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Sickle cell anemia is a hematological disorder that is caused by a single point mutation in the beta-globin chain of hemoglobin. It results in several complications related to the small and large vessels in patients with the disease. Large vessel complications include cerebral infarcts, which are observed in children under ten years old. The mechanism behind this complication is not completely understood. It is the goal of this project to begin to understand the role sickle erythrocytes may play in causing endothelial dysfunction as a precursor to sickle related complications. The hypothesis of this work is that exposure of large vessel endothelium to sickle erythrocytes causes an increase in endothelial permeability through loosening of adherens junctions. In the first goal of this work, bovine aortic endothelial cells (BAECs) are grown on coverslips and exposed to sickle erythrocytes for 5 minutes and either immediately fixed or incubated in 30 minutes and then fixed. Immunofluorescent studies labeling VE cadherin show changes in VE cadherin dynamics, suggesting sickle erythrocytes may be involved in this observation. Next, BAECs were grown on transwell inserts and exposed to sickle erythrocytes for 5 minutes. The erythrocytes are washed off and the BAEC are incubated with 10,000 MW dextran conjugated to lucifer yellow or FITC-BSA or to determine BAEC permeability. When dextran is used as the test molecule, endothelial permeability did not show a significant change from baseline. However, when BSA is used as the test molecule, increases in endothelial permeability are observed. Explanations into the differences between the transport mechanisms of the two molecules are discussed. These experiments show changes in VE cadherin localization due to sickle erythrocyte exposure. This may cause increases in endothelial permeability and an experimental model and preliminary studies are performed. This study provides potential mechanisms to explain the changes in VE cadherin localization and provide suggestions for further studies to test the effect of sickle erythrocytes on endothelial permeability. This work provides a strong foundation for continuing studies on the effects of sickle erythrocytes on endothelial dysfunction within the confines of sickle related complications.

The operation of pulse tube cryocoolers (PTCs) is based on complicated and poorly-understood solid-fluid interactions involving periodic flows of a cryogenic fluid in a flow loop that includes components filled with micro porous structures. CFD simulation is the current trend in modeling of pulse-tube cryocoolers. Such simulations can only be meaningful if correct closure relations are available. The objective of this investigation is to measure and empirically correlate the axial hydrodynamic parameters for two widely used cryocooler regenerator structures. A test section will be designed, constructed and instrumented for the measurements. Porous structures tested will include 325 and 400-Mesh stainless screens, each at two different porosities. Tests will be performed with helium as the working fluid, over a wide range of parameters. The longitudinal permeabilities and Forchheimer s inertial coefficients will then be obtained in an iterative process where agreement between the data and the predictions of detailed CFD simulations for the entire test sections and their vicinity are sought. Empirical correlations representing the longitudinal permeability and Forchheimer s coefficient in terms of relevant dimensionless parameters will then be developed.

The aim of the study is to investigate the causal relationship between membrane-damaging activity and antibacterial action of cardiotoxins from Naja naja atra (Taiwan cobra) cardiotoxin 3 (CTX3) and Naja nigricollis (Egyptian cobra) toxin gamma. Compared with that on Escherichia coli (E. coli, Gram-negative bacteria), CTX3 showed a greater growth inhibition on Staphylococcus aureus (S. aureus, Gram-positive bacteria). Antibacterial avtivity of toxin gamma toward E. coli and S. aureus was similar. Bactericidal action of cardiotoxins positively correlated with increase in membrane permeability of bacterial cells. Morphological examination showed that cardiotoxins disrupted the integrity of bacterial membrane. Cardiotoxins showed similar binding capability with lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and destabilization of LPS layer and inhibition of LTA biosynthesis on cell wall promoted bactericidal effect of cardiotoxins on E. coli and S. aureus, respectively. CTX3 notably permeabilized model membrane of S. aureus and toxin gamma had similar activity on the permeabilization of bacterial model membrane used. Membrane-damaging activity of cardiotoxins was inhibited by either LPS or LTA, while increasing concentrations of cardiotoxins counteracted the inhibitory action of LPS and LTA. Oxidation of Met residues on loop II of cardiotoxins simultaneously attenuated membrane-permeabilizing activity and bactericidal effect of cardiotoxins. Taken together, our data indicate that antibacterial action of cardiotoxins depend on their ability to induce membrane permeability.

In the coming decades, the world will require additional supplies of natural gas to meet the demand for energy. Tight gas reservoirs can be defined as reservoirs where the formation permeability is so low (< 0.1 md) that advanced stimulation technologies, such as large volume fracture treatments, are required before a reasonable profit can be made. Hydraulic fracturing is one of the best methods to stimulate a tight gas well. Most fracture treatments result in 3-6 fold increases in the productivity index. However, if one computes the effective fracture length of most wells, we usually find that the effective length is less than the designed propped fracture length. The “propped length” is the distance down the fracture from the wellbore where proppants have been placed at a high enough concentration to “prop open” the fracture. The “effective length” is the portion of the propped fracture that cleans up and allows gas flow from the reservoir into the fracture then down the fracture to the wellbore. Whenever the effective length is much shorter than the designed propped length, several reasons must be evaluated to determine what might have occurred. For example, the difference could be caused by one or more of the following issues: insufficient fracture fluid cleanup, proppant settling, proppant embedment, proppant crushing, or poor reservoir continuity. Although all these causes are possible, we believe that fracture fluid cleanup issues may be the most common reason the industry fails to achieve the designed propped fracture length in most cases. In this research, we have investigated fracture fluid cleanup problems and developed a better understanding of the issues involved which hopefully will lead to ways to improve cleanup. Fracture fluid cleanup is a complex problem, that can be influenced by many parameters such as the fluid system used, treatment design, flowback procedures, production strategy, and reservoir conditions. Residual polymer in the fracture can reduce the effective fracture permeability and porosity, reduce the effective fracture half-length, and limit the well productivity. Our ability to mathematically model the fundamental physical processes governing fluid recovery in hydraulic fractures in the past has been limited. In this research, fracture fluid damage mechanisms have been investigated, and mathematical models and computer codes have been developed to better characterize the cleanup process. The codes have been linked to a 3D, 3-phase simulator to model and quantify the fracture fluid cleanup process and its effect on long-term gas production performances. Then, a comprehensive systematic simulation study has been carried out by varying formation permeability, reservoir pressure, fracture length, fracture conductivity, yield stress, and pressure drawdown. On the basis of simulation results and analyses, new ways to improve fracture fluid cleanup have been provided. This new progress help engineers better understand fracture fluid cleanup, improve fracture treatment design, and increase gas recovery from tight sand reservoirs, which can be extremely important as more tight gas reservoirs are developed around the world.

This study investigates the changes due to crosslinking treatment in stiffness, permeability, and glycosaminoglycan (GAG) content of bovine intervertebral discs. The objective of this study was to determine the mechanical and biochemical effects of crosslinking treatment on lumbar bovine tissue. Previous studies have found that crosslinking can increase stiffness and permeability in the intervertebral disc. These changes have not yet been investigated by confined compression, stress-relaxation tests of young bovine tissue. Eleven lumbar motion segments were harvested from calf spines and soaked in a saline solution or one of four crosslinking treatments (genipin, methylglyoxal, proanthrocyanidin, and EDC). Five mm diameter samples were removed from the midannulus region at anterior / anterior-lateral locations, confined in a saline bath, swelled to equilibrium, and tested in confined compression stress-relaxation to 15% strain in 5% increments. Radial samples were also harvested, treated with saline solution and EDC, and tested in the same manner. The aggregate modulus and hydraulic permeability were calculated using the nonlinear biphasic theory. Swelling pressure was calculated as the load at swelling equilibrium. GAG content was measured using the dimethylmethylene blue assay. Differences with P value < 0.05 were considered significant. In the axial orientation, all crosslinking treatments except methyglyoxal at least doubled the aggregate modulus relative to soaked controls (P less than 0.05). Genipin treatment resulted in 78% lower axial permeability, proanthrocyanidin (PA) 50% lower, and EDC treatment 84% lower relative to soaked controls (P &lt; 0.05). GAG content measured in the methyglyoxal treatment group was 25% lower than in soaked control group. Genipin (G), proanthrocyanidin (PA), and EDC treatment increased the swelling pressure by at least 65% (P less than 0.05). In the radial orientation, EDC treatment increased the stiffness by 75%, and did not significantly affect the permeability or swelling pressure. Some crosslinking treatments proved effective in increasing the stiffness and swelling pressure of the disc. The increased swelling pressure in G, PA, and EDC treatment groups relative to soaked controls suggests reduced GAG leaching during soaking treatment, further confirmed by the reduction in permeability in these groups.

The Woodlands, Texas, is a 27,000-acre new town created with Ian McHarg's ecohydrological planning approach. The Woodlands is the best example of ecologically based new town planning in the United States during the 1970s. The Woodlands survived storms in excess of one-hundred-year levels in 1979 and 1994 with little property damage, while Houston, 31 miles away, was severely flooded in both events. For the past three decades, very few studies have been conducted to assess the effectiveness of McHarg's planning approach. The objective of this study is three fold: (1) To document McHarg's ecohydrological planning concepts, implementation and unveil the barriers to continue his approach; (2) To compare flood mitigation effectiveness of different drainage systems used in The Woodlands development; and (3) To simulate "what if" land-use scenarios using different planning approaches. Original development information is collected from published monographs, journal articles, newspapers and designers' collections. Geographic Information System (GIS) parcel data are obtained from Montgomery County Appraisal District. Streamflow data are acquired from the USGS website. Weather data are downloaded from the NOAA website. Land use and land cover data are collected from various national datasets. Two GIS hydrologic models--the Soil and Water Assessment Tool (SWAT) and the Kinematic Runoff and Erosion model (KINEROS)--are used for watershed simulation. The statistic analysis tool SPSS is used for correlation analysis. Results show that McHarg's planning approach was followed in the early phases of development (1974-1996) but was largely abandoned in the later phases when its ownership was changed in 1997. McHarg's approach ceased to be implemented because of the low public acceptance of ecohydrological planning strategies and the conflicts between short-term investment return and long-term environmental stewardship. In addition, comparative study shows that the early phases of development responded to rainfall similarly to its pre-development forest conditions. However, the later phases generated runoff volumes three times greater than the early phases. Therefore, McHarg's ecohydrological planning approach demonstrates flood mitigation effectiveness that is superior to the conventional approach. Finally, using soil permeability to coordinate development density and land use presents a viable solution for mitigating environmental impacts from a stormwater perspective.

Frictional measurements were made on natural fault gouge at seismic slip rates using a high-speed rotary-shear apparatus to study effects of slip velocity, acceleration, displacement, normal stress, and water content. Thermal-, mechanical-, and fluid-flowcoupled FEM models and microstructure observations were implemented to analyze experimental results. Slightly sheared starting material (Unit 1) and a strongly sheared and foliated gouge (Unit 2) are produced when frictional heating is insignificant and the coefficient of sliding friction is 0.4 to 0.6. A random fabric gouge with rounded prophyroclasts (Unit 3) and an extremely-fine, microfoliated layer (Unit 4) develop when significant frictional heating occurs at greater velocity and normal stress, and the coefficient of sliding friction drops to approximately 0.2. The frictional behavior at coseismic slip can be explained by thermal pressurization and a temperature-dependent constitutive relation, in which the friction coefficient is proportional to 1/T and increases with temperature (temperature-strengthening) at low temperature conditions and decreases with temperature (temperature-weakening) at higher temperature conditions. The friction coefficient, normal stress, pore pressure, and temperature within the gouge layer vary with position (radius) and time, and they depend largely on the frictional heating rate. The critical displacement for dynamic weakening is approximately 10 m or less, and can be understood as the displacement required to form a localized slip zone and achieve a steady-state temperature condition. The temporal and spatial evolution of hydromechanical properties of recovered from the Nankai Trough (IODP NanTroSEIZE Stage 1 Expeditions) have been investigated along different stress paths, which simulate the natural conditions of loading during sedimentation, underthrusting, underplating, overthrusting, and exhumation in subduction systems. Porosity evolution is relatively independent of stress path, and the sediment porosity decreases as the yield surface expands. In contrast, permeability evolution depends on the stress path and the consolidation state, e.g., permeability reduction by shear-enhanced compaction occurs at a greater rate under triaxialcompression relative to uniaxial-strain and isotropic loading. In addition, experimental yielding of sediment is well described by Cam-Clay model of soil mechanics, which is useful to better estimate the in-situ stress, consolidation state, and strength of sediment in nature.

Summary Clmatis Armandi has been used frequently in traditional Chinese medicine for the treatment of diuretic symptoms. The mechanism of its action is unclear. Possible action of this substance may involve alternation of electrolyte transport through the epithelia membranes. In this study¡Atransepithelial conductance of frog skin was measured in vitro in voltage-clamped Ussing chambers. Adding Clematis Armandi extracts to apical surface induced a conductance increment of 1.21 £gS and an apical to serosal Isc of 28.78 £gA/cm2. The Isc can not be completely blocked by apical application of amiloride. Nifedipine and TEA had no effect on Clematis Armandi induced Isc decrease. These data indicate that frog skin is highly responsive to the concentrated Clematis Armandi extracts. The increase in Isc reflects changes in transepithelial transport of Na+ ions modulated at apical membrane. The enormous increase in transepithelial conductance suggests that in additional to enhancement of amiloride-sensitive Na+ channels, Clematis Armandi may also modulate other pathways, such as Cl- ion channel modulation, which needs further investigation.