ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Stevens, N. T.; Keranen, K. M.; Lambert, C.
2017-12-01
Recent earthquakes in north central Oklahoma are dominantly hosted on unmapped basement faults away from and outside of the largest regional structure, the Nemaha Fault Zone (NFZ) [Lambert, 2016]. The NFZ itself remains largely aseismic, despite the presence of disposal wells and numerous faults. Here we present results from double-difference tomography using TomoDD [Zhang and Thurber, 2003] for the NFZ and the surrounding region, utilizing a seismic catalog of over 10,000 local events acquired by 144 seismic stations deployed between 2013 and 2017. Inversion results for shallow crustal depth, beneath the 2-3 km sedimentary cover, show compressional wavespeeds (Vp) of >6 km/sec and shear wavespeeds (Vs) >4 km/sec outside the NFZ, consistent with crystalline rock. Along the western margin of the NFZ, both Vp and Vs are reduced, and Vp/Vs gradients parallel the trend of major faults, suggesting enhanced fault density and potentially enhanced fluid pressure within the study region. Enhanced fracture density within the NFZ, and associated permeability enhancement, could reduce the effect of regional fluid pressurization from injection wells, contributing to the relative aseismicity of the NFZ.
A computer program for simulating geohydrologic systems in three dimensions
Posson, D.R.; Hearne, G.A.; Tracy, J.V.; Frenzel, P.F.
1980-01-01
This document is directed toward individuals who wish to use a computer program to simulate ground-water flow in three dimensions. The strongly implicit procedure (SIP) numerical method is used to solve the set of simultaneous equations. New data processing techniques and program input and output options are emphasized. The quifer system to be modeled may be heterogeneous and anisotropic, and may include both artesian and water-table conditions. Systems which consist of well defined alternating layers of highly permeable and poorly permeable material may be represented by a sequence of equations for two dimensional flow in each of the highly permeable units. Boundaries where head or flux is user-specified may be irregularly shaped. The program also allows the user to represent streams as limited-source boundaries when the streamflow is small in relation to the hydraulic stress on the system. The data-processing techniques relating to ' cube ' input and output, to swapping of layers, to restarting of simulation, to free-format NAMELIST input, to the details of each sub-routine 's logic, and to the overlay program structure are discussed. The program is capable of processing large models that might overflow computer memories with conventional programs. Detailed instructions for selecting program options, for initializing the data arrays, for defining ' cube ' output lists and maps, and for plotting hydrographs of calculated and observed heads and/or drawdowns are provided. Output may be restricted to those nodes of particular interest, thereby reducing the volumes of printout for modelers, which may be critical when working at remote terminals. ' Cube ' input commands allow the modeler to set aquifer parameters and initialize the model with very few input records. Appendixes provide instructions to compile the program, definitions and cross-references for program variables, summary of the FLECS structured FORTRAN programming language, listings of the FLECS and FORTRAN source code, and samples of input and output for example simulations. (USGS)
NASA Astrophysics Data System (ADS)
Jia, W.; Pan, F.; McPherson, B. J. O. L.
2015-12-01
Due to the presence of multiple phases in a given system, CO2 sequestration with enhanced oil recovery (CO2-EOR) includes complex multiphase flow processes compared to CO2 sequestration in deep saline aquifers (no hydrocarbons). Two of the most important factors are three-phase relative permeability and hysteresis effects, both of which are difficult to measure and are usually represented by numerical interpolation models. The purposes of this study included quantification of impacts of different three-phase relative permeability models and hysteresis models on CO2 sequestration simulation results, and associated quantitative estimation of uncertainty. Four three-phase relative permeability models and three hysteresis models were applied to a model of an active CO2-EOR site, the SACROC unit located in western Texas. To eliminate possible bias of deterministic parameters on the evaluation, a sequential Gaussian simulation technique was utilized to generate 50 realizations to describe heterogeneity of porosity and permeability, initially obtained from well logs and seismic survey data. Simulation results of forecasted pressure distributions and CO2 storage suggest that (1) the choice of three-phase relative permeability model and hysteresis model have noticeable impacts on CO2 sequestration simulation results; (2) influences of both factors are observed in all 50 realizations; and (3) the specific choice of hysteresis model appears to be somewhat more important relative to the choice of three-phase relative permeability model in terms of model uncertainty.
Physiological barriers to the oral delivery of curcumin.
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.
Mechanisms of Visceral Organ Crosstalk: Importance of Alterations in Permeability in Rodent Models
Greenwood-Van Meerveld, B; Mohammadi, E; Tyler, K; Van Gordon, S; Parker, A; Towner, R; Hurst, R
2015-01-01
Purpose The pathophysiology of painful bladder syndrome (PBS) is poorly understood; however, there is evidence of female predominance and comorbidity with irritable bowel syndrome (IBS). Our hypothesis is that cross-sensitization between the bladder and colon is due to altered permeability in one organ affecting the other organ. Materials and methods Experiments were performed in anesthetized, ovariectomized (OVX) female rats. In separate groups, protamine sulfate was infused into the bladder or TNBS was infused into the colon, with untreated rats serving as controls. Both bladder and colonic tissue were harvested for all rats at 1, 3, and 5 days post-treatment. Permeability was assessed in vitro in Ussing chambers via measurements of transepithelial electrical resistance (TEER) and macromolecular flux of Fluorescein isothiocyanate (FITC)-4 dextran. Results Exposing the bladder to protamine sulfate induced a significant (p<0.05) decrease in bladder TEER and an increase in the translocation of FITC across the tissue compared to controls at 1 and 3 days. Colonic tissue from rats with enhanced bladder permeability exhibited a significant (p<0.05) decrease in TEER and increase in FITC when compared to untreated controls at all time points. Conversely, when colonic permeability was increased with TNBS, we observed an increase in bladder permeability in the absence of any changes to the bladder urothelium. Conclusions Changes in epithelial permeability may represent a novel mechanism for visceral organ crosstalk and may explain the overlapping symptomology of PBS and IBS. PMID:25776913
The effect of stress on limestone permeability and its effective stress behavior
NASA Astrophysics Data System (ADS)
Meng, F.; Baud, P.; Ge, H.; Wong, T. F.
2017-12-01
The evolution of permeability and its effective stress behavior is related to inelastic deformation and failure mode. This was investigated in Indiana and Purbeck limestones with porosities of 18% and 13%, respectively. Hydrostatic and triaxial compression tests were conducted at room temperature on water-saturated samples at pore pressure of 5 MPa and confining pressures up to 90 MPa. Permeability was measured using steady flow at different stages of deformation. For Indiana limestone, under hydrostatic loading pore collapse initiated at critical pressure P* 55 MPa with an accelerated reduction of permeability by 1/2. At a confinement of 35 MPa and above, shear-enhanced compaction initiated at critical stress C*, beyond which permeability reduction up to a factor of 3 was observed. At a confinement of 15 MPa and below, dilatancy initiated at critical stress C', beyond which permeability continued to decrease, with a negative correlation between porosity and permeability changes. Purbeck limestone showed similar evolution of permeability. Microstructural and mercury porosimetry data showed that pore size distribution in both Indiana and Purbeck limestones is bimodal, with significant proportions of macropores and micropores. The effective stress behaviour of a limestone with dual porosity is different from the prediction for a microscopically homogeneous assemblage, in that its effective stress coefficients for permeability and porosity change may attain values significantly >1. Indeed this was confirmed by our measurements (at confining pressures of 7-15 MPa and pore pressures of 1-3 MPa) in samples that had not been deformed inelastically. We also investigated the behavior in samples hydrostatically and triaxially compacted to beyond the critical stresses P* and C*, respectively. Experimental data for these samples consistently showed effective stress coefficients for both permeability and porosity change with values <1. Thus the effective stress behavior in an inelastically compacted sample is fundamentally different, with attributes akin to that of a microscopically homogeneous assemblage. This is likely related to compaction from pervasive collapse of macropores, which would effectively homogenize the initially bimodal pore size distribution.
Rinehart, Alex J.; Dewers, Thomas A.; Broome, Scott T.; ...
2016-08-25
We characterize geomechanical constitutive behavior of reservoir sandstones at conditions simulating the “Cranfield” Southeast Regional Carbon Sequestration Partnership injection program. From two cores of Lower Tuscaloosa Formation, three sandstone lithofacies were identified for mechanical testing based on permeability and lithology. These include: chlorite-cemented conglomeratic sandstone (Facies A); quartz-cemented fine sandstone (Facies B); and quartz- and calcite-cemented very fine sandstone (Facies C). We performed a suite of compression tests for each lithofacies at 100 °C and pore pressure of 30 MPa, including hydrostatic compression and triaxial tests at several confining pressures. Plugs were saturated with supercritical CO 2-saturated brine. Chemical environmentmore » affected the mechanical response of all three lithofacies, which experience initial plastic yielding at stresses far below estimated in situ stress. Measured elastic moduli degradation defines a secondary yield surface coinciding with in situ stress for Facies B and C. Facies A shows measurable volumetric creep strain and a failure envelope below estimates of in situ stress, linked to damage of chlorite cements by acidic pore solutions. Furthermore, the substantial weakening of a particular lithofacies by CO 2 demonstrates a possible chemical-mechanical coupling during injection at Cranfield with implications for CO 2 injection, reservoir permeability stimulation, and enhanced oil recovery.« less
Oil Recovery Enhancement from Fractured, Low Permeability Reservoirs. [Carbonated Water
DOE R&D Accomplishments Database
Poston, S. W.
1991-01-01
The results of the investigative efforts for this jointly funded DOE-State of Texas research project achieved during the 1990-1991 year may be summarized as follows: Geological Characterization - Detailed maps of the development and hierarchical nature the fracture system exhibited by Austin Chalk outcrops were prepared. The results of these efforts were directly applied to the development of production decline type curves applicable to a dual-fracture-matrix flow system. Analysis of production records obtained from Austin Chalk operators illustrated the utility of these type curves to determine relative fracture/matrix contributions and extent. Well-log response in Austin Chalk wells has been shown to be a reliable indicator of organic maturity. Shear-wave splitting concepts were used to estimate fracture orientations from Vertical Seismic Profile, VSP data. Several programs were written to facilitate analysis of the data. The results of these efforts indicated fractures could be detected with VSP seismic methods. Development of the EOR Imbibition Process - Laboratory displacement as well as Magnetic Resonance Imaging, MRI and Computed Tomography, CT imaging studies have shown the carbonated water-imbibition displacement process significantly accelerates and increases recovery from oil saturated, low permeability rocks. Field Tests - Two operators amenable to conducting a carbonated water flood test on an Austin Chalk well have been identified. Feasibility studies are presently underway.
NASA Astrophysics Data System (ADS)
Ohtsu, Naofumi; Kozuka, Taro; Shibata, Yuga; Yamane, Misao
2017-11-01
Plasma nitriding was explored for improving the thermal stability of a composite hydrogen permeable membrane comprising a Pd coating on Nb substrate. A NbN intermediate layer was formed on the Nb substrate, and the progress of interdiffusion and deterioration of hydrogen absorption behavior after a thermal treatment at 573 and 773 K, respectively, were investigated. The intermediate layer significantly suppressed the interdiffusion between the coating and the substrate. Furthermore, an increase in the NbN concentration of the intermediate layer enhanced the suppression efficiency. However, the hydrogen permeability of the intermediate layer was significantly low, and hence, an increase in NbN concentration further decreased the hydrogen permeability. We concluded that the nitride layer with a high NbN content was unsuitable as an intermediate layer owing to its low hydrogen permeability, while the partial nitride layer with a low NbN content was inefficient in suppressing the interdiffusion.
Mast cells and histamine alter intestinal permeability during malaria parasite infection.
Potts, Rashaun A; Tiffany, Caitlin M; Pakpour, Nazzy; Lokken, Kristen L; Tiffany, Connor R; Cheung, Kong; Tsolis, Renée M; Luckhart, Shirley
2016-03-01
Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection. Copyright © 2015 Elsevier GmbH. All rights reserved.
2014-10-01
enhanced amendments delivery process, a non-toxic biodegradable polymer, such as xanthan gum, is added to the injection solution to form a non- Newtonian...Once injection stops, the injected fluid viscosity increases and creates a more stable zone for biodegradation reactions because the amendment-laden...electron acceptors and biodegradation of the shear-thinning agent. • Determine the cost factors for applying the STF enhanced delivery technology
NASA Astrophysics Data System (ADS)
Carlino, Stefano; Piochi, Monica; Tramelli, Anna; Mormone, Angela; Montanaro, Cristian; Scheu, Bettina; Klaus, Mayer
2018-05-01
We report combined measurements of petrophysical and geophysical parameters for a 501-m deep borehole located on the eastern side of the active Campi Flegrei caldera (Southern Italy), namely (i) in situ permeability by pumping tests, (ii) laboratory-determined permeability of the drill core, and (iii) thermal gradients by distributed fiber optic and thermocouple sensors. The borehole was drilled during the Campi Flegrei Deep Drilling Project (in the framework of the International Continental Scientific Drilling Program) and gives information on the least explored caldera sector down to pre-caldera deposits. The results allow comparative assessment of permeability obtained from both borehole (at depth between 422 a 501 m) and laboratory tests (on a core sampled at the same depth) for permeability values of 10-13 m2 (borehole test) and 10-15 m2 (laboratory test) confirm the scale-dependency of permeability at this site. Additional geochemical and petrophysical determinations (porosity, density, chemistry, mineralogy and texture), together with gas flow measurements, corroborate the hypothesis that discrepancies in the permeability values are likely related to in-situ fracturing. The continuous distributed temperature profile points to a thermal gradient of about 200 °C km-1. Our findings (i) indicate that scale-dependency of permeability has to be carefully considered in modelling of the hydrothermal system at Campi Flegrei, and (ii) improve the understanding of caldera dynamics for monitoring and mitigation of this very high volcanic risk area.
Permeability of sediment cores from methane hydrate deposit in the Eastern Nankai Trough, Japan
NASA Astrophysics Data System (ADS)
Konno, Y.; Yoneda, J.; Egawa, K.; Ito, T.; Jin, Y.; Kida, M.; Suzuki, K.; Nakatsuka, Y.; Nagao, J.
2013-12-01
Effective and absolute permeability are key parameters for gas production from methane-hydrate-bearing sandy sediments. Effective and/or absolute permeability have been measured using methane-hydrate-bearing sandy cores and clayey and silty cores recovered from Daini Atsumi Knoll in the Eastern Nankai Trough during the 2012 JOGMEC/JAPEX Pressure coring operation. Liquid-nitrogen-immersed cores were prepared by rapid depressurization of pressure cores recovered by a pressure coring system referred to as the Hybrid PCS. Cores were shaped cylindrically on a lathe with spraying of liquid nitrogen to prevent hydrate dissociation. Permeability was measured by a flooding test or a pressure relaxation method under near in-situ pressure and temperature conditions. Measured effective permeability of hydrate-bearing sediments is less than tens of md, which are order of magnitude less than absolute permeability. Absolute permeability of clayey cores is approximately tens of μd, which would perform a sealing function as cap rocks. Permeability reduction due to a swelling effect was observed for a silty core during flooding test of pure water mimicking hydrate-dissociation-water. Swelling effect may cause production formation damage especially at a later stage of gas production from methane hydrate deposits. This study was financially supported by the Research Consortium for Methane Hydrate Resources in Japan (MH21 Research Consortium) that carries out Japan's Methane Hydrate R&D Program conducted by the Ministry of Economy, Trade and Industry (METI).
Injectivity Evaluation for Offshore CO 2 Sequestration in Marine Sediments
Dai, Zhenxue; Zhang, Ye; Stauffer, Philip; ...
2017-08-18
Global and regional climate change caused by greenhouse gases emissions has stimulated interest in developing various technologies (such as carbon dioxide (CO 2) geologic sequestration in brine reservoirs) to reduce the concentrations of CO 2 in the atmosphere. Our study develops a statistical framework to identify gravitational CO 2 trapping processes and to quantitatively evaluate both CO 2 injectivity (or storage capacity) and leakage potential from marine sediments which exhibit heterogeneous permeability and variable thicknesses. Here, we focus on sets of geostatistically-based heterogeneous models populated with fluid flow parameters from several reservoir sites in the U.S. Gulf of Mexico (GOM).more » A computationally efficient uncertainty quantification study was conducted with results suggesting that permeability heterogeneity and anisotropy, seawater depth, and sediment thickness can all significantly impact CO 2 flow and trapping. Large permeability/porosity heterogeneity can enhance gravitational, capillary, and dissolution trapping, which acts to deter CO 2 upward migration and subsequent leakage onto the seafloor. When log permeability variance is 5, self-sealing with heterogeneity-enhanced gravitation trapping can be achieved even when water depth is 1.2 km. This extends the previously identified self-sealing condition that water depth be greater than 2.7 km. Our results have yielded valuable insight into the conditions under which safe storage of CO 2 can be achieved in offshore environments. The developed statistical framework is general and can be adapted to study other offshore sites worldwide.« less
Injectivity Evaluation for Offshore CO 2 Sequestration in Marine Sediments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dai, Zhenxue; Zhang, Ye; Stauffer, Philip
Global and regional climate change caused by greenhouse gases emissions has stimulated interest in developing various technologies (such as carbon dioxide (CO 2) geologic sequestration in brine reservoirs) to reduce the concentrations of CO 2 in the atmosphere. Our study develops a statistical framework to identify gravitational CO 2 trapping processes and to quantitatively evaluate both CO 2 injectivity (or storage capacity) and leakage potential from marine sediments which exhibit heterogeneous permeability and variable thicknesses. Here, we focus on sets of geostatistically-based heterogeneous models populated with fluid flow parameters from several reservoir sites in the U.S. Gulf of Mexico (GOM).more » A computationally efficient uncertainty quantification study was conducted with results suggesting that permeability heterogeneity and anisotropy, seawater depth, and sediment thickness can all significantly impact CO 2 flow and trapping. Large permeability/porosity heterogeneity can enhance gravitational, capillary, and dissolution trapping, which acts to deter CO 2 upward migration and subsequent leakage onto the seafloor. When log permeability variance is 5, self-sealing with heterogeneity-enhanced gravitation trapping can be achieved even when water depth is 1.2 km. This extends the previously identified self-sealing condition that water depth be greater than 2.7 km. Our results have yielded valuable insight into the conditions under which safe storage of CO 2 can be achieved in offshore environments. The developed statistical framework is general and can be adapted to study other offshore sites worldwide.« less
Hüve, Katja; Bichele, Irina; Rasulov, Bahtijor; Niinemets, Ulo
2011-01-01
Photosynthesis rate (A(n)) becomes unstable above a threshold temperature, and the recovery upon return to low temperature varies because of reasons not fully understood. We investigated responses of A(n), dark respiration and chlorophyll fluorescence to supraoptimal temperatures of varying duration and kinetics in Phaseolus vulgaris asking whether the instability of photosynthesis under severe heat stress is associated with cellular damage. Cellular damage was assessed by Evans blue penetration (enhanced membrane permeability) and by H₂O₂ generation [3,3'-diaminobenzidine 4HCl (DAB)-staining]. Critical temperature for dark fluorescence (F(0) ) rise (T(F)) was at 46-48 °C, and a burst of respiration was observed near T(F). However, A(n) was strongly inhibited already before T(F) was reached. Membrane permeability increased with temperature according to a switch-type response, with enhanced permeability observed above 48 °C. Experiments with varying heat pulse lengths and intensities underscored the threshold-type loss of photosynthetic function, and indicated that the degree of photosynthetic deterioration and cellular damage depended on accumulated heat-dose. Beyond the 'point of no return', propagation of cellular damage and reduction of photosynthesis continued upon transfer to lower temperatures and photosynthetic recovery was slow or absent. We conclude that instability of photosynthesis under severe heat stress is associated with time-dependent propagation of cellular lesions. © 2010 Blackwell Publishing Ltd.
Zhang, Xiaolin; Jiang, Anmin; Yu, Hao; Xiong, Youyi; Zhou, Guoliang; Qin, Meisong; Dou, Jinfeng; Wang, Jianfei
2016-10-28
Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori ( H. pylori ). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1- N -phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori . Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori , and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.
Zhao, Shulan; Lian, Fei; Duo, Lian
2011-01-01
A column experiment with horizontal permeable barriers was conducted to investigate phytoextraction of heavy metals by Lolium perenne L. from municipal solid waste compost following EDTA application, as well as to study the effects of L. perenne and permeable barriers on preventing metal from leaching. In columns with barriers, EDTA addition yielded maximum concentrations of Cu, Zn and Pb of 155, 541 and 33.5 mg kg(-1) in shoot, respectively. This led to 4.2, 2.1 and 7.4 times higher concentrations of Cu, Zn and Pb compared to treatment with no chelating agent, respectively. In treatments with 10 mmol kg(-1) EDTA, the barriers reduced leaching of Cu, Zn and Pb by approximately three times, respectively, resulting in leaching of total initial Cu, Zn and Pb by 27.3%, 25.2% and 28.8%, respectively, after four times' irrigation. These results indicate that L. perenne and permeable barriers are effective to reduce leaching of heavy metals and minimize the risk of contaminating groundwater in EDTA-enhanced phytoremediation. Thus these findings highlight that turfgrass and permeable barriers can effectively prevent metal leaching. Copyright © 2010 Elsevier Ltd. All rights reserved.
Gundogdu, E; Gonzalez Alvarez, I; Bermejo Sanz, M; Karasulu, E
2011-10-01
The purpose of this study was to estimate the effect of the anionic surfactant sodium dodecyl sulphate (SDS) on the permeability and dissolution of fexofenadine hydrochloride (FEX) and the transepithelial electrical resistance (TEER) with Caco-2 cells. The dissolution profile of FEX was evaluated at different pH values (1.2, 3.2, 4.2, 4.5, 5.2 and 6.8) at 37 +/- 0.5 degrees C and chracterized in presence of SDS. The dissolution of FEX was increased in the presence of SDS. For permeability studies, apical to basolateral and basolateral to apical permeability was assesed with various concentrations of FEX (50, 100, 500, 1000 and 5000 microM) and in the presence of SDS. The FEX transport changed with 10 and 50 microM of SDS and the TEER values, after 120 min, decreased. In conclusion, a low and concentration-dependent permeability was found for FEX across the Caco-2 cells. FEX transport increased and TEER decreased with increasing SDS concentrations. These results supports the use of SDS as anionic surfactant in these concentration; SDS can be used safely as permeation and dissolution enhancer for the oral delivery of FEX.
Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho
2017-08-08
Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.
Haine, Aung Thu; Koga, Yuki; Hashimoto, Yuta; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi; Niidome, Takuro
2017-10-01
Transdermal protein delivery is a useful and attractive method for protein therapy and dermal vaccination. However, this delivery method is restricted by the low permeability of the stratum corneum. The purpose of this study was to develop a transdermal delivery system for enhancement of protein permeability into the skin. First, we prepared a transparent gel patch made of polysaccharides with gold nanorods on the gel surface and fluorescein isothiocyanate-modified ovalbumin (FITC-OVA) inside. Next, the gel patch was placed on mouse skin to allow contact with the coated gold nanorods, and irradiated by a continuous-wave laser. The laser irradiation heated the gold nanorods and the skin temperature increased to 43°C, resulting in enhanced translocation of FITC-OVA into the skin. These results confirmed the capability of the transdermal protein delivery system to perforate the stratum corneum and thus facilitate the passage of proteins across the skin. Copyright © 2017 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Zabner, Joseph; Seiler, Michael P.; Launspach, Janice L.; Karp, Philip H.; Kearney, William R.; Look, Dwight C.; Smith, Jeffrey J.; Welsh, Michael J.
2000-10-01
The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.
Qhattal, Hussaini Syed Sha; Wang, Shu; Salihima, Tri; Srivastava, Sanjay K; Liu, Xinli
2011-12-14
Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, is an effective chemopreventive agent. The objective of this study was to develop nanoemulsion formulations for the oral delivery of BITC. Optimized oil-in-water BITC nanoemulsions were prepared by a spontaneous self-nanoemulsification method and a homogenization-sonication method. Both nanoemulsions entrapped high amounts of BITC (15-17 mg/mL), with low polydispersity and good colloidal stability. The BITC nanoemulsions showed enhanced solubility and dissolution compared to pure BITC. These formulations markedly increased the apical to basolateral transport of BITC in Caco-2 cell monolayers. The apparent permeability values were 3.6 × 10(-6) cm/s for pure BITC and (1.1-1.3) × 10(-5) cm/s for BITC nanoemulsions. The nanoemulsions were easily taken up by human cancer cells A549 and SKOV-3 and inhibited tumor growth in vitro. This work shows for the first time that BITC can be formulated into nanoemulsions and may show promise in enhancing absorption and bioavailability.
Wu, Juyou; Wang, Su; Gu, Yuchun; Zhang, Shaoling; Publicover, Stephen J.; Franklin-Tong, Vernonica E.
2011-01-01
Cellular responses rely on signaling. In plant cells, cytosolic free calcium is a major second messenger, and ion channels play a key role in mediating physiological responses. Self-incompatibility (SI) is an important genetically controlled mechanism to prevent self-fertilization. It uses interaction of matching S-determinants from the pistil and pollen to allow “self” recognition, which triggers rejection of incompatible pollen. In Papaver rhoeas, the S-determinants are PrsS and PrpS. PrsS is a small novel cysteine-rich protein; PrpS is a small novel transmembrane protein. Interaction of PrsS with incompatible pollen stimulates S-specific increases in cytosolic free calcium and alterations in the actin cytoskeleton, resulting in programmed cell death in incompatible but not compatible pollen. Here, we have used whole-cell patch clamping of pollen protoplasts to show that PrsS stimulates SI-specific activation of pollen grain plasma membrane conductance in incompatible but not compatible pollen grain protoplasts. The SI-activated conductance does not require voltage activation, but it is voltage sensitive. It is permeable to divalent cations (Ba2+ ≥ Ca2+ > Mg2+) and the monovalent ions K+ and NH4+ and is enhanced at voltages negative to −100 mV. The Ca2+ conductance is blocked by La3+ but not by verapamil; the K+ currents are tetraethylammonium chloride insensitive and do not require Ca2+. We propose that the SI-stimulated conductance may represent a nonspecific cation channel or possibly two conductances, permeable to monovalent and divalent cations. Our data provide insights into signal-response coupling involving a biologically important response. PrsS provides a rare example of a protein triggering alterations in ion channel activity. PMID:21177472
Geomechanical Response of Jointed Caprock During CO2 Geological Sequestration
NASA Astrophysics Data System (ADS)
Newell, P.; Martinez, M. J.; Bishop, J. E.
2014-12-01
Geological sequestration of CO2 refers to the injection of supercritical CO2 into deep reservoirs trapped beneath a low-permeability caprock formation. Maintaining caprock integrity during the injection process is the most important factor for a successful injection. In this work we evaluate the potential for jointed caprock during injection scenarios using coupled three-dimensional multiphase flow and geomechanics modeling. Evaluation of jointed/fractured caprock systems is of particular concern to CO2 sequestration because creation or reactivation of joints (mechanical damage) can lead to enhanced pathways for leakage. In this work, we use an equivalent continuum approach to account for the joints within the caprock. Joint's aperture and non-linear stiffness of the caprock will be updated dynamically based on the effective normal stress. Effective permeability field will be updated based on the joints' aperture creating an anisotropic permeability field throughout the caprock. This feature would add another coupling between the solid and fluid in addition to basic Terzaghi's effective stress concept. In this study, we evaluate the impact of the joint's orientation and geometry of caprock and reservoir layers on geomechanical response of the CO2 geological systems. This work is supported as part of the Center for Frontiers of Subsurface Energy Security, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Award Number DE-SC0001114. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.
NASA Astrophysics Data System (ADS)
Sitthiwet, Chongsutthamani; Thiangviriya, Sophida; Thaweelap, Natthaporn; Meethom, Sukanya; Kaewsuwan, Dechmongkhon; Chanlek, Narong; Utke, Rapee
2017-11-01
Activated carbon nanofibers impregnated with titanium (IV) oxide (TiO2), denoted as ACNF-Ti are prepared by carbonization and activation of electrospun nanofibers of polyacrylonitrile (PAN)-titanium (IV) isopropoxide composite. Pristine LiBH4 and nanoconfined LiBH4 in ACNF-Ti, denoted as LiBH4-ACNF-Ti are compacted under the pressures of 434 and 868 MPa. Dehydrogenation temperature of compacted LiBH4 increases (up to 485 °C) with compaction pressure due to poor hydrogen permeability. In the case of compacted LiBH4-ACNF-Ti, major dehydrogenation temperature at 352-359 °C and hydrogen content liberated (74-76% of theoretical capacity) are obtained despite enhanced compaction pressure. Mechanical stability during cycling of compacted LiBH4-ACNF-Ti is achieved. Although hydrogen permeability of compacted LiBH4-ACNF-Ti improves with enhanced compaction pressure, detrimental kinetics and reversibility are detected. Since the fibrous structure of ACNF-Ti are brittle, the broken and/or shorten fibers are observed after compaction under high pressure. The latter results in not only inferior nanoconfinement of LiBH4 into ACNF-Ti, but also agglomeration of hydride materials upon cycling.
Environmental Electrokinetics for a sustainable subsurface.
Lima, A T; Hofmann, A; Reynolds, D; Ptacek, C J; Van Cappellen, P; Ottosen, L M; Pamukcu, S; Alshawabekh, A; O'Carroll, D M; Riis, C; Cox, E; Gent, D B; Landis, R; Wang, J; Chowdhury, A I A; Secord, E L; Sanchez-Hachair, A
2017-08-01
Soil and groundwater are key components in the sustainable management of the subsurface environment. Source contamination is one of its main threats and is commonly addressed using established remediation techniques such as in-situ chemical oxidation (ISCO), in-situ chemical reduction (ISCR; most notably using zero-valent iron [ZVI]), enhanced in-situ bioremediation (EISB), phytoremediation, soil-washing, pump-and-treat, soil vapour extraction (SVE), thermal treatment, and excavation and disposal. Decades of field applications have shown that these techniques can successfully treat or control contaminants in higher permeability subsurface materials such as sands, but achieve only limited success at sites where low permeability soils, such as silts and clays, prevail. Electrokinetics (EK), a soil remediation technique mostly recognized in in-situ treatment of low permeability soils, has, for the last decade, been combined with more conventional techniques and can significantly enhance the performance of several of these remediation technologies, including ISCO, ISCR, EISB and phytoremediation. Herein, we discuss the use of emerging EK techniques in tandem with conventional remediation techniques, to achieve improved remediation performance. Furthermore, we highlight new EK applications that may come to play a role in the sustainable treatment of the contaminated subsurface. Copyright © 2017 Elsevier Ltd. All rights reserved.
Transdermal delivery of paeonol using cubic gel and microemulsion gel
Luo, Maofu; Shen, Qi; Chen, Jinjin
2011-01-01
Background The aim of this study was to develop new systems for transdermal delivery of paeonol, in particular microemulsion gel and cubic gel formulations. Methods Various microemulsion vehicles were prepared using isopropyl myristate as an oil phase, polyoxyethylated castor oil (Cremophor® EL) as a surfactant, and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel formulation, carbomer 940 was selected as the gel matrix, and consisted of 1% paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1), and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and 67% glyceryl monooleate. Results A skin permeability test using excised rat skins indicated that both the cubic gel and microemulsion gel formulations had higher permeability than did the paeonol solution. An in vivo pharmacokinetic study done in rats showed that the relative bioavailability of the cubic gel and microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively, compared with orally administered paeonol suspension. Conclusion Both the cubic gel and microemulsion gel formulations are promising delivery systems to enhance the skin permeability of paeonol, in particular the cubic gel. PMID:21904450
Bergamino, M; Bonzano, L; Levrero, F; Mancardi, G L; Roccatagliata, L
2014-09-01
In the last few years, several imaging methods, such as magnetic resonance imaging (MRI) and computed tomography, have been used to investigate the degree of blood-brain barrier (BBB) permeability in patients with neurological diseases including multiple sclerosis, ischemic stroke, and brain tumors. One promising MRI method for assessing the BBB permeability of patients with neurological diseases in vivo is T1-weighted dynamic contrast-enhanced (DCE)-MRI. Here we review the technical issues involved in DCE-MRI in the study of human brain tumors. In the first part of this paper, theoretical models for the DCE-MRI analysis will be described, including the Toft-Kety models, the adiabatic approximation to the tissue homogeneity model and the two-compartment exchange model. These models can be used to estimate important kinetic parameters related to BBB permeability. In the second part of this paper, details of the data acquisition, issues related to the arterial input function, and procedures for DCE-MRI image analysis are illustrated. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Diffusion of Chlorinated Organic Contaminants into Aquitards: Enhanced by the Flocculation of Clay?
NASA Astrophysics Data System (ADS)
Ayral, D.; Otero, M.; Demond, A. H.; Goltz, M. N.; Huang, J.
2011-12-01
Waste organic contaminants stored in low permeability subsurface layers serve as long-term sources for dissolved phase contaminant plumes. Current models consider the movement into and out of aquitards or other low permeability layers to occur through transverse diffusion. Yet, field evidence suggests higher transport rates of contaminants than can be accounted for by diffusion alone. Waste organic liquids contain both organic liquid solvents as well as surface-active solutes. Measurements using montmorillonite in contact with pure chlorinated organic liquids such as trichloroethylene (TCE) showed that the basal spacing is similar to the case of montmorillonite in contact with air, thus suggesting that these fluids have similar flocculation effects. On the other hand, the basal spacing increased in contact with aqueous surfactant solutions. Measurements of the basal spacing in contact with a TCE waste gave the same results as with pure TCE, suggesting that effect on basal spacing is dominated by the organic solvent matrix rather than by the surfactant content. Since flocculation can lead to cracking, this behavior suggests that aquitards underlying aquifers contaminated with chlorinated organic wastes may develop cracks, thus enhancing the transport into low permeability layers.
Inferring Firn Permeability from Pneumatic Testing: A Case Study on the Greenland Ice Sheet
NASA Astrophysics Data System (ADS)
Sommers, Aleah N.; Rajaram, Harihar; Weber, Eliezer P.; MacFerrin, Michael J.; Colgan, William T.; Stevens, C. Max
2017-03-01
Across the accumulation zone of the Greenland ice sheet, summer temperatures can be sufficiently warm to cause widespread melting, as was the case in July 2012 when the entire ice sheet experienced a brief episode of enhanced surface ablation. The resulting meltwater percolates into the firn and refreezes, to create ice lenses and layers within the firn column. This is an important process to consider when estimating the surface mass balance of the ice sheet. The rate of meltwater percolation depends on the permeability of the firn, a property that is not well constrained in the presence of refrozen ice layers and lenses. We present a novel, inexpensive method for measuring in-situ firn permeability using pneumatic testing, a well-established technique used in environmental engineering and hydrology. To illustrate the capabilities of this method, we estimate both horizontal and vertical permeability from pilot tests at six sites on the Greenland ice sheet: KAN-U, DYE-2, EKT, NASA-SE, Saddle, and EastGRIP. These sites cover a range of conditions from mostly dry firn (EastGRIP), to firn with several ice layers and lenses from refrozen meltwater (Saddle, NASA-SE, EKT), to firn with extensive ice layers (DYE-2 and KAN-U). The estimated permeability in firn without refrozen ice layers at EastGRIP agrees well with the range previously reported using an air permeameter to measure permeability through firn core samples at Summit, Greenland. At sites with ice lenses or layers, we find high degrees of anisotropy, with vertical permeability much lower than horizontal permeability. Pneumatic testing is a promising and low-cost technique for measuring firn permeability, particularly as meltwater production increases in the accumulation zone and ice layers and lenses from refrozen melt layers become more prevalent. In these initial proof-of-concept tests, the estimated permeabilities represent effective permeability at the meter scale. With appropriately higher vacuum pressures and more detailed monitoring, effective permeabilities over a larger scale may be quantified reliably, and multiple measurements during a season and across multiple years could improve understanding of the evolving firn structure and permeability. The technique is also suitable for broad application in Antarctica and other glaciers and ice caps.
Lehnert, B E; Archuleta, D; Gurley, L R; Session, W; Behr, M J; Lehnert, N M; Stavert, D M
1995-01-01
Exercise performed after exposure to various pneumoedematogenic gases can increase the severity of pulmonary edema beyond that which occurs when exposure is followed by rest. The present study was performed to investigate the potential relationship between a preexisting breach in the lung's permeability status following exposure to an edematogenic gas (perfluoroisobutylene, PFIB) and the potentiating effects of postexposure exercise. Rats were exposed to a concentration of PFIB (100 mg/M3 for 10 min) that results in a unique postexposure latency period (approximately 8 h) prior to the occurrence of overt pulmonary edema. The study examined how exercise performed during and after the latency period affects the severity of the injurious response to this toxic gas. The initial results indicated that exercise performed during the post-PFIB exposure latency period does not potentiate the injurious response, as judged by conventional lung gravimetric and histopathological criteria, but when overt pulmonary edema was preexistent, exercise had a potentiating effect. Changes in lavageable protein were assessed as a more sensitive indicator of permeability changes that may occur during the latency period following PFIB exposure, and the study examined how exercise performed early during the latency period affects this index of pulmonary edema. The study also assessed whether PFIB-induced damage to lung cells is enhanced by exercise during the latency period by measuring lavageable lactate dehydrogenase activity. The results from these latter experiments suggest that a preexisting enhancement in lung permeability is not an absolute requirement for exercise to potentiate the pulmonary edematous response in lungs that are undergoing insidious injury, and that postexposure exercise does not enhance the cell-killing effects of PFIB as a mechanism underlying the exercise potentiating response. Conceivably, the ability of exercise to increase lavageable protein in the absence of a preexisting increase in lung permeability may be due to hyperventilation- and/or pulmonary hypertension-associated intercellular junctional changes that may occur during exercise. Additionally, it remains possible that exercise during PFIB-induced insideous lung injury results in an enhancement in the rate of transcellular transport of blood proteins onto the alveolar surface.
Effects of capillary heterogeneity on vapor-liquid counterflow in porous media
NASA Astrophysics Data System (ADS)
Stubos, A. K.; Satik, C.; Yortsos, Y. C.
1992-06-01
Based on a continuum description, the effect of capillary heterogeneity, induced by variation in permeability, on the steady state, countercurrent, vapor-liquid flow in porous media is analyzed. It is shown that the heterogeneity acts as a body force that may enhance or diminish gravity effects on heat pipes. Selection rules that determine the steady states reached in homogeneous, gravity-driven heat pipes are also formulated. It is shown that the 'infinite' two-phase zone may terminate by a substantial change in the permeability somewhere in the medium. The two possible sequences, liquid-liquid dominated-dry, or liquid-vapor dominated-dry find applications in geothermal systems. Finally, it is shown that although weak heterogeneity affects only gravity controlled flows, stronger variations in permeability can give rise to significant capillary effects.
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
Fault Damage Zone Permeability in Crystalline Rocks from Combined Field and Laboratory Measurements
NASA Astrophysics Data System (ADS)
Mitchell, T.; Faulkner, D.
2008-12-01
In nature, permeability is enhanced in the damage zone of faults, where fracturing occurs on a wide range of scales. Here we analyze the contribution of microfracture damage on the permeability of faults that cut through low porosity, crystalline rocks by combining field and laboratory measurements. Microfracture densities surrounding strike-slip faults with well-constrained displacements ranging over 3 orders of magnitude (~0.12 m - 5000 m) have been analyzed. The faults studied are excellently exposed within the Atacama Fault Zone, where exhumation from 6-10 km has occurred. Microfractures in the form of fluid inclusion planes (FIPs) show a log-linear decrease in fracture density with perpendicular distance from the fault core. Damage zone widths defined by the density of FIPs scale with fault displacement, and an empirical relationship for microfracture density distribution throughout the damage zone with displacement is derived. Damage zone rocks will have experienced differential stresses that were less than, but some proportion of, the failure stress. As such, permeability data from progressively loaded, initially intact laboratory samples, in the pre-failure region provide useful insights into fluid flow properties of various parts of the damage zone. The permeability evolution of initially intact crystalline rocks under increasing differential load leading to macroscopic failure was determined at water pore pressures of 50 MPa and effective pressure of 10 MPa. Permeability is seen to increase by up to, and over, two orders of magnitude prior to macroscopic failure. Further experiments were stopped at various points in the loading history in order to correlate microfracture density within the samples with permeability. By combining empirical relationships determined from both quantitative fieldwork and experiments we present a model that allows microfracture permeability distribution throughout the damage zone to be determined as function of increasing fault displacement.
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.
Kuo, Yung-Chih; Kuo, Chan-Ying
2008-03-03
Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN>PBCA>MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases.
Transporter targeted gatifloxacin prodrugs: synthesis, permeability, and topical ocular delivery.
Vooturi, Sunil K; Kadam, Rajendra S; Kompella, Uday B
2012-11-05
In this work, we aim to design and synthesize prodrugs of gatifloxacin targeting organic cation transporter (OCT), monocarboxylate transporter (MCT), and ATB (0, +) transporters and to identify a prodrug with enhanced delivery to the back of the eye. Dimethylamino-propyl, carboxy-propyl, and amino-propyl(2-methyl) derivatives of gatifloxacin (GFX), DMAP-GFX, CP-GFX, and APM-GFX, were designed and synthesized to target OCT, MCT, and ATB (0, +) transporters, respectively. An LC-MS method was developed to analyze drug and prodrug levels in various studies. Solubility and log D (pH 7.4) were measured for prodrugs and the parent drug. The permeability of the prodrugs was determined in the cornea, conjunctiva, and sclera-choroid-retinal pigment epitheluim (SCRPE) and compared with gatifloxacin using an Ussing chamber assembly. Permeability mechanisms were elucidated by determining the transport in the presence of transporter specific inhibitors. 1-Methyl-4-phenylpyridinium iodide (MPP+), nicotinic acid sodium salt, and α-methyl-DL-tryptophan were used to inhibit OCT, MCT, and ATB (0, +) transporters, respectively. A prodrug selected based on in vitro studies was administered as an eye drop to pigmented rabbits, and the delivery to various eye tissues including vitreous humor was compared with gatifloxacin dosing. DMAP-GFX exhibited 12.8-fold greater solubility than GFX. All prodrugs were more lipophilic, with the measured log D (pH 7.4) values ranging from 0.05 to 1.04, when compared to GFX (log D: -1.15). DMAP-GFX showed 1.4-, 1.8-, and 1.9-fold improvement in permeability across the cornea, conjunctiva, and SCRPE when compared to GFX. Moreover, it exhibited reduced permeability in the presence of MPP+ (competitive inhibitor of OCT), indicating OCT-mediated transport. CP-GFX showed 1.2-, 2.3-, and 2.5-fold improvement in permeability across the cornea, conjunctiva, and SCRPE, respectively. In the presence of nicotinic acid (competitive inhibitor of MCT), the permeability of CP-GFX was reduced across the conjunctiva. However, the cornea and SCRPE permeability of CP-GFX was not affected by nicotinic acid. APM-GFX did not show any improvement in permeability when compared to GFX across the cornea, conjunctiva, and SCRPE. Based on solubility and permeability, DMAP-GFX was selected for in vivo studies. DMAP-GFX showed 3.6- and 1.95-fold higher levels in vitreous humor and CRPE compared to that of GFX at 1 h after topical dosing. In vivo conversion of DMAP-GFX prodrug to GFX was quantified in tissues isolated at 1 h after dosing. The parent drug-to-prodrug ratio was 8, 70, 24, 21, 29, 13, 55, and 60% in the cornea, conjunctiva, iris-ciliary body, aqueous humor, sclera, CRPE, retina, and vitreous humor, respectively. In conclusion, DMAP-GFX prodrug enhanced solubility, log D, as well as OCT mediated delivery of gatifloxacin to the back of the eye.
Airfoil-shaped micro-mixers for reducing fouling on membrane surfaces
Ho, Clifford K; Altman, Susan J; Clem, Paul G; Hibbs, Michael; Cook, Adam W
2012-10-23
An array of airfoil-shaped micro-mixers that enhances fluid mixing within permeable membrane channels, such as used in reverse-osmosis filtration units, while minimizing additional pressure drop. The enhanced mixing reduces fouling of the membrane surfaces. The airfoil-shaped micro-mixer can also be coated with or comprised of biofouling-resistant (biocidal/germicidal) ingredients.
Smith, Megan M.; Hao, Y.; Carroll, S. A.
2017-01-02
Here, beneficial pore space and permeability enhancements are likely to occur as CO 2-charged fluids partially dissolve carbonate minerals in carbonate reservoir formations used for geologic CO 2 storage. The ability to forecast the extent and impact of changes in porosity and permeability will aid geologic CO 2 storage operations and lower uncertainty in estimates of long-term storage capacity. Our work is directed toward developing calibrated reactive transport models that more accurately capture the chemical impacts of CO 2-fluid-rock interactions and their effects on porosity and permeability by matching pressure, fluid chemistry, and dissolution features that developed as a resultmore » of reaction with CO 2-acidified brines at representative reservoir conditions. We present new results from experiments conducted on seven core samples from the Arbuckle Dolostone (near Wellington, Kansas, USA, recovered as part of the South-Central Kansas CO 2 Demonstration). Cores were obtained from both target reservoir and lower-permeability baffle zones, and together these samples span over 3–4 orders of magnitude of permeability according to downhole measurements. Core samples were nondestructively imaged by X-ray computed tomography and the resulting characterization data were mapped onto a continuum domain to further develop a reactive transport model for a range of mineral and physical heterogeneity. We combine these new results with those from previous experimental studies to more fully constrain the governing equations used in reactive transport models to better estimate the transition of enhanced oil recovery operations to long-term geology CO 2 storage. Calcite and dolomite kinetic rate constants (mol m –2 s –1) derived by fitting the results from core-flood experiments range from k calcite,25C = 10 –6.8 to 10 –4.6, and k dolomite,25C = 10 –7.5 to 10 –5.3. The power law-based porosity-permeability relationship is sensitive to the overall pore space heterogeneity of each core. Stable dissolution fronts observed in the more homogeneous dolostones could be accurately simulated using an exponential value of n = 3. Furthermore, unstable dissolution fronts consisting of preferential flowpaths could be simulated using an exponential value of n = 3 for heterogeneous dolostones, and larger values ( n = 6–8) for heterogeneous limestones.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Smith, Megan M.; Hao, Y.; Carroll, S. A.
Here, beneficial pore space and permeability enhancements are likely to occur as CO 2-charged fluids partially dissolve carbonate minerals in carbonate reservoir formations used for geologic CO 2 storage. The ability to forecast the extent and impact of changes in porosity and permeability will aid geologic CO 2 storage operations and lower uncertainty in estimates of long-term storage capacity. Our work is directed toward developing calibrated reactive transport models that more accurately capture the chemical impacts of CO 2-fluid-rock interactions and their effects on porosity and permeability by matching pressure, fluid chemistry, and dissolution features that developed as a resultmore » of reaction with CO 2-acidified brines at representative reservoir conditions. We present new results from experiments conducted on seven core samples from the Arbuckle Dolostone (near Wellington, Kansas, USA, recovered as part of the South-Central Kansas CO 2 Demonstration). Cores were obtained from both target reservoir and lower-permeability baffle zones, and together these samples span over 3–4 orders of magnitude of permeability according to downhole measurements. Core samples were nondestructively imaged by X-ray computed tomography and the resulting characterization data were mapped onto a continuum domain to further develop a reactive transport model for a range of mineral and physical heterogeneity. We combine these new results with those from previous experimental studies to more fully constrain the governing equations used in reactive transport models to better estimate the transition of enhanced oil recovery operations to long-term geology CO 2 storage. Calcite and dolomite kinetic rate constants (mol m –2 s –1) derived by fitting the results from core-flood experiments range from k calcite,25C = 10 –6.8 to 10 –4.6, and k dolomite,25C = 10 –7.5 to 10 –5.3. The power law-based porosity-permeability relationship is sensitive to the overall pore space heterogeneity of each core. Stable dissolution fronts observed in the more homogeneous dolostones could be accurately simulated using an exponential value of n = 3. Furthermore, unstable dissolution fronts consisting of preferential flowpaths could be simulated using an exponential value of n = 3 for heterogeneous dolostones, and larger values ( n = 6–8) for heterogeneous limestones.« less
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.
Investigation of the feasibility of developing low permeability polymeric films
NASA Technical Reports Server (NTRS)
Hoggatt, J. T.
1971-01-01
The feasibility of reducing the gas permeability rate of Mylar and Kapton films without drastically effecting their flexibility characteristics at cryogenic temperatures was considered. This feasibility was established using a concept of diffusion bonding two layers of metallized films together forming a film-metal-film sandwich laminate. The permeability of kapton film to gaseous helium was reduced from a nominal ten = to the minus 9 power cc-mm/sq cm sec. cm Hg to ten to the minus 13 power cc-mm/ sq cm - sec. cm Hg with some values as low as ten to the minus 15 power cc - mm/sq cm m-sec - cm Hg being obtained. Similar reductions occurred in the liquid hydrogen permeability at -252 C. In the course of the program the permeability, flexibility and bond strength of plain, metalized and diffusion bond film were determined at +25 C, -195 C and -252 C. The cryogenic flexibility of Kapton film was reduced slightly due to the metallization process but no additional loss in flexibility resulted from the diffusion bonding process.
2010-11-30
approved climate zones) ► Dual flush toilets ► 1.5 GPM flow shower heads ► 0.5 GPM flow faucets ► Rainwater harvesting ► Permeable asphalt, permeable...for system with indirect evaporative pre-cooling Sustainability Measures ► Dual flush toilets ► 1.5 GPM flow shower heads, 0.5 GPM flow faucets...daylighting controls with 500 lux setpoint ► Dual flush toilets ►Waterless urinals ► 0.5 GPM flow faucets ► Rainwater harvesting ► Enhanced Commissioning
NASA Astrophysics Data System (ADS)
Aryal, Muna; Park, Juyoung; Vykhodtseva, Natalia; Zhang, Yong-Zhi; McDannold, Nathan
2015-03-01
Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the ‘blood tumor barrier’ (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood-brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg-1. This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823 ± 600, 1817 ± 732 and 2432 ± 448 ng g-1) in the control tumors at 9, 14 and 17 d. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P < 0.05, P < 0.01, and P < 0.0001 at days 9, 14, and 17, respectively) and were greater than the control tumors by a factor of two or more (2222 ± 784, 3687 ± 796 and 5658 ± 821 ng g-1) regardless of the stage of tumor growth. The transfer coefficient Ktrans was significantly (P < 0.05) enhanced compared to control tumors only at day 9 but not at day 14 or 17. These results suggest that FUS-induced enhancements in tumor drug delivery are relatively consistent over time, at least in this tumor model. These results are encouraging for the use of large drug carriers, as they suggest that even large/late-stage tumors can benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found to be variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da; hydrodynamic diameter: ≃2 nm). It may be necessary to use a larger MRI contrast agent to effectively evaluate the sonication-induced enhanced permeabilization in large/late-stage tumors when a large drug carrier such as a liposome is used.
Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C.; Konofagou, Elisa E.
2015-01-01
Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n = 60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 days thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: 1) the duration of the BBB opening (r2 = 0.77); 2) the permeability of the opened BBB (r2 = 0.82); 3) the likelihood of safe opening (P < 0.05, safe opening compared to cases of damage; P < 0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r2 = 0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions. PMID:26562661
Dash, Satyabrata; Swain, Sarat K
2013-09-12
Starch/silicon carbide (starch/SiC) bionanocomposites were synthesized by solution method using different wt% of silicon carbide with starch matrix. The interaction between starch and silicon carbide was studied by Fourier transform infrared (FTIR) spectroscopy. The structure of the bionanocomposites was investigated by X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM). Thermal property of starch/SiC bionanocomposites was measured and a significant enhancement of thermal resistance was noticed. The oxygen barrier property of the composites was studied and a substantial reduction in permeability was observed as compared to the virgin starch. The reduction of oxygen permeability with enhancement of thermal stability of prepared bionanocomposites may enable the materials suitable for thermal resistant packaging and adhesive applications. Copyright © 2013 Elsevier Ltd. All rights reserved.
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.
Coupled thermal–hydrological–mechanical modeling of CO 2 -enhanced coalbed methane recovery
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ma, Tianran; Rutqvist, Jonny; Oldenburg, Curtis M.
CO 2 -enhanced coalbed methane recovery, also known as CO 2 -ECBM, is a potential win-win approach for enhanced methane production while simultaneously sequestering injected anthropogenic CO 2 to decrease CO 2 emissions into the atmosphere. Here, CO 2 -ECBM is simulated using a coupled thermal–hydrological–mechanical (THM) numerical model that considers multiphase (gas and water) flow and solubility, multicomponent (CO 2 and CH 4 ) diffusion and adsorption, heat transfer and coal deformation. The coupled model is based on the TOUGH-FLAC simulator, which is applied here for the first time to model CO 2 -ECBM. The capacity of the simulatormore » for modeling methane production is verified by a code-to-code comparison with the general-purpose finite-element solver COMSOL. Then, the TOUGH-FLAC simulator is applied in an isothermal simulation to study the variations in permeability evolution during a CO 2 -ECBM operation while considering four different stress-dependent permeability models that have been implemented into the simulator. Finally, the TOUGH-FLAC simulator is applied in non-isothermal simulations to model THM responses during a CO 2 -ECBM operation.Our simulations show that the permeability evolution, mechanical stress, and deformation are all affected by changes in pressure, temperature and adsorption swelling, with adsorption swelling having the largest effect. The calculated stress changes do not induce any mechanical failure in the coal seam, except near the injection well in one case of a very unfavorable stress field.« less
Zhao, Shulan; Jia, Lina; Duo, Lian
2016-05-01
Phytoextraction has the potential to remove heavy metals from contaminated soil, and chelants can be used to improve the capabilities of phytoextraction. However, environmentally persistent chelants can cause metal leaching and groundwater pollution. A column experiment was conducted to evaluate the viability of biodegradable nitrilotriacetic acid (NTA) to increase the uptake of heavy metals (Cd, Cr, Ni, Pb, Cu, and Zn) by L. in municipal solid waste (MSW) compost and to evaluate the effect of two permeable barrier materials, bone meal and crab shell, on metal leaching. The application of NTA significantly increased the concentrations and uptake of heavy metals in . The enhancement was more pronounced at higher dosages of NTA. In the 15 mmol kg NTA treatment using a crab shell barrier, the Cr and Ni concentrations in the plant shoots increased by approximately 8- and 10-fold, respectively, relative to the control. However, the addition of NTA also caused significant heavy metal leaching from the MSW compost. Bone meal and crab shell barriers positioned between the compost and the subsoil were effective in preventing metal leaching down through the soil profile by the retention of metals in the barrier. The application of a biodegradable chelant and the use of permeable barriers is a viable form of enhanced phytoextraction to increase the removal of metals and to reduce possible leaching. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.
Panchatcharam, Manikandan; Salous, Abdel K; Brandon, Jason; Miriyala, Sumitra; Wheeler, Jessica; Patil, Pooja; Sunkara, Manjula; Morris, Andrew J; Escalante-Alcalde, Diana; Smyth, Susan S
2014-04-01
Lipid phosphate phosphatase 3 (LPP3), encoded by the PPAP2B gene, is an integral membrane enzyme that dephosphorylates, and thereby terminates, the G-protein-coupled receptor-mediated signaling actions of lysophosphatidic acid (LPA) and sphingosine-1-phosphate. LPP3 is essential for normal vascular development in mice, and a common PPAP2B polymorphism is associated with increased risk of coronary artery disease in humans. Herein, we investigate the function of endothelial LPP3 to understand its role in the development and human disease. We developed mouse models with selective LPP3 deficiency in endothelial and hematopoietic cells. Tyrosine kinase Tek promoter-mediated inactivation of Ppap2b resulted in embryonic lethality because of vascular defects. LPP3 deficiency in adult mice, achieved using a tamoxifen-inducible Cre transgene under the control of the Tyrosine kinase Tek promoter, enhanced local and systemic inflammatory responses. Endothelial, but not hematopoietic, cell LPP3 deficiency led to significant increases in vascular permeability at baseline and enhanced sensitivity to inflammation-induced vascular leak. Endothelial barrier function was restored by pharmacological or genetic inhibition of either LPA production by the circulating lysophospholipase D autotaxin or of G-protein-coupled receptor-dependent LPA signaling. Our results identify a role for the autotaxin/LPA-signaling nexus as a mediator of endothelial permeability in inflammation and demonstrate that LPP3 limits these effects. These findings have implications for therapeutic targets to maintain vascular barrier function in inflammatory states.
Coupled thermal–hydrological–mechanical modeling of CO 2 -enhanced coalbed methane recovery
Ma, Tianran; Rutqvist, Jonny; Oldenburg, Curtis M.; ...
2017-05-22
CO 2 -enhanced coalbed methane recovery, also known as CO 2 -ECBM, is a potential win-win approach for enhanced methane production while simultaneously sequestering injected anthropogenic CO 2 to decrease CO 2 emissions into the atmosphere. Here, CO 2 -ECBM is simulated using a coupled thermal–hydrological–mechanical (THM) numerical model that considers multiphase (gas and water) flow and solubility, multicomponent (CO 2 and CH 4 ) diffusion and adsorption, heat transfer and coal deformation. The coupled model is based on the TOUGH-FLAC simulator, which is applied here for the first time to model CO 2 -ECBM. The capacity of the simulatormore » for modeling methane production is verified by a code-to-code comparison with the general-purpose finite-element solver COMSOL. Then, the TOUGH-FLAC simulator is applied in an isothermal simulation to study the variations in permeability evolution during a CO 2 -ECBM operation while considering four different stress-dependent permeability models that have been implemented into the simulator. Finally, the TOUGH-FLAC simulator is applied in non-isothermal simulations to model THM responses during a CO 2 -ECBM operation.Our simulations show that the permeability evolution, mechanical stress, and deformation are all affected by changes in pressure, temperature and adsorption swelling, with adsorption swelling having the largest effect. The calculated stress changes do not induce any mechanical failure in the coal seam, except near the injection well in one case of a very unfavorable stress field.« less
Sun, Deqing; Xue, Aiying; Zhang, Bin; Lou, Haiyan; Shi, Huanying; Zhang, Xiumei
2015-12-01
Acetylpuerarin (AP) is an acetylated derivative of puerarin (PUE). The study aimed to prepare polysorbate 80-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles to improve the permeability of AP across the blood-brain barrier (BBB) and enhance its brain-protective effects. AP-loaded PLGA nanoparticles (AP-PLGA-NPs) were prepared using a solvent diffusion methodology. The NPs were characterized. The pharmacokinetics, tissue distributions and brain-protective effects of AP-PLGA-NPs were evaluated in animals. AP-PLGA-NPs were successfully prepared with a mean particle size of 145.0 nm and a zeta potential of -14.81 mV. The in-vitro release of AP from the PLGA-NPs showed a biphasic release profile. AP was metabolized into PUE in rats. The AUC0-∞ values of AP and PUE for AP-PLGA-NPs were 2.90- and 2.29-fold as great as those for AP solution, respectively. The values of the relative targeting efficiency in the brain were 2.40 and 2.58 for AP and PUE, and the ratios of peak concentration were 1.91 and 1.89 for AP and PUE, respectively. Compared with the crude drug, AP-PLGA-NPs showed better brain-protective effects in rats. Polysorbate 80-coated PLGA-NPs can improve the permeability of AP cross the BBB and enhance its brain-protective effects in rats. © 2015 Royal Pharmaceutical Society.
Pandaran Sudheeran, Subash; Jacob, Della; Natinga Mulakal, Johannah; Gopinathan Nair, Gopakumar; Maliakel, Abhilash; Maliakel, Balu; Kuttan, Ramadasan; Im, Krishnakumar
2016-06-01
Drug delivery systems capable of delivering free (unconjugated) curcuminoids is of great therapeutic significance, since the absorption of bioactive and permeable form plays a key factor in mediating the efficacy of a substance which undergoes rapid biotransformation. Considering the recent understanding on the relatively high bioactivities and blood-brain-barrier permeability of free curcuminoids over their conjugated metabolites, the present human study investigated the safety, antioxidant efficacy, and bioavailability of CurQfen (curcumagalactomannoside [CGM]), a food-grade formulation of natural curcumin with fenugreek dietary fiber that has shown to possess improved blood-brain-barrier permeability and tissue distribution in rats. In this randomized double-blinded and placebo-controlled trial, 60 subjects experiencing occupational stress-related anxiety and fatigue were randomized to receive CGM, standard curcumin, and placebo for 30 days (500 mg twice daily). The study demonstrated the safety, tolerance, and enhanced efficacy of CGM in comparison with unformulated standard curcumin. A significant improvement in the quality of life (P < 0.05) with considerable reduction in stress (P < 0.001), anxiety (P < 0.001), and fatigue (P < 0.001) was observed among CGM-treated subjects as compared with the standard curcumin group, when monitored by SF-36, Perceived Stress Scale with 14 items, and Beck Anxiety Inventory scores. Improvement in the quality of life was further correlated with the significant enhancement in endogenous antioxidant markers (P < 0.01) and reduction in lipid peroxidation (P < 0.001). Further comparison of the free curcuminoids bioavailability after a single-dose (500 mg once per day) and repeated-dose (500 mg twice daily for 30 days) oral administration revealed enhanced absorption and improved pharmacokinetics of CGM upon both single- (30.7-fold) and repeated-dose (39.1-fold) administrations.
Tiwari, Yash V; Lu, Jianfei; Shen, Qiang; Cerqueira, Bianca; Duong, Timothy Q
2017-08-01
Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (K w ) across the blood-brain barrier in humans. This study aimed to evaluate the blood-brain barrier disruption in transient (60 min) ischemic stroke using K w magnetic resonance imaging with cross-validation by dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology in the same rats. The major findings were: (i) at 90 min after stroke (30 min after reperfusion), group K w magnetic resonance imaging data showed no significant blood-brain barrier permeability changes, although a few animals showed slightly abnormal K w . Dynamic contrast-enhanced magnetic resonance imaging confirmed this finding in the same animals. (ii) At two days after stroke, K w magnetic resonance imaging revealed significant blood-brain barrier disruption. Regions with abnormal K w showed substantial overlap with regions of hyperintense T 2 (vasogenic edema) and hyperperfusion. Dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology confirmed these findings in the same animals. The K w values in the normal contralesional hemisphere and the ipsilesional ischemic core two days after stroke were: 363 ± 17 and 261 ± 18 min -1 , respectively (P < 0.05, n = 9). K w magnetic resonance imaging is sensitive to blood-brain barrier permeability changes in stroke, consistent with dynamic contrast-enhanced magnetic resonance imaging and Evans blue extravasation. K w magnetic resonance imaging offers advantages over existing techniques because contrast agent is not needed and repeated measurements can be made for longitudinal monitoring or averaging.
Brandhonneur, Nolwenn; Dollo, Gilles; Ratajczak-Enselme, Maja; Deniau, Anne Laure; Chevanne, François; Estèbe, Jean Pierre; Legrand, Alain; Le Corre, Pascal
2011-02-14
Following epidural administration, cerebrospinal fluid bioavailability of local anesthetics is low, one major limiting factor being diffusion across the arachnoid mater barrier. The aim of this study was to evaluate the influence of absorption enhancers on the meningeal permeability of epidurally administered ropivacaine. Five enhancers known for their ability to increase drug permeability via transcellular and/or paracellular pathways, i.e. palmitoyl carnitine, ethylenediaminetetraacetic acid, sodium caprate, dodecylphosphocholine and pentylglycerol, were tested ex vivo on fresh specimen of meninges removed from cervical to lumbar level of rabbit spine following laminectomy and placed in diffusion chambers. Among them, sodium caprate lead to the best permeability improvement for both marker and drug (440% and 112% for mannitol and ropivacaine, respectively) and was therefore selected for in vivo study in a sheep model using microdialysis technique to evaluate epidural and intrathecal ropivacaine concentrations following epidural administration. Resulting dialysate and plasma concentrations were used to calculate pharmacokinetic parameters. Following sodium caprate pre-treatment, ropivacaine intrathecal maximal concentration (Cmax) was 1.6 times higher (78 ± 16 μg ml(-1) vs 129 ± 26 μg ml(-1), p<0.05) but the influence of the absorption enhancer was only effective the first 30 min following ropivacaine injection, as seen with the significantly increase of intrathecal AUC(0-30 min) (1629 ± 437 μg min ml(-1) vs 2477 ± 559 μg min ml(-1), p<0.05) resulting in a bioavailable fraction 130% higher 30 min after ropivavaine administration. Co-administration of local anesthetics with sodium caprate seems to allow a transient and reversible improvement of transmeningeal passage into intrathecal space. Copyright © 2010 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Zhang, R.; Borgia, A.; Daley, T. M.; Oldenburg, C. M.; Jung, Y.; Lee, K. J.; Doughty, C.; Altundas, B.; Chugunov, N.; Ramakrishnan, T. S.
2017-12-01
Subsurface permeable faults and fracture networks play a critical role for enhanced geothermal systems (EGS) by providing conduits for fluid flow. Characterization of the permeable flow paths before and after stimulation is necessary to evaluate and optimize energy extraction. To provide insight into the feasibility of using CO2 as a contrast agent to enhance fault characterization by seismic methods, we model seismic monitoring of supercritical CO2 (scCO2) injected into a fault. During the CO2 injection, the original brine is replaced by scCO2, which leads to variations in geophysical properties of the formation. To explore the technical feasibility of the approach, we present modeling results for different time-lapse seismic methods including surface seismic, vertical seismic profiling (VSP), and a cross-well survey. We simulate the injection and production of CO2 into a normal fault in a system based on the Brady's geothermal field and model pressure and saturation variations in the fault zone using TOUGH2-ECO2N. The simulation results provide changing fluid properties during the injection, such as saturation and salinity changes, which allow us to estimate corresponding changes in seismic properties of the fault and the formation. We model the response of the system to active seismic monitoring in time-lapse mode using an anisotropic finite difference method with modifications for fracture compliance. Results to date show that even narrow fault and fracture zones filled with CO2 can be better detected using the VSP and cross-well survey geometry, while it would be difficult to image the CO2 plume by using surface seismic methods.
NASA Astrophysics Data System (ADS)
Thiel, Stephan
2017-09-01
Hydraulic fracking is a geoengineering application designed to enhance subsurface permeability to maximize fluid and gas flow. Fracking is commonly used in enhanced geothermal systems (EGS), tight shale gas, and coal seam gas (CSG) plays and in CO_2 storage scenarios. Common monitoring methods include microseismics and mapping small earthquakes with great resolution associated with fracture opening at reservoir depth. Recently, electromagnetic (EM) methods have been employed in the field to provide an alternative way of direct detection of fluids as they are pumped in the ground. Surface magnetotelluric (MT) measurements across EGS show subtle yet detectable changes during fracking derived from time-lapse MT deployments. Changes are directional and are predominantly aligned with current stress field, dictating preferential fracture orientation, supported by microseismic monitoring of frack-related earthquakes. Modeling studies prior to the injection are crucial for survey design and feasibility of monitoring fracks. In particular, knowledge of sediment thickness plays a fundamental role in resolving subtle changes. Numerical forward modeling studies clearly favor some form of downhole measurement to enhance sensitivity; however, these have yet to be conclusively demonstrated in the field. Nevertheless, real surface-based monitoring examples do not necessarily replicate the expected magnitude of change derived from forward modeling and are larger than expected in some cases from EGS and CSG systems. It appears the injected fluid volume alone cannot account for the surface change in resistivity, but connectedness of pore space is also significantly enhanced and nonlinear. Recent numerical studies emphasize the importance of percolation threshold of the fracture network on both electrical resistivity and permeability, which may play an important role in accounting for temporal changes in surface EM measurements during hydraulic fracking.
Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni
2007-02-19
To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.
Permeability modes in fluctuating lipid membranes with DNA-translocating pores.
Moleiro, L H; Mell, M; Bocanegra, R; López-Montero, I; Fouquet, P; Hellweg, Th; Carrascosa, J L; Monroy, F
2017-09-01
Membrane pores can significantly alter not only the permeation dynamics of biological membranes but also their elasticity. Large membrane pores able to transport macromolecular contents represent an interesting model to test theoretical predictions that assign active-like (non-equilibrium) behavior to the permeability contributions to the enhanced membrane fluctuations existing in permeable membranes [Maneville et al. Phys. Rev. Lett. 82, 4356 (1999)]. Such high-amplitude active contributions arise from the forced transport of solvent and solutes through the open pores, which becomes even dominant at large permeability. In this paper, we present a detailed experimental analysis of the active shape fluctuations that appear in highly permeable lipid vesicles with large macromolecular pores inserted in the lipid membrane, which are a consequence of transport permeability events occurred in an osmotic gradient. The experimental results are found in quantitative agreement with theory, showing a remarkable dependence with the density of membrane pores and giving account of mechanical compliances and permeability rates that are compatible with the large size of the membrane pore considered. The presence of individual permeation events has been detected in the fluctuation time-series, from which a stochastic distribution of the permeation events compatible with a shot-noise has been deduced. The non-equilibrium character of the membrane fluctuations in a permeation field, even if the membrane pores are mere passive transporters, is clearly demonstrated. Finally, a bio-nano-technology outlook of the proposed synthetic concept is given on the context of prospective uses as active membrane DNA-pores exploitable in gen-delivery applications based on lipid vesicles. Copyright © 2017 Elsevier B.V. All rights reserved.
Ca2+ permeability and Na+ conductance in cellular toxicity caused by hyperactive DEG/ENaC channels.
Matthewman, Cristina; Miller-Fleming, Tyne W; Miller, David M; Bianchi, Laura
2016-12-01
Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca 2+ overload. Mammalian ASIC1a channels and MEC-4(d) neurotoxic channels in Caenorhabditis elegans both conduct Na + and Ca 2+ , raising the possibility that direct Ca 2+ influx through these channels contributes to intracellular Ca 2+ overload. However, we showed that the homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca 2+ permeable, yet it is neurotoxic, suggesting that Na + influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca 2+ block in the Xenopus oocyte expression system. Thus, MEC-4(d) and UNC-8(d) differ both in current amplitude and Ca 2+ permeability. Given that these two channels show a striking difference in toxicity, we wondered how Na + conductance vs. Ca 2+ permeability contributes to cell death. To address this question, we built an UNC-8/MEC-4 chimeric channel that retains the calcium permeability of MEC-4 and characterized its properties in Xenopus oocytes. Our data support the hypothesis that for Ca 2+ -permeable DEG/ENaC channels, both Ca 2+ permeability and Na + conductance contribute to toxicity. However, for Ca 2+ -impermeable DEG/ENaCs (e.g., UNC-8), our evidence shows that constitutive Na + conductance is sufficient to induce toxicity, and that this effect is enhanced as current amplitude increases. Our work further refines the contribution of different channel properties to cellular toxicity induced by hyperactive DEG/ENaC channels. Copyright © 2016 the American Physiological Society.
Ca2+ permeability and Na+ conductance in cellular toxicity caused by hyperactive DEG/ENaC channels
Matthewman, Cristina; Miller-Fleming, Tyne W.; Miller, David M.
2016-01-01
Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca2+ overload. Mammalian ASIC1a channels and MEC-4(d) neurotoxic channels in Caenorhabditis elegans both conduct Na+ and Ca2+, raising the possibility that direct Ca2+ influx through these channels contributes to intracellular Ca2+ overload. However, we showed that the homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca2+ permeable, yet it is neurotoxic, suggesting that Na+ influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca2+ block in the Xenopus oocyte expression system. Thus, MEC-4(d) and UNC-8(d) differ both in current amplitude and Ca2+ permeability. Given that these two channels show a striking difference in toxicity, we wondered how Na+ conductance vs. Ca2+ permeability contributes to cell death. To address this question, we built an UNC-8/MEC-4 chimeric channel that retains the calcium permeability of MEC-4 and characterized its properties in Xenopus oocytes. Our data support the hypothesis that for Ca2+-permeable DEG/ENaC channels, both Ca2+ permeability and Na+ conductance contribute to toxicity. However, for Ca2+-impermeable DEG/ENaCs (e.g., UNC-8), our evidence shows that constitutive Na+ conductance is sufficient to induce toxicity, and that this effect is enhanced as current amplitude increases. Our work further refines the contribution of different channel properties to cellular toxicity induced by hyperactive DEG/ENaC channels. PMID:27760755
Dhanikula, Renu Singh; Argaw, Anteneh; Bouchard, Jean-Francois; Hildgen, Patrice
2008-01-01
Therapeutic benefit in glial tumors is often limited due to low permeability of delivery systems across the blood-brain barrier (BBB), drug resistance, and poor penetration into the tumor tissue. In an attempt to overcome these hurdles, polyether-copolyester (PEPE) dendrimers were evaluated as drug carriers for the treatment of gliomas. Dendrimers were conjugated to d-glucosamine as the ligand for enhancing BBB permeability and tumor targeting. The efficacy of methotrexate (MTX)-loaded dendrimers was established against U87 MG and U 343 MGa cells. Permeability of rhodamine-labeled dendrimers and MTX-loaded dendrimers across the in vitro BBB model and their distribution into avascular human glioma tumor spheroids was also studied. Glucosylated dendrimers were found to be endocytosed in significantly higher amounts than nonglucosylated dendrimers by both the cell lines. IC 50 of MTX after loading in dendrimers was lower than that of the free MTX, suggesting that loading MTX in PEPE dendrimers increased its potency. Similar higher activity of MTX-loaded glucosylated and nonglucosylated dendrimers was found in the reduction of tumor spheroid size. These MTX-loaded dendrimers were able to kill even MTX-resistant cells highlighting their ability to overcome MTX resistance. In addition, the amount of MTX-transported across BBB was three to five times more after loading in the dendrimers. Glucosylation further increased the cumulative permeation of dendrimers across BBB and hence increased the amount of MTX available across it. Glucosylated dendrimers distributed through out the avascular tumor spheroids within 6 h, while nonglucosylated dendrimers could do so in 12 h. The results show that glucosamine can be used as an effective ligand not only for targeting glial tumors but also for enhanced permeability across BBB. Thus, glucosylated PEPE dendrimers can serve as potential delivery system for the treatment of gliomas.
Enhancing nZVI mobility in porous media using humate
NASA Astrophysics Data System (ADS)
Schmid, Doris; Micic Batka, Vesna; Gondikas, Andreas; Velimirovic, Milica; von der Kammer, Frank; Hofmann, Thilo
2016-04-01
The limited transport of nanoscale zero-valent iron (nZVI) particles in porous media is a major drawback for its use in groundwater remediation. Among other factors, transport of nZVI particles might be negatively affected by mineralogical and physical heterogeneities of the aquifer matrix. Carbonate minerals and iron oxides, for instance, provide positively charged patches which would further increase particle attachment to the sand grains. This study does assess the potential of sodium humate, a salt of humic acids, to enhance the mobility of nZVI particles. Humate is a non-toxic, inexpensive material extracted from natural oxidized lignite and obtained in commercial grade, which makes it advantageous for field applications. Humate is expected to shield the positively charged patches of the sand grains and consequently enhance nZVI mobility in porous media. In this study the humate was injected into an aquifer prior to injection of the nZVI particles. The potential of humate for enhancing the mobility of nZVI particles was tested in an array of columns packed with heterogeneous natural porous media of different mineralogical composition and sediment texture. The results demonstrated that without pre-injection of humates only limited mobility of nZVI particles can be obtained in all tested porous media. After the pre-injection of low concentration of humate (10 mg/L) the mobility of nZVI particles (1 g/L) was enhanced in all tested porous media. The magnitude of this enhancement was depended on the properties of the porous media. The largest improvement of nZVI mobility was observed for homogeneous quartz. This material had also the highest porosity (~ 40%), good sorting, and therefore a higher permeability compared to the other porous media tested. It is assumed that the higher permeability of this porous medium allowed an optimal distribution of humate, resulting in an approximately 6-fold enhancement of nZVI mobility. In carbonate-rich porous medium with a lower permeability a 1.5-fold enhancement of the nZVI mobility was observed. Enhanced nZVI mobility (up to 1.2-folds) was also observed for the porous media containing high quartz content and lower porosity. This might be attributed to the iron oxides minerals present in this porous medium. The results of this study showed that the pre-injection of humate can enhance the mobility of nZVI in various natural porous media. Enhancement of nZVI mobility was more pronounced in porous media with the highest permeability and porous media with higher carbonate or iron oxide content. The humates shield the positively charged patches and therefore make the overall charge of the porous media more negatively charged. Consequently, the mobility of the negatively charged nZVI particles due to electrosteric and electrostatic repulsion was promoted. Future work will focus on understanding the mechanisms leading to the different attachment of humates onto the porous media. This research receives funding from the European Union's Seventh Framework Programme FP7/2007-2013 under grant agreement n°309517.
Multiphase groundwater flow near cooling plutons
Hayba, D.O.; Ingebritsen, S.E.
1997-01-01
We investigate groundwater flow near cooling plutons with a computer program that can model multiphase flow, temperatures up to 1200??C, thermal pressurization, and temperature-dependent rock properties. A series of experiments examines the effects of host-rock permeability, size and depth of pluton emplacement, single versus multiple intrusions, the influence of a caprock, and the impact of topographically driven groundwater flow. We also reproduce and evaluate some of the pioneering numerical experiments on flow around plutons. Host-rock permeability is the principal factor influencing fluid circulation and heat transfer in hydrothermal systems. The hottest and most steam-rich systems develop where permeability is of the order of 10-15 m2. Temperatures and life spans of systems decrease with increasing permeability. Conduction-dominated systems, in which permeabilities are ???10-16m2, persist longer but exhibit relatively modest increases in near-surface temperatures relative to ambient conditions. Pluton size, emplacement depth, and initial thermal conditions have less influence on hydrothermal circulation patterns but affect the extent of boiling and duration of hydrothermal systems. Topographically driven groundwater flow can significantly alter hydrothermal circulation; however, a low-permeability caprock effectively decouples the topographically and density-driven systems and stabilizes the mixing interface between them thereby defining a likely ore-forming environment.
The mechanism of plasma-assisted penetration of NO2- in model tissues
NASA Astrophysics Data System (ADS)
He, Tongtong; Liu, Dingxin; Liu, Zhijie; Liu, Zhichao; Li, Qiaosong; Rong, Mingzhe; Kong, Michael G.
2017-11-01
Cold atmospheric plasmas are reportedly capable of enhancing the percutaneous absorption of drugs, which is a development direction of plasma medicine. This motivated us to study how the enhancement effect was realized. In this letter, gelatin gel films were used as surrogates of human tissues, NaNO2 was used as a representative of small-molecule drugs, and cross-field and linear-field plasma jets were used for the purpose of enhancing the penetration of NaNO2 through the gelatin gel films. The permeability of gelatin gel films was quantified by measuring the NO2- concentration in water which was covered by those films. It was found that the gas flow and electric field of cold plasmas played a crucial role in the permeability enhancement of the model tissues, but the effect of gas flow was mainly confined in the surface layer, while the effect of the electric field was holistic. Those effects might be attributed to the localized squeezing of particles by gas flow and the weakening of the ion-dipole interaction by the AC electric field. The enhancement effect decreases with the increasing mass fraction of gelatin because the macromolecules of gelatin could significantly hinder the penetration of small molecules in the model tissues.
NASA Astrophysics Data System (ADS)
Chen, Wei; Wang, Jun; Zhang, Bin; Wu, Qilei; Su, Xiaogang
2017-12-01
The multiscale approach has been adapted to enhance the electromagnetic interference shielding properties of carbon fiber (CF) veil epoxy-based composites. The Fe3O4 nanoparticles (NPs) were homogeneously dispersed in the epoxy matrix after surface modification by using silane coupling agent. The CF veil/Fe3O4 NPs/epoxy multiscale composites were manufactured by impregnating the CF veils with Fe3O4 NPs/epoxy mixture to prepare prepreg followed by vacuum bagging process. The electromagnetic interference shielding properties combined with the complex permittivity and complex permeability of the composites were investigated in the X-band (8.2-12.4 GHz) range. The total shielding effectiveness (SET) increases with increasing Fe3O4 NPs loadings and the maximum SET is 51.5 dB at low thickness of 1 mm. The incorporation of Fe3O4 NPs into the composites enhances the complex permittivity and complex permeability thus enhancing the electromagnetic wave absorption capability. The increased SET dominated by absorption loss SEA is attributed to the enhanced magnetic loss and dielectric loss generated by Fe3O4 NPs and multilayer construction of the composites. The microwave conductivity increases and the skin depth decreases with increasing Fe3O4 NPs loadings.
Ghosh, Priyanka; Lee, DoMin; Kim, Kyung Bo; Stinchcomb, Audra L
2014-01-01
The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetime following microneedle treatment and develop a 7 day transdermal system for naltrexone. Four different codrugs of naltrexone and diclofenac were compared in terms of stability and solubility. Transdermal flux, permeability and skin concentration of both parent drugs and codrugs were quantified to form a structure permeability relationship. The results indicated that all codrugs bioconverted in the skin. The degree of conversion was dependent on the structure, phenol linked codrugs were less stable compared to the secondary alcohol linked structures. The flux of naltrexone across microneedle treated skin and the skin concentration of diclofenac were higher for the phenol linked codrugs. The polyethylene glycol link enhanced solubility of the codrugs, which translated into flux enhancement. The current studies indicated that formulation stability of codrugs and the flux of naltrexone can be enhanced via structure design optimization. The polyethylene glycol linked naltrexone diclofenac codrug is better suited for a 7 day drug delivery system both in terms of stability and drug delivery.
Hong, Tao; Lai, Sophia C.; Mahurin, Shannon Mark; ...
2017-12-27
Here, a series of cross–linked, freestanding oligo(ethylene oxide)– co–(polydimethylsiloxane–norbornene) membranes with varied composition is synthesized via in situ ring–opening metathesis polymerization. These membranes show remarkably high CO 2 permeabilities (3400 Barrer) and their separation performance approaches the Robeson upper bound. The excellent permeability of these copolymer membranes provides great potential for real–world applications where enormous volumes of gases must be separated. The gas transport properties of these films are found to be directly proportional to oligo(ethylene oxide) content incorporation, which stems from the increased solubility selectivity change within the copolymer matrix. This work provides a systematic study of how gasmore » separation performance in rubbery membranes can be enhanced by tuning the CO 2–philicity of their constituent monomeric subunits.« less
NASA Astrophysics Data System (ADS)
Guo, Cheng; Yang, Zhihong; Shen, Shile; Liang, Juan; Xu, Guoyue
2018-05-01
Planar anisotropy carbonyl iron (PACI) particles were prepared from commercial spherical carbonyl iron particles through a high performance ball-milling technique. The paraffin composites with orientation of shape anisotropy field for these PACI particles were obtained by applying an external magnetic field during the fabrication process. The frequency-dependent complex permeability values of these prepared paraffin composites have been investigated in the frequency range of 1-18 GHz. The results demonstrate that the orientation of shape anisotropy field for these PACI particles can effectively increase the complex permeability and decrease the complex permittivity values. Benefit from the enhancement in the complex permeability and reduction in the complex permittivity, the better impedance matching condition can be obtained and thus the good microwave absorption performance can be achieved for the samples with enough magnetic field orientation time.
GROUNDWATER AND SOIL REMEDIATION USING ELECTRICAL FIELD
Enhancements of contaminants removal and degradation in low permeability soils by electrical fields are achieved by the processes of electrical heating, electrokinetics, and electrochemical reactions. Electrical heating increases soil temperature resulting in the increase of cont...
ELECTROCHEMICAL DEGRADATION OF POLYCHLOROBIPHENYLS
Granular graphite is an ideal conductive material for electrochemical reduction technology applications in the field. Granular graphite was used to enhance the transfer of chlorinated aliphatic compounds in saturated, low permeability soils by electroosmosis. It was also used to ...
Quantitative analysis of nano-pore geomaterials and representative sampling for digital rock physics
NASA Astrophysics Data System (ADS)
Yoon, H.; Dewers, T. A.
2014-12-01
Geomaterials containing nano-pores (e.g., shales and carbonate rocks) have become increasingly important for emerging problems such as unconventional gas and oil resources, enhanced oil recovery, and geologic storage of CO2. Accurate prediction of coupled geophysical and chemical processes at the pore scale requires realistic representation of pore structure and topology. This is especially true for chalk materials, where pore networks are small and complex, and require characterization at sub-micron scale. In this work, we apply laser scanning confocal microscopy to characterize pore structures and microlithofacies at micron- and greater scales and dual focused ion beam-scanning electron microscopy (FIB-SEM) for 3D imaging of nanometer-to-micron scale microcracks and pore distributions. With imaging techniques advanced for nano-pore characterization, a problem of scale with FIB-SEM images is how to take nanometer scale information and apply it to the thin-section or larger scale. In this work, several texture characterization techniques including graph-based spectral segmentation, support vector machine, and principal component analysis are applied for segmentation clusters represented by 1-2 FIB-SEM samples per each cluster. Geometric and topological properties are analyzed and lattice-Boltzmann method (LBM) is used to obtain permeability at several different scales. Upscaling of permeability to the Darcy scale (e.g., the thin-section scale) with image dataset will be discussed with emphasis on understanding microfracture-matrix interaction, representative volume for FIB-SEM sampling, and multiphase flow and reactive transport. Funding from the DOE Basic Energy Sciences Geosciences Program is gratefully acknowledged. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.
A Simulation Tool for Dynamic Contrast Enhanced MRI
Mauconduit, Franck; Christen, Thomas; Barbier, Emmanuel Luc
2013-01-01
The quantification of bolus-tracking MRI techniques remains challenging. The acquisition usually relies on one contrast and the analysis on a simplified model of the various phenomena that arise within a voxel, leading to inaccurate perfusion estimates. To evaluate how simplifications in the interstitial model impact perfusion estimates, we propose a numerical tool to simulate the MR signal provided by a dynamic contrast enhanced (DCE) MRI experiment. Our model encompasses the intrinsic and relaxations, the magnetic field perturbations induced by susceptibility interfaces (vessels and cells), the diffusion of the water protons, the blood flow, the permeability of the vessel wall to the the contrast agent (CA) and the constrained diffusion of the CA within the voxel. The blood compartment is modeled as a uniform compartment. The different blocks of the simulation are validated and compared to classical models. The impact of the CA diffusivity on the permeability and blood volume estimates is evaluated. Simulations demonstrate that the CA diffusivity slightly impacts the permeability estimates ( for classical blood flow and CA diffusion). The effect of long echo times is investigated. Simulations show that DCE-MRI performed with an echo time may already lead to significant underestimation of the blood volume (up to 30% lower for brain tumor permeability values). The potential and the versatility of the proposed implementation are evaluated by running the simulation with realistic vascular geometry obtained from two photons microscopy and with impermeable cells in the extravascular environment. In conclusion, the proposed simulation tool describes DCE-MRI experiments and may be used to evaluate and optimize acquisition and processing strategies. PMID:23516414
Kikuchi, Takayuki; Suzuki, Masahiko; Kusai, Akira; Iseki, Ken; Sasaki, Hitoshi; Nakashima, Kenichiro
2005-08-11
This study was conducted to clarify the penetration properties of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl]methylimidazole-5-carboxylic acid monohydrate (CS-088), an ophthalmic agent, and the mechanism of the permeability-enhancing effect of EDTA and boric acid (EDTA/boric acid) on the corneal penetration of CS-088. In the absence of additives, corneal permeability decreased with increasing concentration of CS-088 as CS-088 monomers self-associate to form dimers. Presence of EDTA/boric acid caused no significant changes in the physicochemical properties of CS-088, the apparent partition coefficient or the mean particle size of CS-088. EDTA/boric acid induced only a slight change in the zeta potential of liposomes used as a model of the biological membrane. On the other hand, EDTA/boric acid significantly increased membrane fluidity of liposomes, whereas other buffering agents tested did not. This effect was synergistic and concentration-dependent for both EDTA and boric acid as was observed in in vitro corneal penetration of CS-088. In accordance with the result, the rate of CS-088 permeation into the liposomes significantly increased by the addition of EDTA/boric acid. Therefore, it was demonstrated that EDTA/boric acid promotes corneal penetration of CS-088 through the transcellular pathway by increasing membrane fluidity. Conversely, other buffering agents decreased corneal permeability of CS-088 by inducing further self-association of CS-088 aggregates.
das Neves, José; Araújo, Francisca; Andrade, Fernanda; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno
2013-07-01
Prevention strategies such as the development of microbicides are thought to be valuable in the fight against HIV/AIDS. Despite recent achievements, there is still a long road ahead in the field, particularly at the level of drug formulation. Drug nanocarriers based on polymers may be useful in enhancing local drug delivery while limiting systemic exposure. We prepared differently surface-engineered poly(ε-caprolactone) (PCL) nanoparticles (NPs) and tested their ability to modulate the permeability and retention of dapivirine in cell monolayers and pig vaginal and rectal mucosa. NPs coated with poly(ethylene oxide) (PEO) were shown able to reduce permeability across monolayers/tissues, while modification of nanosystems with cetyl trimethylammonium bromide (CTAB) enhanced transport. In the case of coating NPs with sodium lauryl sulfate (SLS), dapivirine permeability was unchanged. All NPs increased monolayer/tissue drug retention as compared to unformulated dapivirine. This fact was associated, at least partially, to the ability of NPs to be taken up by cells or penetrate mucosal tissue. Cell and tissue toxicity was also affected differently by NPs: PEO modification decreased the in vitro (but not ex vivo) toxicity of dapivirine, while higher toxicity was generally observed for NPs coated with SLS or CTAB. Overall, presented results support that PCL nanoparticles are capable of modulating drug permeability and retention in cell monolayers and mucosal tissues relevant for vaginal and rectal delivery of microbicides. In particular, PEO-modified dapivirine-loaded PCL NPs may be advantageous in increasing drug residence at epithelial cell lines/mucosal tissues, which may potentially increase the efficacy of microbicide drugs.
A Study of Permeability Changes Due to Cold Fluid Circulation in Fractured Geothermal Reservoirs.
Gholizadeh Doonechaly, Nima; Abdel Azim, Reda R; Rahman, Sheik S
2016-05-01
Reservoir behavior due to injection and circulation of cold fluid is studied with a shear displacement model based on the distributed dislocation technique, in a poro-thermoelastic environment. The approach is applied to a selected volume of Soultz geothermal reservoir at a depth range of 3600 to 3700 m. Permeability enhancement and geothermal potential of Soultz geothermal reservoir are assessed over a stimulation period of 3 months and a fluid circulation period of 14 years. This study-by shedding light onto another source of uncertainty-points toward a special role for the fracture surface asperities in predicting the shear dilation of fractures. It was also observed that thermal stress has a significant impact on changing the reservoir stress field. The effect of thermal stresses on reservoir behavior is more evident over longer circulation term as the rock matrix temperature is significantly lowered. Change in the fracture permeability due to the thermal stresses can also lead to the short circuiting between the injection and production wells which in turn decreases the produced fluid temperature significantly. The effect of thermal stress persists during the whole circulation period as it has significant impact on the continuous increase in the flow rate due to improved permeability over the circulation period. In the current study, taking into account the thermal stress resulted in a decrease of about 7 °C in predicted produced fluid temperature after 14 years of cold fluid circulation; a difference which notably influences the potential prediction of an enhanced geothermal system. © 2015, National Ground Water Association.
NASA Astrophysics Data System (ADS)
Vera, I.
The National Electric Company of Venezuela, C.A.D.A.F.E., is sponsoring the development of this experiment which represents Venezuela's first scientific experiment in space. The apparatus for the automatic casting of polymer thin films will be contained in NASA's payload No. G-559 of the Get Away Special program for a future orbital space flight in the U.S. Space Shuttle. Semi-permeable polymer membranes have important applications in a variety of fields, such as medecine, energy, and pharmaceuticals, and in general fluid separation processes such as reverse osmosis, ultra-filtration, and electro-dialysis. The casting of semi-permeable membranes in space will help to identify the roles of convection in determining the strucutre of these membranes.
An investigation of microstructural characteristics of contact-lens polymers
NASA Technical Reports Server (NTRS)
Singh, Jag J.; Eftekhari, Abe; Upchurch, Billy T.; Burns, Karen S.
1990-01-01
The free volume and gas permeability in several contact lens specimens were measured as part of a Space Commercialization Program. Free volume was measured using positron lifetime spectroscopy, while permeability for O2, N2, CO2 gases was measured using mass spectrometry and polarography. Permeability for all gases increases with the mean free volume cell size in the test samples. As might be expected, the specimens with the highest free volume fraction also exhibit the lowest Rockwell Hardness Number. An interesting corollary is the finding that the presence of fluorine atoms in the lens chemical structure inhibits filling up of their free volume cells. This is expected to allow the lenses to breathe freely while in actual use.
Critical Dynamics of Gravito-Convective Mixing in Geological Carbon Sequestration
Soltanian, Mohamad Reza; Amooie, Mohammad Amin; Dai, Zhenxue; Cole, David; Moortgat, Joachim
2016-01-01
When CO2 is injected in saline aquifers, dissolution causes a local increase in brine density that can cause Rayleigh-Taylor-type gravitational instabilities. Depending on the Rayleigh number, density-driven flow may mix dissolved CO2 throughout the aquifer at fast advective time-scales through convective mixing. Heterogeneity can impact density-driven flow to different degrees. Zones with low effective vertical permeability may suppress fingering and reduce vertical spreading, while potentially increasing transverse mixing. In more complex heterogeneity, arising from the spatial organization of sedimentary facies, finger propagation is reduced in low permeability facies, but may be enhanced through more permeable facies. The connectivity of facies is critical in determining the large-scale transport of CO2-rich brine. We perform high-resolution finite element simulations of advection-diffusion transport of CO2 with a focus on facies-based bimodal heterogeneity. Permeability fields are generated by a Markov Chain approach, which represent facies architecture by commonly observed characteristics such as volume fractions. CO2 dissolution and phase behavior are modeled with the cubic-plus-association equation-of-state. Our results show that the organization of high-permeability facies and their connectivity control the dynamics of gravitationally unstable flow. We discover new flow regimes in both homogeneous and heterogeneous media and present quantitative scaling relations for their temporal evolution. PMID:27808178
Optomagnetic composite medium with conducting nanoelements
NASA Astrophysics Data System (ADS)
Panina, L. V.; Grigorenko, A. N.; Makhnovskiy, D. P.
2002-10-01
A type of metal-dielectric composites has been proposed that is characterized by a resonancelike behavior of the effective permeability μeff in the infrared and visible spectral ranges. This material can be referred to as an optomagnetic medium. It consists of conducting inclusions in the shape of nonclosed contours or pairs of parallel sticks with length of 50-100 nm embedded in a dielectric matrix. The analytical formalism developed is based on solving the scattering problem for considered inclusions with impedance boundary condition, which yields the current and charge distributions within the inclusions. The magnetic properties originated by induced currents are enhanced by localized plasmon modes, which make an inclusion resonate at a much lower frequency than that of the half-wavelength requirement at microwaves. It implies that microstructure can be made on a scale much less than the wavelength and the effective permeability is a valid concept. The presence of the effective magnetic permeability and its resonant properties lead to unusual optical effects and open interesting applications. In particular, the condition for Brewster's angle becomes different resulting in reflectionless normal incidence from air (vacuum) if the effective permeability and permittivity are the same. The resonant behavior of the effective permeability of the proposed optomagnetic medium could be used for creation of optical polarizes, filters, phase shifters, and selective lenses.
Angelova, N; Hunkeler, D
2001-01-01
Capsules were obtained by interpolymer complexation between chitosan (polycation) and sodium hexametaphosphate (SMP, oligoanion). The effect of the preparation conditions on the capsule characteristics was evaluated. Specifically, the influence of variables such as pH, ionic strength, reagent concentration, and additives on the capsule permeability properties was investigated using dextran as a model permeant. The capsule membrane permeability was found to increase by decreasing the chitosan/SMP ratio as well as adding mannitol to the oligoanion recipient bath. Increasing the ionic strength or the pH of the initial chitosan solution was also found to enhance the membrane permeability, moving the membrane exclusion limit to higher values. Generally, the capsules prepared tinder all tested conditions had a relatively low permeability which rarely exceeded a molecular cut-off of 40 kD based on dextran standards. Furthermore, the diffusion rate showed a strong temporal dependence, indicating that the capsules prepared under various conditions exhibit different apparent pore size densities on the surface. The results indicated that, in order to obtain the desired capsule mass-transfer properties, the preparation conditions should be carefully considered and adjusted. Adding a polyol as well as low salt amount (less than 0.15%) is preferable as a means of modulating the diffusion characteristics, without disturbing the capsule mechanical stability.
Intestinal permeability of forskolin by in situ single pass perfusion in rats.
Liu, Zhen-Jun; Jiang, Dong-bo; Tian, Lu-Lu; Yin, Jia-Jun; Huang, Jian-Ming; Weng, Wei-Yu
2012-05-01
The intestinal permeability of forskolin was investigated using a single pass intestinal perfusion (SPIP) technique in rats. SPIP was performed in different intestinal segments (duodenum, jejunum, ileum, and colon) with three concentrations of forskolin (11.90, 29.75, and 59.90 µg/mL). The investigations of adsorption and stability were performed to ensure that the disappearance of forskolin from the perfusate was due to intestinal absorption. The results of the SPIP study indicated that forskolin could be absorbed in all segments of the intestine. The effective permeability (P (eff)) of forskolin was in the range of drugs with high intestinal permeability. The P (eff) was highest in the duodenum as compared to other intestinal segments. The decreases of P (eff) in the duodenum and ileum at the highest forskolin concentration suggested a saturable transport process. The addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across the rat jejunum. The absorbed fraction of dissolved forskolin after oral administration in humans was estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved forskolin can be absorbed readily in the intestine. The low aqueous solubility of forskolin might be a crucial factor for its poor oral bioavailability. © Georg Thieme Verlag KG Stuttgart · New York.
Guo, Gepu; Lu, Lu; Ji, Hongfei; Ma, Yong; Dong, Rui; Tu, Juan; Guo, Xiasheng; Qiu, Yuanyuan; Wu, Junru; Zhang, Dong
2015-04-01
A 3-D scaffold culture system has been used to promote in producing functional chondrocytes for repairing damaged cartilage. In the present study, the low intensity pulse ultrasound (LIPUS) (P(-)=0, 0.055, 0.085 and 0.11 MPa) was applied to improve the porosity and permeability of a 3-D alginate scaffold which was beneficial for the nutrition supply and metabolism during cell growth in 3-D alginate scaffold. The porosity and permeability of the scaffold was quantitatively analyzed based on scanning electron microscopy examination and fluorescence image observation. The results suggest that, for the scaffold exposed to LIPUS, its porosity and permeability could be significantly enhanced by the increasing LIPUS amplitude, which might be induced by the microstreaming shear stress generated by ultrasound-driven microbubble oscillations. Furthermore, the assessments of cell proliferation and collagen II expression confirmed that chondrocytes growth could be effectively promoted in 3-D alginate scaffolds treated by LIPUS, because of the improved scaffold porosity and permeability might benefit cell growth space and nutrition supply. It should also be noticed that appropriate LIPUS driving parameters should be adapted to achieve optimized chondrocytes culture effect in 3-D alginate scaffold. Copyright © 2014 Elsevier B.V. All rights reserved.
Kabilan, Senthil; Jung, Hun Bok; Kuprat, Andrew P; Beck, Anthon N; Varga, Tamas; Fernandez, Carlos A; Um, Wooyong
2016-06-21
X-ray microtomography (XMT) imaging combined with three-dimensional (3D) computational fluid dynamics (CFD) modeling technique was used to study the effect of geochemical and geomechanical processes on fracture permeability in composite Portland cement-basalt caprock core samples. The effect of fluid density and viscosity and two different pressure gradient conditions on fracture permeability was numerically studied by using fluids with varying density and viscosity and simulating two different pressure gradient conditions. After the application of geomechanical stress but before CO2-reaction, CFD revealed fluid flow increase, which resulted in increased fracture permeability. After CO2-reaction, XMT images displayed preferential precipitation of calcium carbonate within the fractures in the cement matrix and less precipitation in fractures located at the cement-basalt interface. CFD estimated changes in flow profile and differences in absolute values of flow velocity due to different pressure gradients. CFD was able to highlight the profound effect of fluid viscosity on velocity profile and fracture permeability. This study demonstrates the applicability of XMT imaging and CFD as powerful tools for characterizing the hydraulic properties of fractures in a number of applications like geologic carbon sequestration and storage, hydraulic fracturing for shale gas production, and enhanced geothermal systems.
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
NASA Astrophysics Data System (ADS)
Tichauer, Kenneth M.; Osswald, Christian R.; Dosmar, Emily; Guthrie, Micah J.; Hones, Logan; Sinha, Lagnojita; Xu, Xiaochun; Mieler, William F.; St. Lawrence, Keith; Kang-Mieler, Jennifer J.
2015-06-01
Clinical symptoms of diabetic retinopathy are not detectable until damage to the retina reaches an irreversible stage, at least by today's treatment standards. As a result, there is a push to develop new, "sub-clinical" methods of predicting the onset of diabetic retinopathy before the onset of irreversible damage. With diabetic retinopathy being associated with the accumulation of long-term mild damage to the retinal vasculature, retinal blood vessel permeability has been proposed as a key parameter for detecting preclinical stages of retinopathy. In this study, a kinetic modeling approach used to quantify vascular permeability in dynamic contrast-enhanced medical imaging was evaluated in noise simulations and then applied to retinal videoangiography data in a diabetic rat for the first time to determine the potential for this approach to be employed clinically as an early indicator of diabetic retinopathy. Experimental levels of noise were found to introduce errors of less than 15% in estimates of blood flow and extraction fraction (a marker of vascular permeability), and fitting of rat retinal fluorescein angiography data provided stable maps of both parameters.
Quintanar-Guerrero, D; Ganem-Quintanar, A; Tapia-Olguín, P; Kalia, Y N; Buri, P
1998-07-01
The permeability of three imidazole antimycotics (miconazole nitrate, ketoconazole, and itraconazole) through the free edge of healthy human nail was evaluated in vitro using side-by-side diffusion cells. The influence of keratolytic substances (papain, urea, and salicylic acid) on the permeability of the antimycotics was also studied. The results suggested that the nail constituted an impermeable barrier for these antimycotics; it could be considered that the nail behaved as a hydrophilic gel membrane, through which drugs of low solubility could not permeate. The use of ethanol did not promote the passage of any of the antimycotic drugs. Although scanning electron microscopy indicated that the keratolytic substances had a significant effect on the nail surface (papain > salicylic acid > urea), the passage of the three antimycotics was not improved by pretreatment with salicylic acid alone (20% for 10 days), or by the application of the drug in a 40% urea solution. It was found that only the combined effects of papain (15% for 1 day) and salicylic acid (20% for 10 days) were capable of enhancing the permeability of the antimycotic.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Maserati, Lorenzo; Meckler, Stephen M.; Bachman, Jonathan E.
Despite the availability of chemistries to tailor the pore architectures of microporous polymer membranes for chemical separations, trade-offs in permeability and selectivity with functional group manipulations nevertheless persist, which ultimately places an upper bound on membrane performance. We introduce a new design strategy to uncouple these attributes of the membrane. Key to our success is the incorporation of phase-change metal-organic frameworks (MOFs) into the polymer matrix, which can be used to increase the solubility of a specific gas in the membrane, and thereby its permeability. We further show that it is necessary to scale the size of the phase-change MOFmore » to nanoscopic dimensions, in order to take advantage of this effect in a gas separation. Our observation of an increase in solubility and permeability of only one of the gases during steady-state permeability measurements suggests fast exchange between free and chemisorbed gas molecules within the MOF pores. While the kinetics of this exchange in phase-change MOFs are not yet fully understood, their role in enhancing the efficacy and efficiency of the separation is clearly a compelling new direction for membrane technology.« less
Lattice Boltzmann Simulation of Shale Gas Transport in Organic Nano-Pores
Zhang, Xiaoling; Xiao, Lizhi; Shan, Xiaowen; Guo, Long
2014-01-01
Permeability is a key parameter for investigating the flow ability of sedimentary rocks. The conventional model for calculating permeability is derived from Darcy's law, which is valid only for continuum flow in porous rocks. We discussed the feasibility of simulating methane transport characteristics in the organic nano-pores of shale through the Lattice Boltzmann method (LBM). As a first attempt, the effects of high Knudsen number and the associated slip flow are considered, whereas the effect of adsorption in the capillary tube is left for future work. Simulation results show that at small Knudsen number, LBM results agree well with Poiseuille's law, and flow rate (flow capacity) is proportional to the square of the pore scale. At higher Knudsen numbers, the relaxation time needs to be corrected. In addition, velocity increases as the slip effect causes non negligible velocities on the pore wall, thereby enhancing the flow rate inside the pore, i.e., the permeability. Therefore, the LBM simulation of gas flow characteristics in organic nano-pores provides an effective way of evaluating the permeability of gas-bearing shale. PMID:24784022
Recovery of ammonia and phosphate minerals from swine wastewater using gas-permeable membranes.
Vanotti, M B; Dube, P J; Szogi, A A; García-González, M C
2017-04-01
Gas-permeable membrane technology is useful to recover ammonia (NH 3 ) from liquid manures. In this study, phosphorus (P) recovery via MgCl 2 precipitation was enhanced by combining it with NH 3 recovery through gas-permeable membranes. Anaerobically digested swine wastewater containing approximately 2300 mg NH 4 + -N L -1 and 450 mg P L -1 was treated using submerged membranes plus low-rate aeration to recover the NH 3 from within the liquid and MgCl 2 to precipitate the P. The experiments included a first configuration where N and P were recovered sequentially and a second configuration with simultaneous recovery. The low-rate aeration reduced the natural carbonate, increased pH and accelerated NH 3 uptake by the gas-permeable membrane system, which in turn benefited P recovery. Phosphorus removal efficiency was >90% and P recovery efficiency was about 100%. With higher NH 3 capture, the recovered P contained higher P 2 O 5 content (37-46%, >98% available), similar to the composition of the biomineral newberyite (MgHPO 4 ·3H 2 O). Published by Elsevier Ltd.
New boundary conditions for oil reservoirs with fracture
NASA Astrophysics Data System (ADS)
Andriyanova, Elena; Astafev, Vladimir
2017-06-01
Based on the fact that most of oil fields are on the late stage of field development, it becomes necessary to produce hard-to-extract oil, which can be obtained only by use of enhance oil recovery methods. For example many low permeable or shale formations can be developed only with application of massive hydraulic fracturing technique. In addition, modern geophysical researches show that mostly oil bearing formations are complicated with tectonic faults of different shape and permeability. These discontinuities exert essential influence on the field development process and on the well performance. For the modeling of fluid flow in the reservoir with some area of different permeability, we should determine the boundary conditions. In this article for the first time the boundary conditions for the problem of fluid filtration in the reservoir with some discontinuity are considered. This discontinuity represents thin but long area, which can be hydraulic fracturing of tectonic fault. The obtained boundary condition equations allow us to take into account pressure difference above and below the section and different values of permeability.
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.
NASA Astrophysics Data System (ADS)
Zhang, Shifeng; Sheng, James J.
2017-11-01
Low-salinity water imbibition was considered an enhanced recovery method in shale oil/gas reservoirs due to the resulting hydration-induced fractures, as observed at ambient conditions. To study the effect of confining pressure and salinity on hydration-induced fractures, time-elapsed computerized tomography (CT) was used to obtain cross-sectional images of shale cores. Based on the CT data of these cross-sectional images, cut faces parallel to the core axial in the middle of the core and 3D fracture images were also reconstructed. To study the effects of confining pressure and salinity on shale pore fluid flowing, shale permeability was measured with Nitrogen (N2), distilled water, 4% KCl solution, and 8% KCl solution. With confining pressures increased to 2 MPa or more, either in distilled water or in KCl solutions of different salinities, fractures were observed to close instead to propagate at the end of the tests. The intrinsic permeabilities of #1 and #2 Mancos shale cores were 60.0 and 7000 nD, respectively. When tested with distilled water, the permeability of #1 shale sample with 20.0 MPa confining pressure loaded, and #2 shale sample with 2.5 MPa confining pressure loaded, decreased to 0.45 and 15 nD, respectively. Using KCl can partly mitigate shale permeability degradation. Compared to 4% KCl, 8% KCl can decrease more permeability damage. From this point of view, high salinity KCl solution should be required for the water-based fracturing fluid.
Assessment of Jahn permeable mortar system in a historic bridge abutment application.
DOT National Transportation Integrated Search
2015-06-01
Increasingly, the importance of historic preservation is competing with the requirements to enhance : structural capacity of older unique structures. Preservation of the functional and aesthetic qualities limits : potential change to meet the expande...
Clearance Pathways and Tumor Targeting of Imaging Nanoparticles
Yu, Mengxiao; Zheng, Jie
2016-01-01
A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies. PMID:26149184
Cryptic antifungal compounds active by synergism with polyene antibiotics.
Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya
2016-04-01
The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
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.
Bachman, Jonathan E; Smith, Zachary P; Li, Tao; Xu, Ting; Long, Jeffrey R
2016-08-01
The implementation of membrane-based separations in the petrochemical industry has the potential to reduce energy consumption significantly relative to conventional separation processes. Achieving this goal, however, requires the development of new membrane materials with greater selectivity, permeability and stability than available at present. Here, we report composite materials consisting of nanocrystals of metal-organic frameworks dispersed within a high-performance polyimide, which can exhibit enhanced selectivity for ethylene over ethane, greater ethylene permeability and improved membrane stability. Our results suggest that framework-polymer interactions reduce chain mobility of the polymer while simultaneously boosting membrane separation performance. The increased stability, or plasticization resistance, is expected to improve membrane utility under real process conditions for petrochemical separations and natural gas purification. Furthermore, this approach can be broadly applied to numerous polymers that encounter aggressive environments, potentially making gas separations possible that were previously inaccessible to membranes.
Self-Organizing Fluid Convection Patterns in an en Echelon Fault Array
NASA Astrophysics Data System (ADS)
Patterson, James W.; Driesner, Thomas; Matthai, Stephan K.
2018-05-01
We present three-dimensional numerical simulations of natural convection in buried, vertical en echelon faults in impermeable host rock. Despite the fractures being hydraulically disconnected, convection within each fracture alters the temperature field in the surrounding host rock, altering convection in neighboring fractures. This leads to self-organization of coherent patterns of upward/downward flow and heating/cooling of the host rock spanning the entire fault array. This "synchronization" effect occurs when fracture spacing is less than the width of convection cells within the fractures, which is controlled by fracture transmissivity (permeability times thickness) and heterogeneity. Narrow fracture spacing and synchronization enhance convective fluid flow within fractures and cause convection to initiate earlier, even lowering the critical transmissivity necessary for convection initiation. Heat flow through the en echelon region, however, is enhanced only in low-transmissivity fractures, while heat flow in high-permeability fractures is reduced due to thermal interference between fractures.
Bulger, Carrie A; Matthews, Russell A; Hoffman, Mark E
2007-10-01
While researchers are increasingly interested in understanding the boundaries surrounding the work and personal life domains, few have tested the propositions set forth by theory. Boundary theory proposes that individuals manage the boundaries between work and personal life through processes of segmenting and/or integrating the domains. The authors investigated boundary management profiles of 332 workers in an investigation of the segmentation-integration continuum. Cluster analysis indicated consistent clusters of boundary management practices related to varying segmentation and integration of the work and personal life domains. But, the authors suggest that the segmentation-integration continuum may be more complicated. Results also indicated relationships between boundary management practices and work-personal life interference and work-personal life enhancement. Less flexible and more permeable boundaries were related to more interference, while more flexible and more permeable boundaries were related to more enhancement.
Visual detection of gas shows from coal core and cuttings using liquid leak detector
Barker, C.E.
2006-01-01
Portions of core or cutting samples that have active gas shows can be identified by applying a liquid leak detector to the core surface. Although these gas shows can be caused by manmade changes to the coals' internal structure and surface of the core during the coring process, in many cases, the marked gas shows overlie changes in maceral composition, subtle fractures or coal, coal structure and so forth that seemingly are places where natural primary permeability is higher and gas shows would be favored. Given the limited time available for core description before a core is closed in a canister, using the liquid leak detector method to mark gas shows enhances core description by providing a photographic record of places of apparently increased gas flow likely related to enhanced coal permeability that cannot be easily detected otherwise.
Karageorgis, Anastassia; Dufort, Sandrine; Sancey, Lucie; Henry, Maxime; Hirsjärvi, Samuli; Passirani, Catherine; Benoit, Jean-Pierre; Gravier, Julien; Texier, Isabelle; Montigon, Olivier; Benmerad, Mériem; Siroux, Valérie; Barbier, Emmanuel L.; Coll, Jean-Luc
2016-01-01
Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines. PMID:26892874
Karageorgis, Anastassia; Dufort, Sandrine; Sancey, Lucie; Henry, Maxime; Hirsjärvi, Samuli; Passirani, Catherine; Benoit, Jean-Pierre; Gravier, Julien; Texier, Isabelle; Montigon, Olivier; Benmerad, Mériem; Siroux, Valérie; Barbier, Emmanuel L; Coll, Jean-Luc
2016-02-19
Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Warpinski, N.R.; Branagan, P.T.
Altered-stress fracturing is a concept whereby a hydraulic fracture in one well is reoriented by another hydraulic fracture in a nearby location. The application is in tight, naturally fractured, anisotropic reservoirs in which conventional hydraulic fractures parallel the highly permeable natural fractures and little production enhancement is achieved by conventional hydraulic fracturing. Altered-stress fracturing can modify the stress field so that hydraulic fractures propagate across the permeable natural fractures. A field test was conducted in which stress changes of 250 to 300 psi (1.7 to 2.1 MPa) were measured in an offset well 120 ft (37 m) away during relativelymore » small minifracs in a production well. These results show that stress-altered fracturing is possible at this site and others. Analytic and finite element calculations quantify the effects of layers, stresses, and crack size. Reservoir calculations show significant enhancement compared to conventional treatments. 21 refs., 12 figs., 3 tabs.« less
Sonoporation at Small and Large Length Scales: Effect of Cavitation Bubble Collapse on Membranes.
Fu, Haohao; Comer, Jeffrey; Cai, Wensheng; Chipot, Christophe
2015-02-05
Ultrasound has emerged as a promising means to effect controlled delivery of therapeutic agents through cell membranes. One possible mechanism that explains the enhanced permeability of lipid bilayers is the fast contraction of cavitation bubbles produced on the membrane surface, thereby generating large impulses, which, in turn, enhance the permeability of the bilayer to small molecules. In the present contribution, we investigate the collapse of bubbles of different diameters, using atomistic and coarse-grained molecular dynamics simulations to calculate the force exerted on the membrane. The total impulse can be computed rigorously in numerical simulations, revealing a superlinear dependence of the impulse on the radius of the bubble. The collapse affects the structure of a nearby immobilized membrane, and leads to partial membrane invagination and increased water permeation. The results of the present study are envisioned to help optimize the use of ultrasound, notably for the delivery of drugs.
Saoji, Suprit D; Dave, Vivek S; Dhore, Pradip W; Bobde, Yamini S; Mack, Connor; Gupta, Deepak; Raut, Nishikant A
2017-10-15
In an attempt to improve the solubility and permeability of Standardized Bacopa Extract (SBE), a complexation approach based on phospholipid was employed. A solvent evaporation method was used to prepare the SBE-phospholipid complex (Bacopa Naturosome, BN). The formulation and process variables were optimized using a central-composite design. The formation of BN was confirmed by photomicroscopy, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). The saturation solubility, the in-vitro dissolution, and the ex-vivo permeability studies were used for the functional evaluation of the prepared complex. BN exhibited a significantly higher aqueous solubility compared to the pure SBE (20-fold), or the physical mixture of SBE and the phospholipid (13-fold). Similarly, the in-vitro dissolution revealed a significantly higher efficiency of the prepared complex (BN) in releasing the SBE (>97%) in comparison to the pure SCE (~42%), or the physical mixture (~47%). The ex-vivo permeation studies showed that the prepared BN significantly improved the permeation of SBE (>90%), compared to the pure SBE (~21%), or the physical mixture (~24%). Drug-phospholipid complexation may thus be a promising strategy for solubility enhancement of bioactive phytoconstituents. Copyright © 2016 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, Minjee; Lee, Byeongdu; Leal, Cecilia
Here, we present new structures of soft-material thin films that augment the functionality of substrate-mediated delivery systems. A hybrid material composed of phospholipids and block copolymers adopts a multilayered membrane structure supported on a solid surface. The hybrid films comprise intentional intramembrane heterogeneities that register across multilayers. These stacked domains convey unprecedented enhancement and control of permeability of solutes across micrometer-thick films. Using grazing incidence X-ray scattering, phase contrast atomic force microscopy, and confocal microscopy, we observed that in each lamella, lipid and polymers partition unevenly within the membrane plane segregating into lipid- or polymer-rich domains. Interestingly, we found evidencemore » that like-domains align in registry across multilayers, thereby making phase separation three-dimensional. Phase boundaries exist over extended length scales to compensate the height mismatch between lipid and polymer molecules. We show that microphase separation in hybrid films can be exploited to augment the capability of drug-eluting substrates. Lipid–polymer hybrid films loaded with paclitaxel show synergistic permeability of drug compared to single-component counterparts. We present a thorough structural study of stacked lipid–polymer hybrid membranes and propose that the presence of registered domains and domain boundaries impart enhanced drug release functionality. This work offers new perspectives in designing thin films for controlled delivery applications« less
Kang, Minjee; Lee, Byeongdu; Leal, Cecilia
2017-10-20
Here, we present new structures of soft-material thin films that augment the functionality of substrate-mediated delivery systems. A hybrid material composed of phospholipids and block copolymers adopts a multilayered membrane structure supported on a solid surface. The hybrid films comprise intentional intramembrane heterogeneities that register across multilayers. These stacked domains convey unprecedented enhancement and control of permeability of solutes across micrometer-thick films. Using grazing incidence X-ray scattering, phase contrast atomic force microscopy, and confocal microscopy, we observed that in each lamella, lipid and polymers partition unevenly within the membrane plane segregating into lipid- or polymer-rich domains. Interestingly, we found evidencemore » that like-domains align in registry across multilayers, thereby making phase separation three-dimensional. Phase boundaries exist over extended length scales to compensate the height mismatch between lipid and polymer molecules. We show that microphase separation in hybrid films can be exploited to augment the capability of drug-eluting substrates. Lipid–polymer hybrid films loaded with paclitaxel show synergistic permeability of drug compared to single-component counterparts. We present a thorough structural study of stacked lipid–polymer hybrid membranes and propose that the presence of registered domains and domain boundaries impart enhanced drug release functionality. This work offers new perspectives in designing thin films for controlled delivery applications« less
Ma, Tianran; Rutqvist, Jonny; Oldenburg, Curtis M.; ...
2017-06-03
This study presents the development and application of a fully coupled two-phase (methane and water) flow, transport, and poromechanics num erical model for the analysis of geomechanical impacts on coalbed methane (CBM) production. The model considers changes in two-phase fluid flow properties, i.e., coal porosity, permeability, water retention, and relative permeability curves through changes in cleat fractures induced by effective stress variations and desorption-induced shrinkage. The coupled simulator is first verified for poromechanics coupling, and simulation parameters of a CBM reservoir model are calibrated by history matching against one year of CBM production field data from Shanxi Province, China. Then,more » the verified simulator and the calibrated CBM reservoir model are used for predicting the impact of geomechanics on the production rate for twenty years of continuous CBM production. The simulation results show that desorption-induced shrinkage is the dominant process in increasing permeability in the near wellbore region. Away from the wellbore, desorption-induced shrinkage is weaker, and permeability is reduced by pressure depletion and increased effective stress. A sensitivity analysis shows that for coal with a higher sorption strain, a larger initial Young's modulus and a smaller Poisson's ratio promote the enhancement of permeability as well as an increased production rate. Moreover, the conceptual model of the cleat system, whether dominated by vertical cleats with permeability correlated to horizontal stress or with permeability correlated to mean stress, can have a significant impact on the predicted production rate. Overall, the study clearly demonstrates and confirms the critical importance of considering geomechanics for an accurate prediction of CBM production.« less
NASA Astrophysics Data System (ADS)
Illangasekare, T. H.; Agartan Karacaer, E.; Vargas-Johnson, J.; Cihan, A.; Birkholzer, J. T.
2017-12-01
It is expected that heterogeneity of the deep geologic formation to play a key role in both trapping of supercritical CO2 and its mixing in the formation brine. In previously reported research by the authors, a set of laboratory experiments and field-scale simulations were used to show that convective mixing and diffusion controlled trapping are two important mechanisms that contribute to the dissolution trapping in multilayered systems with homogeneous low-permeability zones such as shale. However, these low-permeability layers (e.g. shale) are not always homogeneous due to their composition and texture variations in addition to the presence of faults, fractures and fissures. In this study, we investigated the potential outcomes of heterogeneity present within these semi-confining low-permeability layers in regards to mixing and storage of dissolved CO2. An intermediate-scale laboratory experiment was designed to investigate the contribution of convective mixing, diffusion controlled trapping and back diffusion to long-term storage of dissolved CO2 in multilayered formations with heterogeneous low-permeability layers. The experiment was performed using a surrogate fluid combination to represent dissolved CO2 and brine under ambient pressure and temperature conditions. After verifying the numerical model with the experimental results, different distributions of the same low-permeability materials having similar volume ratios with the experimentally studied scenario were tested numerically. The experiment and modeling results showed that connectivity of higher permeability material within the semi-confining low-permeability layers contributes to mixing through brine leakage between upper and lower aquifers, storage through diffusion, and in the long term, back diffusion of stored mass due to reversed concentration gradient.
Convective mixing in vertically-layered porous media: The linear regime and the onset of convection
NASA Astrophysics Data System (ADS)
Ghorbani, Zohreh; Riaz, Amir; Daniel, Don
2017-08-01
We study the effect of permeability heterogeneity on the stability of gravitationally unstable, transient, diffusive boundary layers in porous media. Permeability is taken to vary periodically in the horizontal plane normal to the direction of gravity. In contrast to the situation for vertical permeability variation, the horizontal perturbation structures are multimodal. We therefore use a two-dimensional quasi-steady eigenvalue analysis as well as a complementary initial value problem to investigate the stability behavior in the linear regime, until the onset of convection. We find that thick permeability layers enhance instability compared with thin layers when heterogeneity is increased. On the contrary, for thin layers the instability is weakened progressively with increasing heterogeneity to the extent that the corresponding homogeneous case is more unstable. For high levels of heterogeneity, we find that a small change in the permeability field results in large variations in the onset time of convection, similar to the instability event in the linear regime. However, this trend does not persist unconditionally because of the reorientation of vorticity pairs due to the interaction of evolving perturbation structures with heterogeneity. Consequently, an earlier onset of instability does not necessarily imply an earlier onset of convection. A resonant amplification of instability is observed within the linear regime when the dominant perturbation mode is equal to half the wavenumber of permeability variation. On the other hand, a substantial damping occurs when the perturbation mode is equal to the harmonic and sub-harmonic components of the permeability wavenumber. The phenomenon of such harmonic interactions influences both the onset of instability as well as the onset of convection.
Dotson, Rachel J; Smith, Casey R; Bueche, Kristina; Angles, Gary; Pias, Sally C
2017-06-06
Cholesterol is widely known to alter the physical properties and permeability of membranes. Several prior works have implicated cell membrane cholesterol as a barrier to tissue oxygenation, yet a good deal remains to be explained with regard to the mechanism and magnitude of the effect. We use molecular dynamics simulations to provide atomic-resolution insight into the influence of cholesterol on oxygen diffusion across and within the membrane. Our simulations show strong overall agreement with published experimental data, reproducing the shapes of experimental oximetry curves with high accuracy. We calculate the upper-limit transmembrane oxygen permeability of a 1-palmitoyl,2-oleoylphosphatidylcholine phospholipid bilayer to be 52 ± 2 cm/s, close to the permeability of a water layer of the same thickness. With addition of cholesterol, the permeability decreases somewhat, reaching 40 ± 2 cm/s at the near-saturating level of 62.5 mol % cholesterol and 10 ± 2 cm/s in a 100% cholesterol mimic of the experimentally observed noncrystalline cholesterol bilayer domain. These reductions in permeability can only be biologically consequential in contexts where the diffusional path of oxygen is not water dominated. In our simulations, cholesterol reduces the overall solubility of oxygen within the membrane but enhances the oxygen transport parameter (solubility-diffusion product) near the membrane center. Given relatively low barriers to passing from membrane to membrane, our findings support hydrophobic channeling within membranes as a means of cellular and tissue-level oxygen transport. In such a membrane-dominated diffusional scheme, the influence of cholesterol on oxygen permeability is large enough to warrant further attention. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Permeability Evolution of Propped Artificial Fractures in Green River Shale
NASA Astrophysics Data System (ADS)
Li, Xiang; Feng, Zijun; Han, Gang; Elsworth, Derek; Marone, Chris; Saffer, Demian; Cheon, Dae-Sung
2017-06-01
This paper compares the evolution of permeability with effective stress in propped fractures in shale for native CH4 compared with that for sorbing CO2, slightly sorbing N2 and non-sorbing He. We examine the response for laboratory experiments on artificial propped fractures in Green River Shale to explore mechanisms of proppant embedment and fracture diagenesis. Split cylindrical specimens sandwich a proppant bead-pack at a constant confining stress of 20 MPa and with varied pore pressure. Permeability and sorption characteristics are measured with the pulse transient method. To explore the effect of swelling and embedment on fracture surface geometry, we measure the evolution of conductivity characteristics for different proppant geometries (single layer vs. multilayer), gas saturation and specimen variation in order to simulate both production and enhanced gas recovery. The resulting morphology of embedment is measured by white light interferometry and characterized via surface roughness parameter of mean, maximum and root-mean-square amplitudes. For both strongly (CO2, CH4) and slightly adsorptive gases (N2), the permeability first decreases with an increase in gas pressure due to swelling before effective stress effects dominate above the Langmuir pressure threshold. CO2 with its highest adsorption affinity produces the lowest permeability among these three gas permeants. Monolayer propped specimens show maximum swelling and lowered k/k 0 ratio and increased embedment recorded in the surface roughness relative to the multilayered specimens. Permeabilities measured for both injection and depletion cycles generally overlap and are repeatable with little hysteresis. This suggests the dominant role of reversible swelling over irreversible embedment. Gas permeant composition and related swelling have an important effect on the permeability evolution of shales.
Convective mixing in vertically-layered porous media: The linear regime and the onset of convection
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ghorbani, Zohreh; Riaz, Amir; Daniel, Don
In this paper, we study the effect of permeability heterogeneity on the stability of gravitationally unstable, transient, diffusive boundary layers in porous media. Permeability is taken to vary periodically in the horizontal plane normal to the direction of gravity. In contrast to the situation for vertical permeability variation, the horizontal perturbation structures are multimodal. We therefore use a two-dimensional quasi-steady eigenvalue analysis as well as a complementary initial value problem to investigate the stability behavior in the linear regime, until the onset of convection. We find that thick permeability layers enhance instability compared with thin layers when heterogeneity is increased.more » On the contrary, for thin layers the instability is weakened progressively with increasing heterogeneity to the extent that the corresponding homogeneous case is more unstable. For high levels of heterogeneity, we find that a small change in the permeability field results in large variations in the onset time of convection, similar to the instability event in the linear regime. However, this trend does not persist unconditionally because of the reorientation of vorticity pairs due to the interaction of evolving perturbation structures with heterogeneity. Consequently, an earlier onset of instability does not necessarily imply an earlier onset of convection. A resonant amplification of instability is observed within the linear regime when the dominant perturbation mode is equal to half the wavenumber of permeability variation. On the other hand, a substantial damping occurs when the perturbation mode is equal to the harmonic and sub-harmonic components of the permeability wavenumber. Finally, the phenomenon of such harmonic interactions influences both the onset of instability as well as the onset of convection.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ma, Tianran; Rutqvist, Jonny; Oldenburg, Curtis M.
This study presents the development and application of a fully coupled two-phase (methane and water) flow, transport, and poromechanics num erical model for the analysis of geomechanical impacts on coalbed methane (CBM) production. The model considers changes in two-phase fluid flow properties, i.e., coal porosity, permeability, water retention, and relative permeability curves through changes in cleat fractures induced by effective stress variations and desorption-induced shrinkage. The coupled simulator is first verified for poromechanics coupling, and simulation parameters of a CBM reservoir model are calibrated by history matching against one year of CBM production field data from Shanxi Province, China. Then,more » the verified simulator and the calibrated CBM reservoir model are used for predicting the impact of geomechanics on the production rate for twenty years of continuous CBM production. The simulation results show that desorption-induced shrinkage is the dominant process in increasing permeability in the near wellbore region. Away from the wellbore, desorption-induced shrinkage is weaker, and permeability is reduced by pressure depletion and increased effective stress. A sensitivity analysis shows that for coal with a higher sorption strain, a larger initial Young's modulus and a smaller Poisson's ratio promote the enhancement of permeability as well as an increased production rate. Moreover, the conceptual model of the cleat system, whether dominated by vertical cleats with permeability correlated to horizontal stress or with permeability correlated to mean stress, can have a significant impact on the predicted production rate. Overall, the study clearly demonstrates and confirms the critical importance of considering geomechanics for an accurate prediction of CBM production.« less
Song, Jie; Almasalmeh, Abdulnasser; Krenc, Dawid; Beitz, Eric
2012-05-01
The aquaglyceroporins of Escherichia coli, EcGlpF, and of Plasmodium falciparum, PfAQP, are probably the best characterized members of the solute-conducting aquaporin (AQP) subfamily. Their crystal structures have been elucidated and numerous experimental and theoretical analyses have been conducted. However, opposing reports on their rates of water permeability require clarification. Hence, we expressed EcGlpF and PfAQP in yeast, prepared protoplasts, and compared water and glycerol permeability of both aquaglyceroporins in the presence of different osmolytes, i.e. sucrose, sorbitol, PEG300, and glycerol. We found that water permeability of PfAQP strongly depends on the external osmolyte, with full inhibition by sorbitol, and increasing water permeability when glycerol, PEG300, and sucrose were used. EcGlpF expression did not enhance water permeability over that of non-expressing control protoplasts regardless of the osmolyte. Glycerol permeability of PfAQP was also inhibited by sorbitol, but to a smaller extent, whereas EcGlpF conducted glycerol independently of the osmolyte. Mixtures of glycerol and urea passed PfAQP equally well under isosmotic conditions, whereas under hypertonic conditions in a countercurrent with water, glycerol was clearly preferred over urea. We conclude that PfAQP has high and EcGlpF low water permeability, and explain the inhibiting effect of sorbitol on PfAQP by its binding to the extracellular vestibule. The preference for glycerol under hypertonic conditions implies that in a physiological setting, PfAQP mainly acts as a water/glycerol channel rather than a urea facilitator. Copyright © 2012 Elsevier B.V. All rights reserved.
Convective mixing in vertically-layered porous media: The linear regime and the onset of convection
Ghorbani, Zohreh; Riaz, Amir; Daniel, Don
2017-08-02
In this paper, we study the effect of permeability heterogeneity on the stability of gravitationally unstable, transient, diffusive boundary layers in porous media. Permeability is taken to vary periodically in the horizontal plane normal to the direction of gravity. In contrast to the situation for vertical permeability variation, the horizontal perturbation structures are multimodal. We therefore use a two-dimensional quasi-steady eigenvalue analysis as well as a complementary initial value problem to investigate the stability behavior in the linear regime, until the onset of convection. We find that thick permeability layers enhance instability compared with thin layers when heterogeneity is increased.more » On the contrary, for thin layers the instability is weakened progressively with increasing heterogeneity to the extent that the corresponding homogeneous case is more unstable. For high levels of heterogeneity, we find that a small change in the permeability field results in large variations in the onset time of convection, similar to the instability event in the linear regime. However, this trend does not persist unconditionally because of the reorientation of vorticity pairs due to the interaction of evolving perturbation structures with heterogeneity. Consequently, an earlier onset of instability does not necessarily imply an earlier onset of convection. A resonant amplification of instability is observed within the linear regime when the dominant perturbation mode is equal to half the wavenumber of permeability variation. On the other hand, a substantial damping occurs when the perturbation mode is equal to the harmonic and sub-harmonic components of the permeability wavenumber. Finally, the phenomenon of such harmonic interactions influences both the onset of instability as well as the onset of convection.« less
Dube, P J; Vanotti, M B; Szogi, A A; García-González, M C
2016-03-01
Gas-permeable membrane technology is useful to recover ammonia from manure. In this study, the technology was enhanced using aeration instead of alkali chemicals to increase pH and the ammonium (NH4(+)) recovery rate. Digested effluents from covered anaerobic swine lagoons containing 1465-2097 mg NH4(+)-N L(-1) were treated using submerged membranes (0.13 cm(2) cm(-3)), low-rate aeration (120 mL air L-manure(-1) min(-1)) and nitrification inhibitor (22 mg L(-1)) to prevent nitrification. The experiment included a control without aeration. The pH of the manure with aeration rose from 8.6 to 9.2 while the manure without aeration decreased from 8.6 to 8.1. With aeration, 97-99% of the NH4(+) was removed in about 5 days of operation with 96-98% recovery efficiency. In contrast, without aeration it took 25 days to treat the NH4(+). Therefore, the recovery of NH4(+) was five times faster with the low-rate aeration treatment. This enhancement could reduce costs by 70%. Published by Elsevier Ltd.
DOT National Transportation Integrated Search
2016-09-01
The Kansas Department of Transportation (KDOT) has a history of using : tests such as concrete strength, permeability, and air void structure as design : and acceptance criteria on concrete paving and bridge deck projects. In 2012, : the KDOT Concret...
Unraveling supported lipid bilayer formation kinetics: osmotic effects.
Hain, Nicole; Gallego, Marta; Reviakine, Ilya
2013-02-19
Solid-supported lipid bilayers are used as cell membrane models and form the basis of biomimetic and biosensor platforms. The mechanism of their formation from adsorbed liposomes is not well-understood. Using membrane-permeable solute glycerol, impermeable solutes sucrose and dextran, and a pore forming peptide melittin, we studied experimentally how osmotic effects affect the kinetics of the adsorbed liposome-to-bilayer transition. We find that its rate is enhanced if adsorbed liposomes are made permeable but is not significantly retarded by impermeable solutes. The results are explained in terms of adsorbed liposome deformation and formation of transmembrane pores.
Verification of capillary pressure functions and relative permeability equations for gas production
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jang, Jaewon
The understanding of multiphase fluid flow in porous media is of great importance in many fields such as enhanced oil recovery, hydrology, CO 2 sequestration, contaminants cleanup and natural gas production from hydrate bearing sediments. However, there are many unanswered questions about the key parameters that characterize gas and water flows in porous media. The characteristics of multiphase fluid flow in porous media such as water retention curve, relative permeability, preferential fluid flow patterns and fluid-particle interaction should be taken into consideration for a fundamental understanding of the behavior of pore scale systems.
Over-Expression of Arabidopsis EDT1 Gene Confers Drought Tolerance in Alfalfa (Medicago sativa L.)
Zheng, Guangshun; Fan, Cunying; Di, Shaokang; Wang, Xuemin; Xiang, Chengbin; Pang, Yongzhen
2017-01-01
Alfalfa (Medicago sativa L.) is an important legume forage crop with great economic value. However, as the growth of alfalfa is seriously affected by an inadequate supply of water, drought is probably the major abiotic environmental factor that most severely affects alfalfa production worldwide. In an effort to enhance alfalfa drought tolerance, we transformed the Arabidopsis Enhanced Drought Tolerance 1 (AtEDT1) gene into alfalfa via Agrobacterium-mediated transformation. Compared with wild type plants, drought stress treatment resulted in higher survival rates and biomass, but reduced water loss rates in the transgenic plants. Furthermore, transgenic alfalfa plants had increased stomatal size, but reduced stomatal density, and these stomatal changes contributed greatly to reduced water loss from leaves. Importantly, transgenic alfalfa plants exhibited larger root systems with larger root lengths, root weight, and root diameters than wild type plants. The transgenic alfalfa plants had reduced membrane permeability and malondialdehyde content, but higher soluble sugar and proline content, higher superoxide dismutase activity, higher chlorophyll content, enhanced expression of drought-responsive genes, as compared with wild type plants. Notably, transgenic alfalfa plants grew better in a 2-year field trial and showed enhanced growth performance with increased biomass yield. All of our morphological, physiological, and molecular analyses demonstrated that the ectopic expression of AtEDT1 improved growth and enhanced drought tolerance in alfalfa. Our study provides alfalfa germplasm for use in forage improvement programs, and may help to increase alfalfa production in arid lands. PMID:29326737
Over-Expression of Arabidopsis EDT1 Gene Confers Drought Tolerance in Alfalfa (Medicago sativa L.).
Zheng, Guangshun; Fan, Cunying; Di, Shaokang; Wang, Xuemin; Xiang, Chengbin; Pang, Yongzhen
2017-01-01
Alfalfa ( Medicago sativa L.) is an important legume forage crop with great economic value. However, as the growth of alfalfa is seriously affected by an inadequate supply of water, drought is probably the major abiotic environmental factor that most severely affects alfalfa production worldwide. In an effort to enhance alfalfa drought tolerance, we transformed the Arabidopsis Enhanced Drought Tolerance 1 ( AtEDT1 ) gene into alfalfa via Agrobacterium -mediated transformation. Compared with wild type plants, drought stress treatment resulted in higher survival rates and biomass, but reduced water loss rates in the transgenic plants. Furthermore, transgenic alfalfa plants had increased stomatal size, but reduced stomatal density, and these stomatal changes contributed greatly to reduced water loss from leaves. Importantly, transgenic alfalfa plants exhibited larger root systems with larger root lengths, root weight, and root diameters than wild type plants. The transgenic alfalfa plants had reduced membrane permeability and malondialdehyde content, but higher soluble sugar and proline content, higher superoxide dismutase activity, higher chlorophyll content, enhanced expression of drought-responsive genes, as compared with wild type plants. Notably, transgenic alfalfa plants grew better in a 2-year field trial and showed enhanced growth performance with increased biomass yield. All of our morphological, physiological, and molecular analyses demonstrated that the ectopic expression of AtEDT1 improved growth and enhanced drought tolerance in alfalfa. Our study provides alfalfa germplasm for use in forage improvement programs, and may help to increase alfalfa production in arid lands.
Sun, Chen; Hou, Jian; Pan, Guangming; Xia, Zhizeng
2016-01-01
A successful cross-linked polymer flooding has been implemented in JD reservoir, an ordinary heavy oil reservoir with high permeability zones. For all that, there are still significant volumes of continuous oil remaining in place, which can not be easily extracted due to stronger vertical heterogeneity. Considering selective plugging feature, polymer enhanced foam (PEF) flooding was taken as following EOR technology for JD reservoir. For low cost and rich source, natural gas was used as foaming gas in our work. In the former work, the surfactant systems CEA/FSA1 was recommended as foam agent for natural gas foam flooding after series of compatibility studies. Foam performance evaluation experiments showed that foaming volume reached 110 mL, half-life time reached 40 min, and dimensionless filter coefficient reached 1.180 when CEA/FSA1 reacted with oil produced by JD reservoir. To compare the recovery efficiency by different EOR technologies, series of oil displacement experiments were carried out in a parallel core system which contained cores with relatively high and low permeability. EOR technologies concerned in our work include further cross-linked polymer (C-P) flooding, surfactant-polymer (S-P) flooding, and PEF flooding. Results showed that PEF flooding had the highest enhanced oil recovery of 19.2 % original oil in place (OOIP), followed by S-P flooding (9.6 % OOIP) and C-P flooding (6.1 % OOIP). Also, produced liquid percentage results indicated PEF flooding can efficiently promote the oil recovery in the lower permeability core by modifying the injection profile.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Skrinnik, A.V.
The author attempts to obtain direct proof of increased permeability of the cornea and enhanced sorption properties of the tissue structures and refractive media of the eye under the influence of a pulsed magnetic field (MF). In the course of the investigation, the method of radioactive indication of two substances (/sup 35/S-streptomycin and /sup 75/Se-methionine), widely used in opthalmologic practice, was used. The radioactivity of the working solution of the preparations was 300,000 cpm in 0.1 ml. Changes in the permeability of the cornea were assessed on the basis of changes in radioactivity of the aqueous humor. The concentration ofmore » /sup 35/S-streptomycin in aqueous humor of the animals immediately after exposure to MF was significantly higher than in the control. Analysis of permeability of the cornea for /sup 75/Se-methionine also showed increased penetration of radioactivity into the aqueous. The results are evidence of the greater penetrating power of /sup 75/Se-methionine.« less
NASA Astrophysics Data System (ADS)
Li, Z. W.; Guoqing, Lin; Chen, Linfeng; Yuping, Wu; Ong, C. K.
2006-03-01
Co2+Ti4+ substitution for Fe3+ in Co2Z (Ba3Co2Fe24O41) has been prepared. The crystal structure and static and high-frequency magnetic properties have been studied for Ba3Co2+xTixFe24-2xO41 and the corresponding ferrite/polymer composites. As compared to the general Co2Z ferrite/polymer composite, the CoTi substituted ferrite/polymer composite with x=1.0 has a high natural resonance frequency (4.5 GHz), due to its large out-of-plane anisotropy fields Hθ. Furthermore, the maximum imaginary permeability μmax'' is increased by about 50%. The increase is attributed to a decreased damping coefficient, based on the curve-fitted results to the complex permeability spectra. The composites are good electromagnetic attenuation materials with low reflectivity and broad bandwidth at microwave frequencies.
NASA Astrophysics Data System (ADS)
Mann, Erin
Both industry and commercial entities are in the process of using more lightweight composites. Fillers, such as fibers, nanofibers and other nanoconstituents in polymer matrix composites have been proven to enhance the properties of composites and are still being studied in order to optimize the benefits. Further optimization can be studied during the manufacturing process. The air permeability during the out-of-autoclave-vacuum-bag-only (OOA-VBO) cure method is an important property to understand during the optimization of manufacturing processes. Changes in the manufacturing process can improve or decrease composite quality depending on the ability of the composite to evacuate gases such as air and moisture during curing. Therefore, in this study, the axial permeability of a prepreg stack was experimentally studied. Three types of samples were studied: control (no carbon nanofiber (CNF) modification), unaligned CNF modified and aligned CNF modified samples.
Sacher, Joseph A.; Salminen, Seppo O.
1969-01-01
The effects of ethylene on permeability and RNA and protein synthesis were assayed over a 6 to 26 hr period in tissue sections from avocado (Persea gratissima Gaertn. F., var. Fuerte), both pulp and peel of banana (Musa sapientum L., var. Gros Michel), bean endocarp (Phaseolus vulgaris L., var. Kentucky Wonder Pole beans) and leaves of Rhoeo discolor. Ethylene had no effect on permeability in 4 of the 5 tissues, but sometimes enhanced solute uptake in banana peel; it had either no effect or an inhibitory effect on synthesis of RNA and protein in sections from fruits of avocado and banana. Auxin (α-naphthalene acetic acid) stimulated synthesis of RNA and protein in bean endocarp and Rhoeo leaf sections, whereas ethylene inhibited both basal and auxin-induced synthesis. It is concluded that in these tissues the auxin effect is not an ethylene effect. PMID:16657212
Effect of drainage in unbound aggregate bases on flexible pavement performance.
DOT National Transportation Integrated Search
2008-05-01
It has been well demonstrated that a positive subsurface drainage is beneficial in enhancing pavement performance and thus extending pavement service life. Typical permeable base materials include asphalt/cement-treated, open-graded aggregates and un...
NASA Astrophysics Data System (ADS)
Vidal, J.; Genter, A.; Schmittbuhl, J.; Baujard, C.
2016-12-01
In the Upper Rhine Graben, several deep geothermal projects, such as at Soultz-sous-Forêts (France) or Basel (Switzerland), were based on the Enhanced Geothermal System technology. The principle underlying this technology consists of increasing the low initial natural hydraulic performance of pre-existing natural fractures in the geothermal granitic reservoir via hydraulic and/or chemical stimulations. Hydraulic stimulation consists of injection of a large amount of water at a high flow rate to promote hydroshearing of pre-existing fractures. At Soultz-sous-Forêts and Basel, the maximum wellhead pressures were 16 MPa and 30 MPa respectively which induced larger magnitude seismic events of 2.9 and 3.4 respectively. Those specific induced seismicity events were felt by local population. At Rittershoffen (France), the geothermal well GRT-1 was drilled in 2012 down to a depth of 2.6 km and penetrates fractured sandstones and granite. The reservoir temperature reaches more than 160°C but the production flowrate was too low for an industrial project economically viable. Thus, the well was subjected to Thermal, Chemical and Hydraulic stimulations, which improved the injectivity index five-fold. During the hydraulic operation, a moderate volume of water was injected from the wellhead with a low pressure of 3 MPa. Approximately 300 microseismic events were detected during the hydraulic stimulations. Due to the low wellhead pressure during injection, no events were felt by nearby residents. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation acoustic image logs. This comparison revealed minor modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement. The most important permeability enhancement was observed on the originally permeable fault zone affecting the top of the granitic basement. In the Upper Rhine Graben, several deep geothermal projects, such as at Soultz-sous-Forêts (France) or Basel (Switzerland), were based on the Enhanced Geothermal System technology. The principle underlying this technology consists of increasing the low initial natural hydraulic performance of pre-existing natural fractures in the geothermal granitic reservoir via hydraulic and/or chemical stimulations. Hydraulic stimulation consists of injection of a large amount of water at a high flow rate to promote hydroshearing of pre-existing fractures. At Soultz-sous-Forêts and Basel, the maximum wellhead pressures were 16 MPa and 30 MPa respectively which induced larger magnitude seismic events of 2.9 and 3.4 respectively. Those specific induced seismicity events were felt by local population. At Rittershoffen (France), the geothermal well GRT-1 was drilled in 2012 down to a depth of 2.6 km and penetrates fractured sandstones and granite. The reservoir temperature reaches more than 160°C but the production flowrate was too low for an industrial project economically viable. Thus, the well was subjected to Thermal, Chemical and Hydraulic stimulations, which improved the injectivity index five-fold. During the hydraulic operation, a moderate volume of water was injected from the wellhead with a low pressure of 3 MPa. Approximately 300 microseismic events were detected during the hydraulic stimulations. Due to the low wellhead pressure during injection, no events were felt by nearby residents. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation acoustic image logs. This comparison revealed minor modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement. The most important permeability enhancement was observed on the originally permeable fault zone affecting the top of the granitic basement.
Composite Crew Module (CCM) Permeability Characterization
NASA Technical Reports Server (NTRS)
Kirsch, Michael T.
2013-01-01
In January 2007, the NASA Administrator chartered the NASA Engineering and Safety Center (NESC) to form an Agency team to design and build a composite crew module in 18 months in order to gain hands-on experience in anticipation that future exploration systems may be made of composite materials. One of the conclusions from this Composite Crew Module Primary Structure assessment was that there was a lack of understanding regarding the ability for composite pressure shells to contain consumable gases, which posed a technical risk relative to the use of a metallic design. After the completion of the Composite Crew Module test program, the test article was used in a new program to assess the overall leakage/permeability and identify specific features associated with high leak rates. This document contains the outcome of the leakage assessment.
Cost studies of thermally enhanced in situ soil remediation technologies
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bremser, J.; Booth, S.R.
1996-05-01
This report describes five thermally enhanced technologies that may be used to remediate contaminated soil and water resources. The standard methods of treating these contaminated areas are Soil Vapor Extraction (SVE), Excavate & Treat (E&T), and Pump & Treat (P&T). Depending on the conditions at a given site, one or more of these conventional alternatives may be employed; however, several new thermally enhanced technologies for soil decontamination are emerging. These technologies are still in demonstration programs which generally are showing great success at achieving the expected remediation results. The cost savings reported in this work assume that the technologies willmore » ultimately perform as anticipated by their developers in a normal environmental restoration work environment. The five technologies analyzed in this report are Low Frequency Heating (LF or Ohmic, both 3 and 6 phase AC), Dynamic Underground Stripping (DUS), Radio Frequency Heating (RF), Radio Frequency Heating using Dipole Antennae (RFD), and Thermally Enhanced Vapor Extraction System (TEVES). In all of these technologies the introduction of heat to the formation raises vapor pressures accelerating contaminant evaporation rates and increases soil permeability raising diffusion rates of contaminants. The physical process enhancements resulting from temperature elevations permit a greater percentage of volatile organic compound (VOC) or semi- volatile organic compound (SVOC) contaminants to be driven out of the soils for treatment or capture in a much shorter time period. This report presents the results of cost-comparative studies between these new thermally enhanced technologies and the conventional technologies, as applied to five specific scenarios.« less
Wang, Dan; Wang, Ming-Liang; Li, Yue-Hua
2017-08-15
To use Ktrans to evaluate the aggressiveness and vascular permeability of peritumoral edema in cases of lung cancer brain metastases. A total of 68 lung cancer patients with 92 metastatic brain lesions were enrolled (20 metastatic lesions only in the gray matter - group 1; and 72 metastatic lesions located in the gray and white matter junction - group 2). All patients underwent MRI examination, which involved a dual angle (2° and 15°) enhanced T1W-VIBE (volume interpolated breath-hold examination) sequence to calculate the T1 parameter map. We used the enhanced T1-3D sequence to measure the tumor volume. The vascular permeability coefficient (Ktrans) was calculated using the single-compartment Tofts model, motion registration, and quick input mode. We examined the correlations of Ktrans with the edema index (EI), Ktrans with the tumor volume, and Ktrans with the histological expression of MMP-9 or VEGF in the original lung tumor using Pearson's' correlation analysis. Ktrans and EI were highly correlated in group 2 (r=0.66687; P<0.001) and not correlated in group 1 (r=0.33096; P=0.15405). Ktrans was also moderately related to the positive expression of MMP-9 (r=0.50912; P<0.001) and VEGF (r=0.36995; P=0.00138) There is statistical correlation between Ktrans and EI for group 2, and no statistical correlation between Ktrans and EI for group 1. The Ktrans of the peritumoral brain edema may be used to indicate the aggressiveness and vascular permeability of brain metastases in patients with lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.
Zeise, Brian; Xu, Danyun; Rappel, Wouter-Jan; Boron, Walter F.; Schroeder, Julian I.
2016-01-01
Dark respiration causes an increase in leaf CO2 concentration (Ci), and the continuing increases in atmospheric [CO2] further increases Ci. Elevated leaf CO2 concentration causes stomatal pores to close. Here, we demonstrate that high intracellular CO2/HCO3− enhances currents mediated by the Arabidopsis thaliana guard cell S-type anion channel SLAC1 upon coexpression of any one of the Arabidopsis protein kinases OST1, CPK6, or CPK23 in Xenopus laevis oocytes. Split-ubiquitin screening identified the PIP2;1 aquaporin as an interactor of the βCA4 carbonic anhydrase, which was confirmed in split luciferase, bimolecular fluorescence complementation, and coimmunoprecipitation experiments. PIP2;1 exhibited CO2 permeability. Mutation of PIP2;1 in planta alone was insufficient to impair CO2- and abscisic acid-induced stomatal closing, likely due to redundancy. Interestingly, coexpression of βCA4 and PIP2;1 with OST1-SLAC1 or CPK6/23-SLAC1 in oocytes enabled extracellular CO2 enhancement of SLAC1 anion channel activity. An inactive PIP2;1 point mutation was identified that abrogated water and CO2 permeability and extracellular CO2 regulation of SLAC1 activity. These findings identify the CO2-permeable PIP2;1 as key interactor of βCA4 and demonstrate functional reconstitution of extracellular CO2 signaling to ion channel regulation upon coexpression of PIP2;1, βCA4, SLAC1, and protein kinases. These data further implicate SLAC1 as a bicarbonate-responsive protein contributing to CO2 regulation of S-type anion channels. PMID:26764375
Jain, Ritesh; Agarwal, Sheetal; Mandava, Nanda Kishore; Sheng, Ye; Mitra, Ashim K
2008-10-01
Saquinavir (SQV), the first protease inhibitor approved by FDA to treat HIV-1 infection. This drug is a well-known substrate for multidrug resistance protein-2 (MRP-2). The objective of this study was to investigate whether derivatization of SQV to dipeptide prodrugs, valine-valine-saquinavir (Val-Val-SQV) and glycine-valine-saquinavir (Gly-Val-SQV), targeting peptide transporter can circumvent MRP-2 mediated efflux. Uptake and transport studies were carried out across MDCKII-MRP2 cell monolayers to investigate the interaction of SQV and its prodrugs with MRP-2. In situ single pass intestinal perfusion experiments in rat jejunum were performed to calculate intestinal absorption rate constants and permeabilities of SQV, Val-Val-SQV and Gly-Val-SQV. Uptake studies demonstrated that the prodrugs have significantly lower interaction with MRP-2 relative to SQV. Transepithelial transport of Val-Val-SQV and Gly-Val-SQV across MDCKII-MRP2 cells exhibited an enhanced absorptive flux and reduced secretory flux as compared to SQV. Intestinal perfusion studies revealed that synthesized prodrugs have higher intestinal permeabilities relative to SQV. Enhanced absorption of Val-Val-SQV and Gly-Val-SQV relative to SQV can be attributed to their translocation by the peptide transporter in the jejunum. In the presence of MK-571, a MRP family inhibitor, there was a significant increase in the permeabilities of SQV and Gly-Val-SQV indicating that these compounds are probably substrates for MRP-2. However, there was no change in the permeability of Val-Val-SQV with MK-571 indicating lack of any interaction of Val-Val-SQV with MRP-2. In conclusion, peptide transporter targeted prodrug modification of MRP-2 substrates may lead to shielding of these drug molecules from MRP-2 efflux pumps.
Garg, Anuj; Bhalala, Kripal; Tomar, Devendra Singh; Wahajuddin
2017-01-10
The present investigation aims to develop lumefantrine loaded binary solid lipid nanoparticles (LF-SLNs) to improve its poor and variable oral bioavailability. The oral bioavailability of LF is poor and variable due to its limited aqueous solubility and P-gp mediated efflux occurring in small intestine. LF-SLNs were prepared using binary lipid mixture of stearic acid and caprylic acid stabilized with TPGS (D-alpha tocopheryl polyethylene glycol 1000 succinate) and Poloxamer 188. Developed LF-SLNs were characterized for particle size distribution, zeta potential, entrapment efficiency, solid state properties and biopharmaceutical properties including in situ intestinal permeability and oral bioavailability. The particle size distribution, zeta potential and entrapment efficiency of optimized batch (LF-SLN7) was found to be 357.7±43.27nm, 25.29±1.15mV and 97.35±0.30%, respectively. DSC thermographs showed loss of crystalline nature of lumefantrine in LF-SLNs. In situ single pass intestinal permeability study (SPIP) study indicated significant enhancement in the effective intestinal permeability of LF from LF-SLN7 as compared to that of control. Pharmacokinetic study also showed significant increase in Cmax and area under curve (AUC0- ∞ ) from LF-SLN7 (3860±521ng/mL and 43181±2557h×ng/mL, respectively) as compared to that of LF-control suspension (1425±563ng/mL and 19586±1537h×ng/mL, respectively). Thus, developed LF-SLNs can be promising to overcome P-gp efflux pump and enhance the oral bioavailability of lumefantrine. Copyright © 2016 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Mitchell, T. M.; Faulkner, D. R.
2009-04-01
Models predicting crustal fluid flow are important for a variety of reasons; for example earthquake models invoking fluid triggering, predicting crustal strength modelling flow surrounding deep waste repositories or the recovery of natural resources. Crustal fluid flow is controlled by both the bulk transport properties of rocks as well as heterogeneities such as faults. In nature, permeability is enhanced in the damage zone of faults, where fracturing occurs on a wide range of scales. Here we analyze the contribution of microfracture damage on the permeability of faults that cut through low porosity, crystalline rocks by combining field and laboratory measurements. Microfracture densities surrounding strike-slip faults with well-constrained displacements ranging over 3 orders of magnitude (~0.12 m - 5000 m) have been analyzed. The faults studied are excellently exposed within the Atacama Fault Zone, where exhumation from 6-10 km has occurred. Microfractures in the form of fluid inclusion planes (FIPs) show a log-linear decrease in fracture density with perpendicular distance from the fault core. Damage zone widths defined by the density of FIPs scale with fault displacement, and an empirical relationship for microfracture density distribution throughout the damage zone with displacement is derived. Damage zone rocks will have experienced differential stresses that were less than, but some proportion of, the failure stress. As such, permeability data from progressively loaded, initially intact laboratory samples, in the pre-failure region provide useful insights into fluid flow properties of various parts of the damage zone. The permeability evolution of initially intact crystalline rocks under increasing differential load leading to macroscopic failure was determined at water pore pressures of 50 MPa and effective pressure of 10 MPa. Permeability is seen to increase by up to, and over, two orders of magnitude prior to macroscopic failure. Further experiments were stopped at various points in the loading history in order to correlate microfracture density within the samples with permeability. By combining empirical relationships determined from both quantitative fieldwork and experiments we present a new model that allows microfracture permeability distribution throughout the damage zone to be determined as function of increasing fault displacement.
NASA Astrophysics Data System (ADS)
Cheng, J.; Johnson, B.; Everett, M.
2003-12-01
Preliminary field work shows slug interference tests using an array of multilevel active and monitoring wells have potential of permitting enhanced aquifer characterization. Analysis of these test data, however, ultimately will rely on numerical geophysical inverse models. In order to gain insight as well as to provide synthetic data sets, we use a 3-D finite element analysis (code:FEHM-LANL) to explore the effect of idealized, low permeability, stratigraphical and structural (faults) heterogeneities on the transient head field associated with a slug test in a packer-isolated interval of an open borehole. The borehole and packers are modeled explicitly; wellbore storage is selected to match values of field tests. The homogeneous model exhibits excellent agreement with that of the semi-analytical model of Liu and Butler (1995). Models are axisymmetric with a centrally located slugged interval within a homogenous, isotropic, confined aquifer with embedded, horizontal or vertical zones of lower permeability that represent low permeability strata or faults, respectively. Either one or two horizontal layers are located opposite the borehole packers, which is a common situation at the field site; layer thickness (0.15-0.75 m), permeability contrast (up to 4 orders of magnitude contrast) and lateral continuity of layers are varied between models. The effect of a "hole" in a layer also is assessed. Fault models explore effects of thickness (0.05-0.75 m) and permeability contrast as well as additional effects associated with the offset of low permeability strata. Results of models are represented most clearly by contour maps of time of arrival and normalized amplitude of peak head perturbation, but transient head histories at selected locations provide additional insight. Synthesis of the models is on-going but a few points can be made at present. Spatial patterns are distinctive and allow easy discrimination between stratigraphic and structural impedance features. Time delays and amplitude reduction increase nonlinearly with increasing permeability contrast. The capacity to discriminate the effect of layer thickness decreases as permeability contrast increases.
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.
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
NASA Astrophysics Data System (ADS)
Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C.; Konofagou, Elisa E.
2015-12-01
Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n = 60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r2 = 0.77) (2) the permeability of the opened BBB (r2 = 0.82) (3) the likelihood of safe opening (P < 0.05, safe opening compared to cases of damage; P < 0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r2 = 0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions.
Willenbring, Robin C; Jin, Fang; Hinton, David J; Hansen, Mike; Choi, Doo-Sup; Pavelko, Kevin D; Johnson, Aaron J
2016-08-31
CD8 T cell-mediated blood-brain barrier (BBB) disruption is dependent on the effector molecule perforin. Human perforin has extensive single nucleotide variants (SNVs), the significance of which is not fully understood. These SNVs can result in reduced, but not ablated, perforin activity or expression. However, complete loss of perforin expression or activity results in the lethal disease familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). In this study, we address the hypothesis that a single perforin allele can alter the severity of BBB disruption in vivo using a well-established model of CNS vascular permeability in C57Bl/6 mice. The results of this study provide insight into the significance of perforin SNVs in the human population. We isolated the effect a single perforin allele has on CNS vascular permeability through the use of perforin-heterozygous (perforin+/-) C57BL/6 mice in the peptide-induced fatal syndrome (PIFS) model of immune-mediated BBB disruption. Seven days following Theiler's murine encephalomyelitis virus (TMEV) CNS infection, neuroinflammation and TMEV viral control were assessed through flow cytometric analysis and quantitative real-time PCR of the viral genome, respectively. Following immune-mediated BBB disruption, gadolinium-enhanced T1-weighted MRI, with 3D volumetric analysis, and confocal microscopy were used to define CNS vascular permeability. Finally, the open field behavior test was used to assess locomotor activity of mice following immune-mediated BBB disruption. Perforin-null mice had negligible CNS vascular permeability. Perforin-WT mice have extensive CNS vascular permeability. Interestingly, perforin-heterozygous mice had an intermediate level of CNS vascular permeability as measured by both gadolinium-enhanced T1-weighted MRI and fibrinogen leakage in the brain parenchyma. Differences in BBB disruption were not a result of increased CNS immune infiltrate. Additionally, TMEV was controlled in a perforin dose-dependent manner. Furthermore, a single perforin allele is sufficient to induce locomotor deficit during immune-mediated BBB disruption. Perforin modulates BBB disruption in a dose-dependent manner. This study demonstrates a potentially advantageous role for decreased perforin expression in reducing BBB disruption. This study also provides insight into the effect SNVs in a single perforin allele could have on functional deficit in neurological disease.
Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C; Konofagou, Elisa E
2015-12-07
Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n = 60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r(2) = 0.77); (2) the permeability of the opened BBB (r(2) = 0.82); (3) the likelihood of safe opening (P < 0.05, safe opening compared to cases of damage; P < 0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r(2) = 0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions.
NASA Astrophysics Data System (ADS)
Ulven, Ole Ivar; Sun, WaiChing
2016-04-01
Fluid transport in a porous medium has important implications for understanding natural geological processes. At a sufficiently large scale, a fluid-saturated porous medium can be regarded as a two-phase continuum, with the fluid constituent flowing in the Darcian regime. Nevertheless, a fluid mediated chemical reaction can in some cases change the permeability of the rock locally: Mineral dissolution can cause increased permeability, whereas mineral precipitation can reduce the permeability. This might trigger a complicated hydro-chemo-mechanical coupling effect that causes channeling of fluids or clogging of the system. If the fluid is injected or produced at a sufficiently high rate, the pressure might increase enough to cause the onset and propagation of fractures. Fractures in return create preferential flow paths that enhance permeability, localize fluid flow and chemical reaction, prevent build-up of pore pressure and cause anisotropy of the hydro-mechanical responses of the effective medium. This leads to a complex coupled process of solid deformation, chemical reaction and fluid transport enhanced by the fracture formation. In this work, we develop a new coupled numerical model to study the complexities of feedback among fluid pressure evolution, fracture formation and permeability changes due to a chemical process in a 2D system. We combine a discrete element model (DEM) previously used to study a volume expanding process[1, 2] with a new fluid transport model based on poroelasticity[3] and a fluid-mediated chemical reaction that changes the permeability of the medium. This provides new insights into the hydro-chemo-mechanical process of a transforming porous medium. References [1] Ulven, O. I., Storheim, H., Austrheim, H., and Malthe-Sørenssen, A. "Fracture Initiation During Volume Increasing Reactions in Rocks and Applications for CO2 Sequestration", Earth Planet. Sc. Lett. 389C, 2014a, pp. 132 - 142, doi:10.1016/j.epsl.2013.12.039. [2] Ulven, O. I., Jamtveit, B., and Malthe-Sørenssen, A., "Reaction-driven fracturing of porous rock", J. Geophys. Res. Solid Earth 119, 2014b, doi:10.1002/2014JB011102. [3] Ulven, O. I., and Sun, W.C., "A locally mass-conserving dual-graph lattice model for fluid-driven fracture", in prep.
NASA Astrophysics Data System (ADS)
Ding, M.; Hjelm, R.; Sussman, A. J.
2016-12-01
Low-permeability geomedia are prevalent in subsurface environments. They have become increasingly important in a wide range of applications such as CO2-sequestration, hydrocarbon recovery, enhanced geothermal systems, legacy waste stewardship, high-level radioactive waste disposal, and global security. The flow and transport characteristics of low-permeability geomedia are dictated by their exceedingly low permeability values ranging from 10-6 to 10-12 darcy with porosities dominated by nanoscale pores. Developing new characterization methods and robust computational models that allow estimation of transport properties of low-permeability geomedia has been identified as a critical basic research and technology development need for controlling subsurface and fluids flow. Due to its sensibility to hydrogen and flexible sample environment, neutron based elastic and inelastic scattering can, through various techniques, interrogate all the nanoscale pores in the sample whether they are fluid accessible or not, and readily characterize interfacial waters. In this presentation, we will present two studies revealing the effects of nanoscale pore confinement on fluid dynamics in geomedia. In one study, we use combined (ultra-small)/small-angle elastic neutron scatterings to probe nanoporous features responses in geological materials to transport processes. In the other study, incoherent inelastic neutron scattering was used to distingwish between intergranular pore water and fluid inclusion moisture in bedded rock salt, and to explore their thermal stablibility. Our work demonstrates that neutron based elastic and inelastic scatterings are techniques of choice for in situ probing hydrocarbon and water behavior in nanoporous materials, providing new insights into water-rock interaction and fluids transport in low-permeability geomaterials.
Fox, Don T.; Guo, Luanjing; Fujita, Yoshiko; ...
2015-12-17
Formation of mineral precipitates in the mixing interface between two reactant solutions flowing in parallel in porous media is governed by reactant mixing by diffusion and dispersion and is coupled to changes in porosity/permeability due to precipitation. The spatial and temporal distribution of mixing-dependent precipitation of barium sulfate in porous media was investigated with side-by-side injection of barium chloride and sodium sulfate solutions in thin rectangular flow cells packed with quartz sand. The results for homogeneous sand beds were compared to beds with higher or lower permeability inclusions positioned in the path of the mixing zone. In the homogeneous andmore » high permeability inclusion experiments, BaSO 4 precipitate (barite) formed in a narrow deposit along the length and in the center of the solution–solution mixing zone even though dispersion was enhanced within, and downstream of, the high permeability inclusion. In the low permeability inclusion experiment, the deflected BaSO 4 precipitation zone broadened around one side and downstream of the inclusion and was observed to migrate laterally toward the sulfate solution. A continuum-scale fully coupled reactive transport model that simultaneously solves the nonlinear governing equations for fluid flow, transport of reactants and geochemical reactions was used to simulate the experiments and provide insight into mechanisms underlying the experimental observations. Lastly, migration of the precipitation zone in the low permeability inclusion experiment could be explained by the coupling effects among fluid flow, reactant transport and localized mineral precipitation reaction.« less
David Jebaraj, D; Utsumi, Hideo; Milton Franklin Benial, A
2018-04-01
Low-frequency electron spin resonance studies were performed for 2 mM concentration of deuterated permeable and impermeable nitroxyl spin probes, 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl and 3-carboxy-2,2,5,5,-tetramethyl-1-pyrrolidinyloxy in pure water and various concentrations of corn oil solution. The electron spin resonance parameters such as the line width, hyperfine coupling constant, g factor, rotational correlation time, permeability, and partition parameter were estimated. The broadening of line width was observed for nitroxyl radicals in corn oil mixture. The rotational correlation time increases with increasing concentration of corn oil, which indicates the less mobile nature of spin probe in corn oil mixture. The membrane permeability and partition parameter values were estimated as a function of corn oil concentration, which reveals that the nitroxyl radicals permeate equally into the aqueous phase and oil phase at the corn oil concentration of 50%. The electron spin resonance spectra demonstrate the permeable and impermeable nature of nitroxyl spin probes. From these results, the corn oil concentration was optimized as 50% for phantom studies. In this work, the corn oil and pure water mixture phantom models with various viscosities correspond to plasma membrane, and whole blood membrane with different hematocrit levels was studied for monitoring the biological characteristics and their interactions with permeable nitroxyl spin probe. These results will be useful for the development of electron spin resonance and Overhauser-enhanced magnetic resonance imaging modalities in biomedical applications. Copyright © 2017 John Wiley & Sons, Ltd.
NASA Astrophysics Data System (ADS)
Jiang, F.; Tsuji, T.
2017-01-01
Given the world's growing demand for energy, a combination of geological CO2 sequestration and enhanced oil recovery (EOR) technologies is currently regarded as a promising solution, as it would provide a means of reducing carbon emissions into the atmosphere while also leading to the economic benefit of simultaneously recovering oil. The optimization of injection strategies to maximize CO2 storage and increase the oil recovery factors requires complicated pore-scale flow information within a reservoir system consisting of coexisting oil, water, and CO2 phases. In this study, an immiscible three-phase lattice-Boltzmann (LB) model was developed to investigate the complicated flow state with interaction between water, oil, and CO2 systems in porous media. The two main mechanisms of oil remobilization, namely, double-drainage and film flow, can be captured by our model. The estimation of three-phase relative permeability is proposed using the digital rock physics (DRP) simulations. The results indicate that the relative permeability of CO2 as calculated using our steady state method is not sensitive to the initial oil fraction if the oil distribution is originally uniform. Baker's (1988) empirical model was tested and found to be able to provide a good prediction of the three-phase relative permeability data. Our numerical method provides a new tool for accurately predicting three-phase relative permeability data directly based on micro-CT rock images.
Membranes of Polymers of Intrinsic Microporosity (PIM-1) Modified by Poly(ethylene glycol).
Bengtson, Gisela; Neumann, Silvio; Filiz, Volkan
2017-06-05
Until now, the leading polymer of intrinsic microporosity PIM-1 has become quite famous for its high membrane permeability for many gases in gas separation, linked, however, to a rather moderate selectivity. The combination with the hydrophilic and low permeable poly(ethylene glycol) (PEG) and poly(ethylene oxides) (PEO) should on the one hand reduce permeability, while on the other hand enhance selectivity, especially for the polar gas CO₂ by improving the hydrophilicity of the membranes. Four different paths to combine PIM-1 with PEG or poly(ethylene oxide) and poly(propylene oxide) (PPO) were studied: physically blending, quenching of polycondensation, synthesis of multiblock copolymers and synthesis of copolymers with PEO/PPO side chain. Blends and new, chemically linked polymers were successfully formed into free standing dense membranes and measured in single gas permeation of N₂, O₂, CO₂ and CH₄ by time lag method. As expected, permeability was lowered by any substantial addition of PEG/PEO/PPO regardless the manufacturing process and proportionally to the added amount. About 6 to 7 wt % of PEG/PEO/PPO added to PIM-1 halved permeability compared to PIM-1 membrane prepared under similar conditions. Consequently, selectivity from single gas measurements increased up to values of about 30 for CO₂/N₂ gas pair, a maximum of 18 for CO₂/CH₄ and 3.5 for O₂/N₂.
Critical dynamics of gravito-convective mixing in geological carbon sequestration
Soltanian, Mohamad Reza; Amooie, Mohammad Amin; Dai, Zhenxue; ...
2016-11-03
When CO 2 is injected in saline aquifers, dissolution causes a local increase in brine density that can cause Rayleigh-Taylor-type gravitational instabilities. Depending on the Rayleigh number, density-driven flow may mix dissolved CO 2 throughout the aquifer at fast advective time-scales through convective mixing. Heterogeneity can impact density-driven flow to different degrees. Zones with low effective vertical permeability may suppress fingering and reduce vertical spreading, while potentially increasing transverse mixing. In more complex heterogeneity, arising from the spatial organization of sedimentary facies, finger propagation is reduced in low permeability facies, but may be enhanced through more permeable facies. The connectivitymore » of facies is critical in determining the large-scale transport of CO 2-rich brine. We perform high-resolution finite element simulations of advection-diffusion transport of CO 2 with a focus on facies-based bimodal heterogeneity. Permeability fields are generated by a Markov Chain approach, which represent facies architecture by commonly observed characteristics such as volume fractions. CO 2 dissolution and phase behavior are modeled with the cubic-plus-association equation-of-state. Our results show that the organization of high-permeability facies and their connectivity control the dynamics of gravitationally unstable flow. Lastly, we discover new flow regimes in both homogeneous and heterogeneous media and present quantitative scaling relations for their temporal evolution.« less
DEMONSTRATION BULLETIN: HYDRAULIC FRACTURING OF CONTAMINATED SOIL
Hydraulic fracturing is a physical process that creates fractures in silty clay soil to enhance its permeability. The technology, developed by the Risk Reduction Engineering Laboratory (RREL) and the University of Cincinnati, creates sand-filled horizontal fractures up to 1 in. i...
IITRI RADIO FREQUENCY HEATING TECHNOLOGY - INNOVATIVE TECHNOLOGY EVALUATION REPORT
IITRI's patented in situ RFH technology enhances the removal of volatile and semi-volatile organics by soil vapor extraction (SVE). Electromagnetic energy heats the soil resulting in increased contaminant vapor pressures and potentially higher soil permeability. RFH heats soil us...
Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement
NASA Astrophysics Data System (ADS)
Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant
2013-03-01
Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.
Shiraishi, Kouichi; Harada, Yoshiko; Kawano, Kumi; Maitani, Yoshie; Hori, Katsuyoshi; Yanagihara, Kazuyoshi; Takigahira, Misato; Yokoyama, Masayuki
2012-01-01
To evaluate effect of a vascular disrupting agent, a combretastatin derivative (Cderiv), on tumor targeting for polymeric micelle carrier systems, containing either a diagnostic MRI contrast agent or a therapeutic anticancer drug. Cderiv was pre-administered 72 h before polymeric micelle MRI contrast agent injection. Accumulation of the MRI contrast agent in colon 26 murine tumor was evaluated with or without pretreatment of Cderiv by ICP and MRI. Significantly higher accumulation of the MRI contrast agent was found in tumor tissues when Cderiv was administered at 72 h before MRI contrast agent injection. T(1)-weighted images of the tumor exhibited substantial signal enhancement in tumor area at 24 h after the contrast agent injection. In T(1)-weighted images, remarkable T(1)-signal enhancements were observed in part of tumor, not in whole tumor. These results indicate that Cderiv pretreatment considerably enhanced the permeability of the tumor blood vessels. Antitumor activity of adriamycin encapsulated polymeric micelles with the Cderiv pretreatment suppressed tumor growth in 44As3 human gastric scirrhous carcinoma-bearing nude mice. Pretreatment of Cderiv enhanced tumor permeability, resulting in higher accumulation of polymeric micelle carrier systems in solid tumors.
Effect of pH on skin permeation enhancement of acidic drugs by l-menthol-ethanol system.
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.
Understanding the Effect of Biomineralization on Subsurface Injection Processes
NASA Astrophysics Data System (ADS)
Zamani, A.; Montoya, B.; Gabr, M.
2017-12-01
Microbial induced calcium carbonate precipitation (MICP) is a natural soil improvement technique. The calcium carbonate cementation increases the soil's shear strength, stiffness, and dilative tendencies; however, it may also reduce the permeability of the soil due to the reduction in pore space. Reduction in permeability can lead to an increase in treatment injection pressures or decrease in injection distance. Therefore, an investigation of the extent of permeability reduction is necessary to understand the effect on in situ injection procedures. A suite of soil column experiments were conducted on clean loose silica sand and loose silty sand (i.e., 15% non-plastic silt) by inducing MICP to incrementally higher levels of biomineralization (e.g., from an untreated state to a moderately cemented state for each soil type). The level of biomineralization was assessed using shear wave velocity measurements. Once the target levels of shear wave velocity were reached, the MICP treatments were terminated, and constant head permeability tests were conducted. The experimental results provided a relationship between permeability reduction and level of biomineralization. Upon completion of the permeability tests, the calcium carbonate minerals were evaluated with scanning electron microscopy and the distribution of cementation along the soil column height was assessed using gravimetric acid washing. The changes in permeability are upscaled towards in situ treatment by evaluating the resulting changes in allowable injection rate and radius of influence due to the MICP implementation by numerically modeling the groundwater flow using the finite element programs Seep/W and Sigma/W. The numerical results indicate the allowable injection rate and radius of influence are affected by both the reduction in permeability and the increase in stiffness from the MICP process. The injection simulations with clean sand indicate the reduction of permeability is overshadowed by the increase in stiffness of the material, and the allowable injection rate can increase as biomineralization occurs. However, the injection simulations with silty sand indicate the increase in stiffness compensates for the reduction in permeability, and allowable injection rate remains constant during the treatment.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bowers, B.; Rossabi, J.; Shinn, J.D. II
1997-05-01
This report documents the results of a combined field and laboratory investigation program to: (1) delineate the geologic layering and (2) determine the location of a dense non-aqueous liquid-phase (DNAPL) contaminated plume beneath the M Area Hazardous Waste Management Facility at the Savannah River Plant. During April of 1991, DNAPLs were detected in monitoring well (MSB-3D), located adjacent to the capped M-Area Settling Basin. Solvents in the well consisted mainly of tetrachloroethylene and trichloroethylene, which are also the main solvents found in groundwater in the M Area. In permeable soils, DNAPLs move downward rapidly due to their high density andmore » low viscosity as compared to water. Within the vadose zone, DNAPLs tend to be held by the less permeable clay and silts by capillary force. In the saturated zone, the downward movement is slowed by clays and silts and the DNAPL tends to pool on this layer, then spread laterally. The lateral movement continues until a permeable layer is encountered, which can be a sand lens, fracture or other high conductivity seam. The DNAPL then moves downward, until another low permeability layer is encountered. Applied Research Associates was contracted to conduct a program to: (1) field demonstrate the utility of Cone Penetration Technology to investigate DOE contaminant sites and, (2) conduct a laboratory and field program to evaluate the use of electric resistivity surveys to locate DNAPL contaminated soils. The field program was conducted in the M-Basin and laboratory tests were conducted on samples from the major stratigraphy units as identified in Eddy et. al. Cone Penetration Technology was selected to investigate the M-Basin as it: (1) is minimally invasive, (2) generates minimal waste, (3) is faster and less costly than drilling, (4) provides continuous, detailed in situ characterization data, (5) permits real-time data processing, and (6) can obtain soil, soil gas, and water samples without the need for a boring.« less
Luo, Shuanghui; Wang, Zhiying; Patel, Mitesh; Khurana, Varun; Zhu, Xiaodong; Pal, Dhananjay; Mitra, Ashim. K.
2015-01-01
In order to improve oral absorption, a novel prodrug of saquinavir (Saq), ascorbyl-succinic-saquinavir (AA-Su-Saq) targeting sodium dependent vitamin C transporter (SVCT) was synthesized and evaluated. Aqueous solubility, stability and cytotoxicity were determined. Affinity of AA-Su-Saq towards effluxpump P-glycoprotein (P-gp) and recognition of AA-Su-Saq by SVCT were studied. Transepithelial permeability across polarized MDCK-MDR1 and Caco-2 cells were determined. Metabolic stability of AA-Su-Saq in rat liver microsomes was investigated. AA-Su-Saq appears to be fairly stable in both DPBS and Caco-2 cells with half lives of 9.65 and 5.73 h, respectively. Uptake of [3H]Saquinavir accelerated by 2.7 and 1.9 fold in the presence of 50 μM Saq and AA-Su-Saq in MDCK-MDR1 cells. Cellular accumulation of [14C]AA diminished by about 50–70% relative to control in the presence of 200 μM AA-Su-Saq in MDCK-MDR1 and Caco-2 cells. Uptake of AA-Su-Saq was lowered by 27% and 34% in the presence of 5 mM AA in MDCK-MDR1 and Caco-2 cells, respectively. Absorptive permeability of AA-Su-Saq was elevated about 4-5 fold and efflux index reduced by about 13-15 fold across the polarized MDCK-MDR1 and Caco-2 cells. Absorptive permeability of AA-Su-Saq decreased 44% in the presence of 5 mM AA across MDCK-MDR1 cells. AA-Su-Saq was devoid of cytotoxicity over the concentration range studied. AA-Su-Saq significantly enhanced the metabolic stability but lowered the affinity towards CYP3A4. In conclusion, prodrug modification of Saq through conjugation to AA via a linker significantly raised the absorptive permeability and metabolic stability. Such modification also caused significant evading of P-gp mediated efflux and CYP3A4 mediated metabolism. SVCT targeted prodrug approach can be an attractive strategy to enhance the oral absorption and systemic bioavailability of anti-HIV protease inhibitors. PMID:21571053
NASA Astrophysics Data System (ADS)
Lisabeth, Harrison Paul
Interaction of rocks with fluids can significantly change mineral assemblage and structure. This so-called hydrothermal alteration is ubiquitous in the Earth's crust. Though the behavior of hydrothermally altered rocks can have planet-scale consequences, such as facilitating oceanic spreading along slow ridge segments and recycling volatiles into the mantle at subduction zones, the mechanisms involved in the hydrothermal alteration are often microscopic. Fluid-rock interactions take place where the fluid and rock meet. Fluid distribution, flux rate and reactive surface area control the efficiency and extent of hydrothermal alteration. Fluid-rock interactions, such as dissolution, precipitation and fluid mediated fracture and frictional sliding lead to changes in porosity and pore structure that feed back into the hydraulic and mechanical behavior of the bulk rock. Examining the nature of this highly coupled system involves coordinating observations of the mineralogy and structure of naturally altered rocks and laboratory investigation of the fine scale mechanisms of transformation under controlled conditions. In this study, I focus on fluid-rock interactions involving two common lithologies, carbonates and ultramafics, in order to elucidate the coupling between mechanical, hydraulic and chemical processes in these rocks. I perform constant strain-rate triaxial deformation and constant-stress creep tests on several suites of samples while monitoring the evolution of sample strain, permeability and physical properties. Subsequent microstructures are analyzed using optical and scanning electron microscopy. This work yields laboratory-based constraints on the extent and mechanisms of water weakening in carbonates and carbonation reactions in ultramafic rocks. I find that inundation with pore fluid thereby reducing permeability. This effect is sensitive to pore fluid saturation with respect to calcium carbonate. Fluid inundation weakens dunites as well. The addition of carbon dioxide to pore fluid enhances compaction and partial recovery of strength compared to pure water samples. Enhanced compaction in CO2-rich fluid samples is not accompanied by enhanced permeability reduction. Analysis of sample microstructures indicates that precipitation of carbonates along fracture surfaces is responsible for the partial restrengthening and channelized dissolution of olivine is responsible for permeability maintenance.
NASA Astrophysics Data System (ADS)
Senger, Kim; Buckley, Simon J.; Chevallier, Luc; Fagereng, Åke; Galland, Olivier; Kurz, Tobias H.; Ogata, Kei; Planke, Sverre; Tveranger, Jan
2015-02-01
Igneous intrusions act as both carriers and barriers to subsurface fluid flow and are therefore expected to significantly influence the distribution and migration of groundwater and hydrocarbons in volcanic basins. Given the low matrix permeability of igneous rocks, the effective permeability in- and around intrusions is intimately linked to the characteristics of their associated fracture networks. Natural fracturing is caused by numerous processes including magma cooling, thermal contraction, magma emplacement and mechanical disturbance of the host rock. Fracturing may be locally enhanced along intrusion-host rock interfaces, at dyke-sill junctions, or at the base of curving sills, thereby potentially enhancing permeability associated with these features. In order to improve our understanding of fractures associated with intrusive bodies emplaced in sedimentary host rocks, we have investigated a series of outcrops from the Karoo Basin of the Eastern Cape province of South Africa, where the siliciclastic Burgersdorp Formation has been intruded by various intrusions (thin dykes, mid-sized sheet intrusions and thick sills) belonging to the Karoo dolerite. We present a quantified analysis of fracturing in- and around these igneous intrusions based on five outcrops at three individual study sites, utilizing a combination of field data, high-resolution lidar virtual outcrop models and image processing. Our results show a significant difference between the three sites in terms of fracture orientation. The observed differences can be attributed to contrasting intrusion geometries, outcrop geometry (for lidar data) and tectonic setting. Two main fracture sets were identified in the dolerite at two of the sites, oriented parallel and perpendicular to the contact respectively. Fracture spacing was consistent between the three sites, and exhibits a higher degree of variation in the dolerites compared to the host rock. At one of the study sites, fracture frequency in the surrounding host rock increases slightly toward the intrusion at approximately 3 m from the contact. We conclude by presenting a conceptual fluid flow model, showing permeability enhancement and a high potential for fluid flow-channeling along the intrusion-host rock interfaces.
Luo, Shuanghui; Wang, Zhiying; Patel, Mitesh; Khurana, Varun; Zhu, Xiaodong; Pal, Dhananjay; Mitra, Ashim K
2011-07-29
In order to improve oral absorption, a novel prodrug of saquinavir (Saq), ascorbyl-succinic-saquinavir (AA-Su-Saq) targeting sodium dependent vitamin C transporter (SVCT) was synthesized and evaluated. Aqueous solubility, stability and cytotoxicity were determined. Affinity of AA-Su-Saq towards efflux pump P-glycoprotein (P-gp) and recognition of AA-Su-Saq by SVCT were studied. Transepithelial permeability across polarized MDCK-MDR1 and Caco-2 cells were determined. Metabolic stability of AA-Su-Saq in rat liver microsomes was investigated. AA-Su-Saq appears to be fairly stable in both DPBS and Caco-2 cells with half lives of 9.65 and 5.73 h, respectively. Uptake of [(3)H]Saquinavir accelerated by 2.7 and 1.9 fold in the presence of 50 μM Saq and AA-Su-Saq in MDCK-MDR1 cells. Cellular accumulation of [(14)C]AA diminished by about 50-70% relative to control in the presence of 200 μM AA-Su-Saq in MDCK-MDR1 and Caco-2 cells. Uptake of AA-Su-Saq was lowered by 27% and 34% in the presence of 5mM AA in MDCK-MDR1 and Caco-2 cells, respectively. Absorptive permeability of AA-Su-Saq was elevated about 4-5 fold and efflux index reduced by about 13-15 fold across the polarized MDCK-MDR1 and Caco-2 cells. Absorptive permeability of AA-Su-Saq decreased 44% in the presence of 5mM AA across MDCK-MDR1 cells. AA-Su-Saq was devoid of cytotoxicity over the concentration range studied. AA-Su-Saq significantly enhanced the metabolic stability but lowered the affinity towards CYP3A4. In conclusion, prodrug modification of Saq through conjugation to AA via a linker significantly raised the absorptive permeability and metabolic stability. Such modification also caused significant evading of P-gp mediated efflux and CYP3A4 mediated metabolism. SVCT targeted prodrug approach can be an attractive strategy to enhance the oral absorption and systemic bioavailability of anti-HIV protease inhibitors. Copyright © 2011 Elsevier B.V. All rights reserved.
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.
Maserati, Lorenzo; Meckler, Stephen M.; Bachman, Jonathan E.; ...
2017-10-18
Despite the availability of chemistries to tailor the pore architectures of microporous polymer membranes for chemical separations, trade-offs in permeability and selectivity with functional group manipulations nevertheless persist, which ultimately places an upper bound on membrane performance. We introduce a new design strategy to uncouple these attributes of the membrane. Key to our success is the incorporation of phase-change metal-organic frameworks (MOFs) into the polymer matrix, which can be used to increase the solubility of a specific gas in the membrane, and thereby its permeability. We further show that it is necessary to scale the size of the phase-change MOFmore » to nanoscopic dimensions, in order to take advantage of this effect in a gas separation. Our observation of an increase in solubility and permeability of only one of the gases during steady-state permeability measurements suggests fast exchange between free and chemisorbed gas molecules within the MOF pores. While the kinetics of this exchange in phase-change MOFs are not yet fully understood, their role in enhancing the efficacy and efficiency of the separation is clearly a compelling new direction for membrane technology.« less
Effects of roughness and permeability on solute transfer at the sediment water interface.
Han, Xu; Fang, Hongwei; He, Guojian; Reible, Danny
2018-02-01
Understanding the mechanisms of solute transfer across the sediment-water interface plays a crucial role in water quality prediction and management. In this study, different arranged particles are used to form typical rough and permeable beds. Large Eddy Simulation (LES) is used to model the solute transfer from the overlying water to sediment beds. Three rough wall turbulence regimes, i.e., smooth, transitional and rough regime, are separately considered and the effects of bed roughness on solute transfer are quantitatively analyzed. Results show that the classic laws related to Schmidt numbers can well reflect the solute transfer under the smooth regime with small roughness Reynolds numbers. Under the transitional regime, the solute transfer coefficient (K L + ) is enhanced and the effect of Schmidt number is weakened by increasing roughness Reynolds number. Under the rough regime, the solute transfer is suppressed by the transition layer (Brinkman layer) and controlled by the bed permeability. Moreover, it is found that water depth, friction velocity and bed permeability can be used to estimate the solute transfer velocity (K L ) under the completely rough regime. Copyright © 2017 Elsevier Ltd. All rights reserved.
Transport of surface engineered polyamidoamine (PAMAM) dendrimers across IPEC-J2 cell monolayers.
Pisal, Dipak S; Yellepeddi, Venkata K; Kumar, Ajay; Palakurthi, Srinath
2008-11-01
The aim of our study was to prepare arginine-and ornithine-conjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM(G4) dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P(app)) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechanisms are in progress, results of the present study suggest the potential of dendrimer-polyamine conjugates as the carriers for antigen/drug delivery through the oral mucosa.
Pore-scale lattice Boltzmann simulation of micro-gaseous flow considering surface diffusion effect
Wang, Junjian; Kang, Qinjun; Chen, Li; ...
2016-11-21
Some recent studies have shown that adsorbed gas and its surface diffusion have profound influence on micro-gaseous flow through organic pores in shale gas reservoirs. Here, a multiple-relaxation-time (MRT) LB model is adopted to estimate the apparent permeability of organic shale and a new boundary condition, which combines Langmuir adsorption theory with Maxwellian diffusive reflection boundary condition, is proposed to capture gas slip and surface diffusion of adsorbed gas. The simulation results match well with previous studies carried out using Molecular Dynamics (MD) and show that Maxwell slip boundary condition fails to characterize gas transport in the near wall regionmore » under the influence of the adsorbed gas. The total molar flux can be either enhanced or reduced depending on variations in adsorbed gas coverage and surface diffusion velocity. The effects of pore width, pressure as well as Langmuir properties on apparent permeability of methane transport in organic pores are further studied. It is found that the surface transport plays a significant role in determining the apparent permeability, and the variation of apparent permeability with pore size and pressure is affected by the adsorption and surface diffusion.« less
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
Pham-The, Hai; Casañola-Martin, Gerardo; Garrigues, Teresa; Bermejo, Marival; González-Álvarez, Isabel; Nguyen-Hai, Nam; Cabrera-Pérez, Miguel Ángel; Le-Thi-Thu, Huong
2016-02-01
In many absorption, distribution, metabolism, and excretion (ADME) modeling problems, imbalanced data could negatively affect classification performance of machine learning algorithms. Solutions for handling imbalanced dataset have been proposed, but their application for ADME modeling tasks is underexplored. In this paper, various strategies including cost-sensitive learning and resampling methods were studied to tackle the moderate imbalance problem of a large Caco-2 cell permeability database. Simple physicochemical molecular descriptors were utilized for data modeling. Support vector machine classifiers were constructed and compared using multiple comparison tests. Results showed that the models developed on the basis of resampling strategies displayed better performance than the cost-sensitive classification models, especially in the case of oversampling data where misclassification rates for minority class have values of 0.11 and 0.14 for training and test set, respectively. A consensus model with enhanced applicability domain was subsequently constructed and showed improved performance. This model was used to predict a set of randomly selected high-permeability reference drugs according to the biopharmaceutics classification system. Overall, this study provides a comparison of numerous rebalancing strategies and displays the effectiveness of oversampling methods to deal with imbalanced permeability data problems.
Apparatus and process for water treatment
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.
Outstanding issues for new geothermal resource assessments
Williams, C.F.; Reed, M.J.
2005-01-01
A critical question for the future energy policy of the United States is the extent to which geothermal resources can contribute to an ever-increasing demand for electricity. Electric power production from geothermal sources exceeds that from wind and solar combined, yet the installed capacity falls far short of the geothermal resource base characterized in past assessments, even though the estimated size of the resource in six assessments completed in the past 35 years varies by thousands of Megawatts-electrical (MWe). The U. S. Geological Survey (USGS) is working closely with the Department of Energy's (DOE) Geothermal Research Program and other geothermal organizations on a three-year effort to produce an updated assessment of available geothermal resources. The new assessment will introduce significant changes in the models for geothermal energy recovery factors, estimates of reservoir permeability, limits to temperatures and depths for electric power production, and include the potential impact of evolving Enhanced (or Engineered) Geothermal Systems (EGS) technology.
Peng, Shoujian; Fang, Zhiming; Shen, Jian; Xu, Jiang; Wang, Geoff
2017-10-30
The cleat compressibility of coal is a key parameter that is extensively used in modeling the coal reservoir permeability for Coal Bed Methane (CBM) recovery. Cleat compressibility is often determined from the permeability measurement made at different confining pressures but with a constant pore pressure. Hence, this parameter ignores the sorption strain effects on the cleat compressibility. By using the transient pulse decay (TPD) technique, this study presents the results from a laboratory characterization program using coal core drilled from different bedding directions to estimate gas permeability and coal cleat compressibility under different pore pressures while maintaining effective stress constant. Cleat compressibility was determined from permeability and sorption strain measurements that are made at different pore pressures under an effective stress constant. Results show that the cleat compressibility of coal increases slightly with the increase of pore pressure. Moreover, the cleat compressibility of Sample P (representing the face cleats in coal) is larger than that of Sample C (representing the butt cleats in coal). This result suggests that cleat compressibility should not be regarded as constant in the modeling of the CBM recovery. Furthermore, the compressibility of face cleats is considerably sensitive to the sorption-induced swelling/shrinkage and offers significant effects on the coal permeability.
Ratnoff, Oscar D.; Pensky, Jack; Ogston, Derek; Naff, George B.
1969-01-01
The fraction of human serum designated as C'1 esterase inhibitor is known to inhibit the action of C'1 esterase, a plasma kallikrein, and PF/Dil, an enzyme in plasma enhancing cutaneous vascular permeability. In the present study, C'1 esterase inhibitor has been found to block the actions of plasmin and the C'1r subcomponent of the first component of complement, and to retard the generation of PF/Dil. No inhibition of blood clotting or of the generation of plasmin was demonstrable. PMID:4178758
NASA Astrophysics Data System (ADS)
Sahu, Bhanu P.; Das, Malay K.
2014-04-01
Furosemide is a poorly soluble diuretic used for treatment of hypertension and edema. It has very poor or variable oral bioavailability due to its reduced solubility in gastric fluid and reduced permeability in intestinal fluid. The aim of this study was to prepare nanosuspension of furosemide to enhance its oral bioavailability by increasing its dissolution in stomach where it has better permeability. Full factorial design was used for a systematic approach of formulation and optimization. The nanosuspensions were prepared by precipitation with ultrasonication method. Polyvinyl acetate was used for sterically stabilizing the nanosuspensions. The diffusing drug concentration and stabilizer were used as the factors and the particle size, polydispersity index, and drug release were selected as dependent variables and characterized. The effect of nanoprecipitation on enhancement of oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption studies in rats and compared to pure drug. Quality by design using full factorial design provided a systematic approach in optimizing nanosuspensions to produce products with desired quality. Stable nanosuspension were obtained with average size range of the precipitated nanoparticles between 150 and 300 nm and were found to be homogenous showing a narrow polydispersity index of 0.3 ± 0.1. The in vivo studies on rats revealed a significant increase in the oral absorbtion of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and C max values of nanosuspension were approximately 1.38- and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06 ± 0.02 % decrease in systolic blood pressure compared to 13.37 + 0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamic effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.
Lee, GeonHui; Jun, Yesl; Jang, HeeYeong; Yoon, Junghyo; Lee, JaeSeo; Hong, MinHyung; Chung, Seok; Kim, Dong-Hwee; Lee, SangHoon
2018-01-01
Oxygen availability is a critical factor in regulating cell viability that ultimately contributes to the normal morphogenesis and functionality of human tissues. Among various cell culture platforms, construction of 3D multicellular spheroids based on microwell arrays has been extensively applied to reconstitute in vitro human tissue models due to its precise control of tissue culture conditions as well as simple fabrication processes. However, an adequate supply of oxygen into the spheroidal cellular aggregation still remains one of the main challenges to producing healthy in vitro spheroidal tissue models. Here, we present a novel design for controlling the oxygen distribution in concave microwell arrays. We show that oxygen permeability into the microwell is tightly regulated by varying the poly-dimethylsiloxane (PDMS) bottom thickness of the concave microwells. Moreover, we validate the enhanced performance of the engineered microwell arrays by culturing non-proliferated primary rat pancreatic islet spheroids on varying bottom thickness from 10 μm to 1050 μm. Morphological and functional analyses performed on the pancreatic islet spheroids grown for 14 days prove the long-term stability, enhanced viability, and increased hormone secretion under the sufficient oxygen delivery conditions. We expect our results could provide knowledge on oxygen distribution in 3-dimensional spheroidal cell structures and critical design concept for tissue engineering applications. In this study, we present a noble design to control the oxygen distribution in concave microwell arrays for the formation of highly functional pancreatic islet spheroids by engineering the bottom of the microwells. Our new platform significantly enhanced oxygen permeability that turned out to improve cell viability and spheroidal functionality compared to the conventional thick-bottomed 3-D culture system. Therefore, we believe that this could be a promising medical biotechnology platform to further develop high-throughput tissue screening system as well as in vivo-mimicking customised 3-D tissue culture systems. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Consolino, Lorena; Longo, Dario Livio; Sciortino, Marianna; Dastrù, Walter; Cabodi, Sara; Giovenzana, Giovanni Battista; Aime, Silvio
2017-07-01
Most metastatic gastrointestinal stromal tumors (GISTs) develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging (MRI) functional approach. Immunodeficient mice (n = 8 for each cell line) were grafted with imatinib-sensitive (GIST882 and GIST-T1) and imatinib-resistant (GIST430) human cell lines. Dynamic contrast-enhanced MRI (DCE-MRI) was performed on GIST xenografts to quantify tumor vessel permeability (K trans ) and vascular volume fraction (v p ). Microvessel density (MVD), permeability (mean dextran density, MDD), and angiogenic markers were evaluated by immunofluorescence and western blot assays. Dynamic contrast-enhanced magnetic resonance imaging showed significantly increased vessel density (P < 0.0001) and permeability (P = 0.0002) in imatinib-resistant tumors compared to imatinib-sensitive ones. Strong positive correlations were observed between MRI estimates, K trans and v p , and their related ex vivo values, MVD (r = 0.78 for K trans and r = 0.82 for v p ) and MDD (r = 0.77 for K trans and r = 0.94 for v p ). In addition, higher expression of vascular endothelial growth factor receptors (VEGFR2 and VEFGR3) was seen in GIST430. Dynamic contrast-enhanced magnetic resonance imaging highlighted marked differences in tumor vasculature and microenvironment properties between imatinib-resistant and imatinib-sensitive GISTs, as also confirmed by ex vivo assays. These results provide new insights into the role that DCE-MRI could play in GIST characterization and response to GIST treatment. Validation studies are needed to confirm these findings.
NASA Astrophysics Data System (ADS)
Varshney, G. K.; Kintali, S. R.; Gupta, P. K.; Das, K.
2017-02-01
We report the use of interface selective Second Harmonic generation technique to investigate the transport of the LDS cation across POPG liposomes in the pH range of 4.0 to 8.0 in the presence and absence of two amphiphilic drugs, Curcumin and Chlorin-p6 (Cp6). Our results show that bilayer permeability of liposomes is significantly affected by the presence of the drugs and pH of the medium as evidenced by significant changes in the transport kinetics of the LDS. Studies carried out in the pH range 4.0-8.0 show that while Cp6 significantly enhanced the transport of LDS at pH 4.0, the transport of the cation was seen to increase with increasing pH, with maximum effect at pH 7.4 for Curcumin. The pH dependent bilayer localization of both the drugs was investigated by conducting steady state FRET studies using DPH labeled lipids as donors. The FRET results and the relative population of the various ionic/nonionic species of the drugs at different pH suggest that distance dependent interaction between the various ionic species of the drugs and polar head groups of the lipid is responsible for the observed pH dependence enhancement of the drug induced membrane permeability. Another interesting observation was that the stability of Curcumin in presence of POPG liposomes was observed to degrade significantly near physiological pH (7.4 and 8.0). Although this degradation did not affect the liposome integrity, interestingly this was observed to enhance the transport of the LDS cation across the bilayer. That the degradation products of Curcumin are equally effective as the drug itself in enhancing the membrane permeability lends additional support to the current opinion that the bioactive degradation products of the drug may have a significant contribution to its observed pharmacological effects.
Pervious pavements - installation, operations and strength part 3 : permeable paver systems.
DOT National Transportation Integrated Search
2011-08-01
Pervious pavement systems are now being recognized as a best management practice by the Environmental Protection Agency and the state of Florida. The pervious pavement systems are designed to have enhanced pore sizes in the surface layer compared to ...
Causes and effects of poor drainage in cranberry farms
USDA-ARS?s Scientific Manuscript database
Soils that support the growth of cranberries often cap geologic deposits of organic sediment, such as peat. However, low-permeability organic sediments may result in inadequate drainage that diminishes plant productivity and enhances fruit rot. Consequently, new constructions of cranberry farms are ...
Enhanced graphene oxide membranes and methods for making same
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shin, Yongsoon; Gotthold, David W.; Fifield, Leonard S.
A method for making a graphene oxide membrane and a resulting free-standing graphene oxide membrane that provides desired qualities of water permeability and selectivity at larger sizes, thinner cross sections, and with increased ruggedness as compared to existing membranes and processes.
SITE TECHNOLOGY CAPSULE: KAI RADIO FREQUENCY HEATING TECHNOLOGY
KAI developed a patented, in situ RFH technology to enhance the removal of volatile and semi-volatile organics by soil vapor extraction (SVE). Electromagnetic energy heats the soil resulting in increased contaminant vapor pressures and soil permeability that may increase with dry...
Diffusion in Clay Layers and Groundwater Remediation
In a collaborative SERDP-funded study, researchers from the Air Force Institute of Technology, the U.S. Environmental Protection Agency, and the University of Michigan developed a numerical model that simulates the enhanced transport of CAHs into and out of low permeability clay ...
Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P
2002-10-24
The aim of the present study was to develop a membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 4%w/w of limonene as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate (VA) content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA membrane 2825 (28% w/w VA) or membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE 4A MED/skin composite was higher than that coated with MA-31or MA-38. Thus a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED and 2%w/w HPC gel as reservoir containing 4%w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady state plasma concentration of the drug with minimal fluctuations for 20 h with improved bioavailability in comparison with the immediate release capsule dosage form. Copyright 2002 Elsevier Science B.V.
Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P
2003-05-01
A membrane-moderated transdermal therapeutic system of nicardipine hydrochloride was developed using 2% w/w hydroxypropylcellulose (HPC) gel as a reservoir system containing 5% w/w of menthol as a penetration enhancer. The permeability flux of nicardipine hydrochloride through the ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28% w/w vinyl acetate) or EVA 2825 membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new transdermal therapeutic system for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED, and 2% w/w HPC gel as reservoir containing 5% w/w of menthol as a penetration enhancer. In vivo studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 26h with improved bioavailability in comparison with the immediate release capsule dosage form.
Mei, Kuo-Ching; Bai, Jie; Lorrio, Silvia; Wang, Julie Tzu-Wen; Al-Jamal, Khuloud T
2016-11-01
Nanocarriers take advantages of the enhanced permeability and retention (EPR) to accumulate passively in solid tumors. Magnetic targeting has shown to further enhance tumor accumulation in response to a magnetic field gradient. It is widely known that passive accumulation of nanocarriers varies hugely in tumor tissues of different tumor vascularization. It is hypothesized that magnetic targeting is likely to be influenced by such factors. In this work, magnetic targeting is assessed in a range of subcutaneously implanted murine tumors, namely, colon (CT26), breast (4T1), lung (Lewis lung carcinoma) cancer and melanoma (B16F10). Passively- and magnetically-driven tumor accumulation of the radiolabeled polymeric magnetic nanocapsules are assessed with gamma counting. The influence of tumor vasculature, namely, the tumor microvessel density, permeability and diameter on passive and magnetic tumor targeting is assessed with the aid of the retrospective design of experiment (DoE) approach. It is clear that the three tumor vascular parameters contribute greatly to both passive and magnetically targeted tumor accumulation but play different roles when nanocarriers are targeted to the tumor with different strategies. It is concluded that tumor permeability is a rate-limiting factor in both targeting modes. Diameter and microvessel density influence passive and magnetic tumor targeting, respectively. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Magnetic resonance dispersion imaging for localization of angiogenesis and cancer growth.
Mischi, Massimo; Turco, Simona; Lavini, Cristina; Kompatsiari, Kyveli; de la Rosette, Jean J M C H; Breeuwer, Marcel; Wijkstra, Hessel
2014-08-01
Cancer angiogenesis can be imaged by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Pharmacokinetic modeling can be used to assess vascular perfusion and permeability, but the assessment of angiogenic changes in the microvascular architecture remains challenging. This article presents 2 models enabling the characterization of the microvascular architecture by DCE-MRI. The microvascular architecture is reflected in the dispersion coefficient according to the convective dispersion equation. A solution of this equation, combined with the Tofts model, permits defining a dispersion model for magnetic resonance imaging. A reduced dispersion model is also presented. The proposed models were evaluated for prostate cancer diagnosis. Dynamic contrast-enhanced magnetic resonance imaging was performed, and concentration-time curves were calculated in each voxel. The simultaneous generation of parametric maps related to permeability and dispersion was obtained through model fitting. A preliminary validation was carried out through comparison with the histology in 15 patients referred for radical prostatectomy. Cancer localization was accurate with both dispersion models, with an area under the receiver operating characteristic curve greater than 0.8. None of the compared parameters, aimed at assessing vascular permeability and perfusion, showed better results. A new DCE-MRI method is proposed to characterize the microvascular architecture through the assessment of intravascular dispersion, without the need for separate arterial-input-function estimation. The results are promising and encourage further research.
Mathison, R; Davison, J S
1994-05-02
The effects of intravenous injection of prostaglandin E2 (PGE2), substance P (SP) and a metabolically stable SP analogue, [pGlu5,Me-Phe8,Sar9]-SP (5-11) on plasma extravasation of albumin in the rat after blockade of prostaglandin synthesis with indomethacin or chemical sympathectomy with guanethidine were studied. Blood pressure was decreased by all agonists, but only the hypotensive effects of SP were enhanced by pretreatment with indomethacin and guanethidine. The increase in plasma extravasation induced by PGE2 in the tongue, skin and lungs was blocked by both guanethidine and indomethacin. Pretreatment of the rats with guanethidine or indomethacin increased extravasation induced by SP in the tongue-tip, dorsal skin and foot, but decreased the enhanced permeability in the pinna, and did not alter the actions of the peptide in other tissues. In contrast, both guanethidine and indomethacin pretreatment increased vascular permeability responses to [pGlu5,Me-Phe8,Sar9]-SP (5-11) administration in 9 and 14 of 16 tissues examined, respectively. Thus, intact sympathetic nerves and functional cycloxygenase activity exert inhibitory constraints on the vascular permeability effects of intravenously administered SP or its analogue. On the other hand the integrity of the sympathetic nerves and prostaglandin synthesis are required for PGE2-induced increases in vascular leak.
Ibraimi, Filiz; Kriz, Dario; Lu, Min; Hansson, Lars-Olof; Kriz, Kirstin
2006-02-01
A rapid (5.5 min) one-step whole blood C-reactive protein (CRP) magnetic permeability immunoassay utilizing monoclonal antibody conjugated dextran iron oxide nanoparticles (70 nm) as superparamagnetic labels and mixed fractions (1:1 ratio of 15-40 and 60 microm) of polyclonal anti-CRP conjugated silica microparticles for enhanced sedimentation is described. In this one-step assay procedure, a whole blood sample (4 microl) is applied to an assay glass vial, containing both antibody conjugates, and mixed for 30 s. The target analyte, CRP, forms a sandwich complex between the conjugated nanoparticles and microparticles, and, subsequently, the complex sediments under normal gravitation within 5 min to the bottom of the vial. The magnetic permeability increase of the sediment due to the presence of the complexed superparamagnetic nanoparticles is determined using an inductance-based transducer. Assayed patient whole blood samples were compared with the Abbott Diagnostics Architect reference method. A strong linear correlation was observed for the CRP concentration range 0-260 mg/l in whole blood (y=1.001x+0.42, R2=0.982, n=50). The CRP assay presented showed a limit of detection of 3 mg/l and a total imprecision (coefficient of variation) of 10.5%. On the basis of our observations, we propose a rapid, one-step, CRP assay for near-patient testing.
Quispe Calla, N E; Vicetti Miguel, R D; Boyaka, P N; Hall-Stoodley, L; Kaur, B; Trout, W; Pavelko, S D; Cherpes, T L
2016-11-01
Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection.
Yamaki, Tsutomu; Kamiya, Yusuke; Ohtake, Kazuo; Uchida, Masaki; Seki, Toshinobu; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi
2014-09-01
Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we investigated the mechanism of disappearance of TJ proteins from cell-cell junctions after the application of PLA to Caco-2 cell monolayers. The membrane conductance (Gt), FITC-dextran (FD-4) permeability, and localization of TJ proteins were examined after the treatment of Caco-2 cell monolayers with PLA in the presence of various endocytosis inhibitors. In addition, the localization of endosome marker proteins was also observed. Clathrin-mediated endocytosis inhibitors suppressed the increase in Gt and Papp of FD-4 induced by PLA, and also significantly suppressed the disappearance of TJ proteins induced by PLA. Furthermore, occludin, one of the TJ proteins, colocalized with early endosome and recycling endosomes after the internalization of occludin induced by PLA, and then was recycled to the cell-cell junctions. PLA induced the transient internalization of TJ proteins in cell-cell junctions via clathrin-mediated endocytosis, subsequently increasing the permeability of the Caco-2 cell monolayer to FD-4 via a paracellular route.
Barnes, Samuel R; Ng, Thomas S C; Montagne, Axel; Law, Meng; Zlokovic, Berislav V; Jacobs, Russell E
2016-05-01
To determine optimal parameters for acquisition and processing of dynamic contrast-enhanced MRI (DCE-MRI) to detect small changes in near normal low blood-brain barrier (BBB) permeability. Using a contrast-to-noise ratio metric (K-CNR) for Ktrans precision and accuracy, the effects of kinetic model selection, scan duration, temporal resolution, signal drift, and length of baseline on the estimation of low permeability values was evaluated with simulations. The Patlak model was shown to give the highest K-CNR at low Ktrans . The Ktrans transition point, above which other models yielded superior results, was highly dependent on scan duration and tissue extravascular extracellular volume fraction (ve ). The highest K-CNR for low Ktrans was obtained when Patlak model analysis was combined with long scan times (10-30 min), modest temporal resolution (<60 s/image), and long baseline scans (1-4 min). Signal drift as low as 3% was shown to affect the accuracy of Ktrans estimation with Patlak analysis. DCE acquisition and modeling parameters are interdependent and should be optimized together for the tissue being imaged. Appropriately optimized protocols can detect even the subtlest changes in BBB integrity and may be used to probe the earliest changes in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis. © 2015 Wiley Periodicals, Inc.
Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim
2012-11-01
In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.
Soft contact lens biomaterials from bioinspired phospholipid polymers.
Goda, Tatsuro; Ishihara, Kazuhiko
2006-03-01
Soft contact lens (SCL) biomaterials originated from the discovery of a poly(2-hydroxyethyl methacrylate) (poly[HEMA])-based hydrogel in 1960. Incorporation of hydrophilic polymers into poly(HEMA) hydrogels was performed in the 1970-1980s, which brought an increase in the equilibrium water content, leading to an enhancement of the oxygen permeability. Nowadays, the poly(HEMA)-based hydrogels have been applied in disposable SCL. At the same time, high oxygen-permeable silicone hydrogels were produced, which made it possible to continually wear SCL. Recently, numerous trials for improving the water wettability of silicone hydrogels have been performed. However, little attention has been paid to improving their anti-biofouling properties and biocompatibility. Since biomimetic phospholipid polymers possess excellent anti-biofouling properties and biocompatibility they have the potential to play a valuable role in the surface modification of the silicone hydrogel. The representative phospholipid polymers containing a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit suppressed nonspecific protein adsorption, increased cell compatibility and contributed to blood compatible biomaterials. The MPC polymer coating on the silicone hydrogel improved its water wettability and biocompatibility, while maintaining high oxygen permeability compared with the original silicone hydrogel. Furthermore, the newly prepared phospholipid-type intermolecular crosslinker made it possible to synthesize a 100% phospholipid polymer hydrogel that can enhance the anti-biofouling properties and biocompatibility. In this review, the authors discuss how polymer hydrogels should be designed in order to obtain a biocompatible SCL and future perspectives.
NASA Astrophysics Data System (ADS)
Li, Siwei; Li, Jun; Liu, Zhuochu; Wang, Min; Yue, Liang
2017-05-01
After the access of household distributed photovoltaic, conditions of high permeability generally occur, which cut off the connection between distributed power supply and major network rapidly and use energy storage device to realize electrical energy storage. The above operations cannot be adequate for the power grid health after distributed power supply access any more from the perspective of economy and rationality. This paper uses the integration between device and device, integration between device and system and integration between system and system of household microgrid and household energy efficiency management, to design household microgrid building program and operation strategy containing household energy efficiency management, to achieve efficient integration of household energy efficiency management and household microgrid, to effectively solve problems of high permeability of household distributed power supply and so on.
Nanoparticle Delivery Enhancement With Acoustically Activated Microbubbles
Mullin, Lee B; Phillips, Linsey C; Dayton, Paul A
2013-01-01
The application of microbubbles and ultrasound to deliver nanoparticle carriers for drug and gene delivery is an area that has expanded greatly in recent years. Under ultrasound exposure, microbubbles can enhance nanoparticle delivery by increasing cellular and vascular permeability. In this review, the underlying mechanisms of enhanced nanoparticle delivery with ultrasound and microbubbles and various proposed delivery techniques are discussed. Additionally, types of nanoparticles currently being investigated in preclinical studies, as well as the general limitations and benefits of a microbubble-based approach to nanoparticle delivery are reviewed. PMID:23287914
Petit, P X; Goubern, M; Diolez, P; Susin, S A; Zamzami, N; Kroemer, G
1998-04-10
Upon induction of permeability transition with different agents (Ca2+, tert-butyl hydroperoxide, atractyloside), mouse hepatocyte mitochondria manifest a disruption of outer membrane integrity leading to the release of cytochrome c and apoptosis-inducing factor (AIF), two proteins which are involved in programmed cell death (apoptosis). Chelation of Ca2+ shortly (within 2 min) after its addition to isolated mitochondria reestablished the mitochondrial transmembrane potential (deltapsi(m)), prevented induction of large amplitude swelling and release of both cytochrome c and AIF. In contrast, late Ca2+ chelation (10 min after addition of Ca2+) failed to affect these parameters. Cytochrome c appears to be released through a mechanically damaged outer mitochondrial membrane rather than via a specific release mechanism. These findings clarify the mechanisms through which irreversible permeability transition occurs with subsequent large amplitude swelling culminating in the release of intermembrane proteins from mitochondria. Moreover, they confirm the hypothesis formulated by Skulachev [FEBS Lett. 397 (1996) 7-10 and Q. Rev. Biophys. 29 (1996) 169-2021 linking permeability transition to activation of the apoptogenic catabolic enzymes.
TORO II simulations of induction heating in ferromagnetic materials
DOE Office of Scientific and Technical Information (OSTI.GOV)
Adkins, D.R.; Gartling, D.K.; Kelley, J.B.
TORO II is a finite element computer program that is used in the simulation of electric and magnetic fields. This code, which was developed at Sandia National Laboratories, has been coupled with a finite element thermal code, COYOTE II, to predict temperature profiles in inductively heated parts. The development of an effective technique to account for the nonlinear behavior of the magnetic permeability in ferromagnetic parts is one of the more difficult aspects of solving induction heating problems. In the TORO II code, nonlinear, spatially varying magnetic permeability is approximated by an effective permeability on an element-by-element basis that effectivelymore » provides the same energy deposition that is produced when the true permeability is used. This approximation has been found to give an accurate estimate of the volumetric heating distribution in the part, and predicted temperature distributions have been experimentally verified using a medium carbon steel and a 10kW industrial induction heating unit. Work on the model was funded through a Cooperative Research and Development Agreement (CRADA) between the Department of Energy and General Motors` Delphi Saginaw Steering Systems.« less
NASA Astrophysics Data System (ADS)
Yoneda, J.; Oshima, M.; Kida, M.; Kato, A.; Konno, Y.; Jin, Y.; Waite, W. F.; Jang, J.; Kumar, P.; Tenma, N.
2017-12-01
Pressure coring and analysis technology allows for gas hydrate to be recovered from the deep seabed, transferred to the laboratory and characterized while continuously maintaining gas hydrate stability. For this study, dozens of hydrate-bearing pressure core sediment subsections recovered from the Krishna-Godavari Basin during India's National Gas Hydrate Program Expedition NGHP-02 were tested with Pressure Core Non-destructive Analysis Tools (PNATs) through a collaboration between Japan and India. PNATs, originally developed by AIST as a part of the Japanese National hydrate research program (MH21, funded by METI) conducted permeability, compression and consolidation tests under various effective stress conditions, including the in situ stress state estimated from downhole bulk density measurements. At the in situ effective stress, gas hydrate-bearing sediments had an effective permeability range of 0.01-10mD even at pore-space hydrate saturations above 60%. Permeability increased by 10 to 100 times after hydrate dissociation at the same effective stress, but these post-dissociation gains were erased when effective stress was increased from in situ values ( 1 MPa) to 10MPa in a simulation of the depressurization method for methane extraction from hydrate. Vertical-to-horizontal permeability anisotropy was also investigated. First-ever multi-stage loading tests and strain-rate alternation compression tests were successfully conducted for evaluating sediment strengthening dependence on the rate and magnitude of effective confining stress changes. In addition, oedometer tests were performed up to 40MPa of consolidation stress to simulate the depressurization method in ultra-deep sea environments. Consolidation curves measured with and without gas hydrate were investigated over a wide range of effective confining stresses. Compression curves for gas hydrate-bearing sediments were convex downward due to high hydrate saturations. Consolidation tests show that, regardless of the consolidation history with hydrate in place, the consolidation behavior after dissociation will first return to, then follow, the original normal consolidation curve for the hydrate-free host sediment.
Jeong, Sekyoo; Lee, Sin Hee; Park, Byeong Deog; Wu, Yan; Man, George; Man, Mao-Qiang
2016-03-01
The management of sensitive skin, which affects over 60% of the general population, has been a long-standing challenge for both patients and clinicians. Because defective epidermal permeability barrier is one of the clinical features of sensitive skin, barrier-enhancing products could be an optimal regimen for sensitive skin. In the present study, we evaluated the efficacy and safety of two barrier-enhancing products, i.e., Atopalm (®) Multi-Lamellar Emulsion (MLE) Cream and Physiogel (®) Intensive Cream for sensitive skin. 60 patients with sensitive skin, aged 22-40 years old, were randomly assigned to one group treated with Atopalm MLE Cream, and another group treated with Physiogel Intensive Cream twice daily for 4 weeks. Lactic acid stinging test scores (LASTS), stratum hydration (SC) and transepidermal water loss (TEWL) were assessed before, 2 and 4 weeks after the treatment. Atopalm MLE Cream significantly lowered TEWL after 2 and 4 weeks of treatment (p < 0.01). In contrast, Physiogel Intensive Cream significantly increased TEWL after 2 weeks of treatment (p < 0.05) while TEWL significantly decreased after 4-week treatments. Moreover, both Atopalm MLE Cream and Physiogel Intensive Cream significantly increased SC hydration, and improved LASTS after 4 weeks of treatment. Both barrier-enhancing products are effective and safe for improving epidermal functions, including permeability barrier, SC hydration and LASTS, in sensitive skin. These products could be a valuable alternative for management of sensitive skin. Veterans Affairs Medical Center, San Francisco, California, USA, and NeoPharm Co., Ltd., Daejeon, Korea.
Nanocomposites biodegradable coating on BOPET films to enhance hot seal strength properties
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barbaro, G., E-mail: giovannibarbaro@email.it; Galdi, M. R., E-mail: mrgaldi@unisa.it; Di Maio, L., E-mail: ldimaio@unisa.it
2015-12-17
The coating technology is a strategic solution to improve the properties of flexible packaging films. Indeed, additional functional layers are often designed and added as coating on the substrate, in order to improve the characteristic of the flexible packaging and to meet the requirements for the desired gas or vapour barrier, for adhesion and sealing, or for improving the film printability, its aesthetics and durability. Moreover, this technology allows to functionalize a polymeric substrate applying materials with different chemistry, rheology, thermal and structural characteristics. BOPET films are widely used for food packaging applications thanks to their good gas barrier andmore » mechanical properties, high transparency and for the excellent printability. In regard to sealing performance, BOPET films show poor sealing properties so they are mostly submitted to lamination processes with polyethylene. Nevertheless, this solution compromises the PET recyclability and influences the gas permeability of the multilayer PET based structures. The aim of this work is to investigate on the effect of nanocomposite biodegradable coatings for BOPET substrates in enhancing the heat sealing strength of eco-compatible PET/PLA films. At this regards, different percentages of Cloisite C30B (0%, 2% and 4%{sub wt/wt}) have been added to PLA by solution intercalation technique and the nanocomposite biodegradable materials produced have been applied on BOPET commercial films by casting. The BOPET coated films have been characterized in order to evaluate the heat sealing strength and the mechanical, gas permeability and surface properties. The results have shown that the addition of nanoclay in PLA coating significantly enhance the hot tack properties of the PET/PLA system produced, while the oxygen and water vapour permeability are slightly increased if compared to pure BOPET films.« less
Nanocomposites biodegradable coating on BOPET films to enhance hot seal strength properties
NASA Astrophysics Data System (ADS)
Barbaro, G.; Galdi, M. R.; Di Maio, L.; Incarnato, L.
2015-12-01
The coating technology is a strategic solution to improve the properties of flexible packaging films. Indeed, additional functional layers are often designed and added as coating on the substrate, in order to improve the characteristic of the flexible packaging and to meet the requirements for the desired gas or vapour barrier, for adhesion and sealing, or for improving the film printability, its aesthetics and durability. Moreover, this technology allows to functionalize a polymeric substrate applying materials with different chemistry, rheology, thermal and structural characteristics. BOPET films are widely used for food packaging applications thanks to their good gas barrier and mechanical properties, high transparency and for the excellent printability. In regard to sealing performance, BOPET films show poor sealing properties so they are mostly submitted to lamination processes with polyethylene. Nevertheless, this solution compromises the PET recyclability and influences the gas permeability of the multilayer PET based structures. The aim of this work is to investigate on the effect of nanocomposite biodegradable coatings for BOPET substrates in enhancing the heat sealing strength of eco-compatible PET/PLA films. At this regards, different percentages of Cloisite C30B (0%, 2% and 4%wt/wt) have been added to PLA by solution intercalation technique and the nanocomposite biodegradable materials produced have been applied on BOPET commercial films by casting. The BOPET coated films have been characterized in order to evaluate the heat sealing strength and the mechanical, gas permeability and surface properties. The results have shown that the addition of nanoclay in PLA coating significantly enhance the hot tack properties of the PET/PLA system produced, while the oxygen and water vapour permeability are slightly increased if compared to pure BOPET films.
Universal Linear Scaling of Permeability and Time for Heterogeneous Fracture Dissolution
NASA Astrophysics Data System (ADS)
Wang, L.; Cardenas, M. B.
2017-12-01
Fractures are dynamically changing over geological time scale due to mechanical deformation and chemical reactions. However, the latter mechanism remains poorly understood with respect to the expanding fracture, which leads to a positively coupled flow and reactive transport processes, i.e., as a fracture expands, so does its permeability (k) and thus flow and reactive transport processes. To unravel this coupling, we consider a self-enhancing process that leads to fracture expansion caused by acidic fluid, i.e., CO2-saturated brine dissolving calcite fracture. We rigorously derive a theory, for the first time, showing that fracture permeability increases linearly with time [Wang and Cardenas, 2017]. To validate this theory, we resort to the direct simulation that solves the Navier-Stokes and Advection-Diffusion equations with a moving mesh according to the dynamic dissolution process in two-dimensional (2D) fractures. We find that k slowly increases first until the dissolution front breakthrough the outbound when we observe a rapid k increase, i.e., the linear time-dependence of k occurs. The theory agrees well with numerical observations across a broad range of Peclet and Damkohler numbers through homogeneous and heterogeneous 2D fractures. Moreover, the theory of linear scaling relationship between k and time matches well with experimental observations of three-dimensional (3D) fractures' dissolution. To further attest to our theory's universality for 3D heterogeneous fractures across a broad range of roughness and correlation length of aperture field, we develop a depth-averaged model that simulates the process-based reactive transport. The simulation results show that, regardless of a wide variety of dissolution patterns such as the presence of dissolution fingers and preferential dissolution paths, the linear scaling relationship between k and time holds. Our theory sheds light on predicting permeability evolution in many geological settings when the self-enhancing process is relevant. References: Wang, L., and M. B. Cardenas (2017), Linear permeability evolution of expanding conduits due to feedback between flow and fast phase change, Geophys. Res. Lett., 44(9), 4116-4123, doi: 10.1002/2017gl073161.
EMI Modeling for UXO Detection and Discrimination Underwater
2011-12-01
detection and discrimination underwater,? submitted to the Strategic Environmental Research and Development Program (SERDP) in response to the...phenomena from highly conducting and permeable metallic objects in underwater environments, and 3) investigate the impact of the electromagnetic parameters of...to the Department of Defense Strategic Environmental Research and Development Program (SERDP). The publication of this report does not indicate
Towards Enhanced Performance Thin-film Composite Membranes via Surface Plasma Modification
Reis, Rackel; Dumée, Ludovic F.; Tardy, Blaise L.; Dagastine, Raymond; Orbell, John D.; Schutz, Jürg A.; Duke, Mikel C.
2016-01-01
Advancing the design of thin-film composite membrane surfaces is one of the most promising pathways to deal with treating varying water qualities and increase their long-term stability and permeability. Although plasma technologies have been explored for surface modification of bulk micro and ultrafiltration membrane materials, the modification of thin film composite membranes is yet to be systematically investigated. Here, the performance of commercial thin-film composite desalination membranes has been significantly enhanced by rapid and facile, low pressure, argon plasma activation. Pressure driven water desalination tests showed that at low power density, flux was improved by 22% without compromising salt rejection. Various plasma durations and excitation powers have been systematically evaluated to assess the impact of plasma glow reactions on the physico-chemical properties of these materials associated with permeability. With increasing power density, plasma treatment enhanced the hydrophilicity of the surfaces, where water contact angles decreasing by 70% were strongly correlated with increased negative charge and smooth uniform surface morphology. These results highlight a versatile chemical modification technique for post-treatment of commercial membrane products that provides uniform morphology and chemically altered surface properties. PMID:27363670
NASA Astrophysics Data System (ADS)
Xu, Yonggang; Yuan, Liming; Zhang, Deyuan
2016-04-01
A silicone rubber composite filled with carbonyl iron particles and four different carbonous materials (carbon black, graphite, carbon fiber or multi-walled carbon nanotubes) was prepared using a two-roller mixture. The complex permittivity and permeability were measured using a vector network analyzer at the frequency of 2-18 GHz. Then a type-based mixing rule based on the dielectric absorbent and magnetic absorbent was proposed to reveal the enhancing mechanism on the permittivity and permeability. The enforcement effect lies in the decreased percolation threshold and the changing pending parameter as the carbonous materials were added. The reflection loss (RL) result showed the added carbonous materials enhanced the absorption in the lower frequency range, the RL decrement value being about 2 dB at 4-5 GHz with a thickness of 1 mm. All the added carbonous materials reinforced the shielding effectiveness (SE) of the composites. The maximum increment value of the SE was about 3.23 dB at 0.5 mm and 4.65 dB at 1 mm, respectively. The added carbonous materials could be effective additives for enforcing the absorption and shielding property of the absorbers.
Pandey, S N; Vishal, Vikram
2017-12-06
3-D modeling of coupled thermo-hydro-mechanical (THM) processes in enhanced geothermal systems using the control volume finite element code was done. In a first, a comparative analysis on the effects of coupled processes, operational parameters and reservoir parameters on heat extraction was conducted. We found that significant temperature drop and fluid overpressure occurred inside the reservoirs/fracture that affected the transport behavior of the fracture. The spatio-temporal variations of fracture aperture greatly impacted the thermal drawdown and consequently the net energy output. The results showed that maximum aperture evolution occurred near the injection zone instead of the production zone. Opening of the fracture reduced the injection pressure required to circulate a fixed mass of water. The thermal breakthrough and heat extraction strongly depend on the injection mass flow rate, well distances, reservoir permeability and geothermal gradients. High permeability caused higher water loss, leading to reduced heat extraction. From the results of TH vs THM process simulations, we conclude that appropriate coupling is vital and can impact the estimates of net heat extraction. This study can help in identifying the critical operational parameters, and process optimization for enhanced energy extraction from a geothermal system.
KGS-HighK: A Fortran 90 program for simulation of hydraulic tests in highly permeable aquifers
Zhan, X.; Butler, J.J.
2006-01-01
Slug and pumping tests (hydraulic tests) are frequently used by hydrogeologists to obtain in-situ estimates of the transmissive and storage properties of a formation (Streltsova, 1988; Kruseman and de Ridder, 1990; Butler, 1998). In aquifers of high hydraulic conductivity, hydraulic tests are affected by mechanisms that are not considered in the analysis of tests in less permeable media (Bredehoeft et al., 1966). Inertia-induced oscillations in hydraulic head are the most common manifestation of such mechanisms. Over the last three decades, a number of analytical solutions that incorporate these mechanisms have been developed for the analysis of hydraulic tests in highly permeable aquifers (see Butler and Zhan (2004) for a review of this previous work). These solutions, however, are restricted to a subset of the conditions commonly encountered in the field. Recently, a more general solution has been developed that builds on this previous work to remove many of the limitations imposed by these earlier approaches (Butler and Zhan, 2004). The purpose of this note is to present a Fortran 90 program, KGS-HighK, for the evaluation of this new solution. This note begins with a brief overview of the conceptual model that motivated the development of the solution of Butler and Zhan (2004) for pumping- and slug-induced flow to/from a central well. The major steps in the derivation of that solution are described, but no details are given. Instead, a Mathematica notebook is provided for those interested in the derivation details. The key algorithms used in KGS-HighK are then described and the program structure is briefly outlined. A field example is provided to demonstrate program performance. The note concludes with a short summary section. ?? 2005 Elsevier Ltd. All rights reserved.
Hydraulic fracturing to enhance the remediation of DNAPL in low permeability soils
DOE Office of Scientific and Technical Information (OSTI.GOV)
Murdoch, L.; Slack, B.
1996-08-01
Meager rates of fluid flow are a major obstacle to in situ remediation of low permeability soils. This paper describes methods designed to avoid that obstacle by creating fractures and filling them with sand to increase well discharge and change paths of fluid flow in soil. Gently dipping fractures 10 m in maximum dimension and 1 to 2 cm thick can be created in some contaminated soils at depths of a few in or greater. Hydraulic fractures can also be used to create electrically conductive layers or to deliver granules of chemically or biologically active compounds that will degrade contaminantsmore » in place. Benefits of applying hydraulic fractures to DNAPL recovery include rates of fluid recovery, enhancing upward gradients to improve hydrodynamic stabilization, forming flat-lying reactive curtains to intersect compounds moving downward, or improving the performance of electrokinetics intended to recover compounds dissolved in water. 30 refs., 7 figs., 1 tab.« less
NASA Astrophysics Data System (ADS)
Pereira, Tatiana Aparecida; Ramos, Danielle Nishida; Lopez, Renata F. V.
2017-03-01
Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs). In this work, hydrogels with different zeta potentials were used as the coupling medium for LFU to investigate their contribution to LTR patterns and to the skin penetration of two model drugs, calcein and doxorubicin (DOX). When hydrogels were used, LTRs covering at least a 3-fold greater skin area were observed compared to those resulting from traditional LFU treatment and sodium lauryl sulfate. More LTRs resulted in an enhancement of calcein skin permeation. The zeta potential of the hydrogels affected the skin penetration of the positively charged DOX; the cationic coupling medium decreased the DOX recovered from the viable epidermis by 2.8-fold, whereas the anionic coupling medium increased the DOX accumulation in the stratum corneum by 4.4-fold. Therefore, LFU/hydrogel treatment increases LTRs areas and can target ionized drugs to specific skin layers depending on the zeta potential of the coupling medium.
Carbon-based sputtered coatings for enhanced chitosan-based films properties
NASA Astrophysics Data System (ADS)
Fernandes, C.; Calderon V., S.; Ballesteros, Lina F.; Cerqueira, Miguel A.; Pastrana, L. M.; Teixeira, José A.; Ferreira, P. J.; Carvalho, S.
2018-03-01
In order to make bio-based packaging materials competitive in comparison to petroleum-based one, some of their properties need to be improved, among which gas permeability is of crucial importance. Thus, in this work, carbon-based coatings were applied on chitosan-based films by radiofrequency reactive magnetron sputtering aiming to improve their barrier properties. Chemical and morphological properties were evaluated in order to determine the effect of the coatings on the chemical structure, surface hydrophobicity and barrier properties of the system. Chemical analysis, performed by electron energy loss spectroscopy and Fourier transform infrared spectroscopy, suggests similar chemical characteristics among all coatings although higher incorporation of hydrogen as the acetylene flux increases was observed. On the other hand, scanning transmission electron microscopy revealed that the porosity of the carbon layer can be tailored by the acetylene flux. More importantly, the chitosan oxygen permeability showed a monotonic reduction as a function of the acetylene flux. This study opens up new opportunities to apply nanostructured coatings on bio-based polymer for enhanced oxygen barrier properties.