Endotoxin (lipopolysaccharide, LPS) a chemical component of cell wall of gram-negative bacteria, is an important mediator in pathogenesis of sepsis and acute respiratory distress syndrome. It causes production and release of a wide array of mediators including cytokines, chemokines, oxygen free radicals and nitric oxide from neutrophils, macrophages, endothelial cells and epithelial cells through the NF-£eB pathway. LPS increases the permeability of microcirculation, and causes the acute formation of numerous endothelial gaps among venular endothelial cells, resulting in extensive plasma leakage in the inflammatory tissue. Urethan is commonly used as an animal anesthetic for nonrecovery laboratory surgery. It is aslo an £\2-adrenoreceptor antagonist, which can suppress the activation of the cardiovascular system and reduce the angiotensin which increases the blood pressure. Urethan or its metabolites protect animals against LPS, in part, by reducing TNF-£\ release. The aims of the present study to investigate the time-course of vascular permeability in microcirculation of rat trachea, bronchus and esophagus after intravenous application of a high dose of LPS (15 mg/kg), and to reveal the role of urethan (1 g/¢V) and dimethylthiourea (DMTU, 0.375 g/¢V) in inhibition of LPS-induced plasma leakage and edema. India ink was used as a tracer dye to mark leaky microvessels after LPS application. Endothelial gaps were made visible for light microscopy by staining the borders of endothelial cells with silver nitrate. Tracheal sections were stained with toluidine blue to show the subendothelial edema formation. A high dose of LPS was administered intravenously to induce serious plasma leakage and edema and a large number of endothelial gaps formed in postcapillary and collecting venules in the rat trachea and esophagus. The peak values of plasma leakage and edema occurred 5 min after LPS (P<0.01). Urethan anesthesia significantly inhibited LPS-induced plasma leakage by 95 ¡Ó 1.7% in various parts of the respiratory tracts and inhibited edema ratio in the trachea by 57%. Urethan was also found to reduce leukocyte infiltration and the number of endothelial gaps by 46.8 ¡Ó 4.6%. DMTU pretreatment significantly inhibited plasma leakage by 88.5 ¡Ó 2.5% in the respiratory tract and inhibited edema ratio in the trachea by 89% at 5 min after LPS. It is concluded that LPS-induced increase in plasma leakage and edema correlated with the formation of endothelial gaps, and association with activation of alpha 2-adrenergic receptors and hydroxyl free radical production.

Stimulation of C-fiber sensory neurons innervating the respiratory tract with electricity or capsaicin leads to the liberation of substance P, CGRP and other neuropeptides from the nerve terminals. Substance P (SP) binds to the NK-receptors on the membrane of vascular endothelial cells and elicits neurogenic inflammatory responses. These inflammatory responses include plasma leakage and the subsequent edema formation (Lundberg and Saria, 1983¡FMcDonald et al., 1988). Evans blue is a hydrophilic dye and is often used as a tracer of plasma leakage due to its¡¦ high affinity to the plasma proteins. Plasma leakage causes Evans blue extravasates from the blood vessels and remains in the tissues. The more plasma leaks from the blood vessels, the more Evans blue will extravasate into the tissues. Measuring extravasated Evans blue dye that is extracted from tissues, is useful for evaluation of the amount of plasma leakage. Potassium channel openers can inhibit neurogenic plasma leakage in the airways and urinary bladder (Hollywood et al., 1998). Evans blue directly stimulates large-conductance Ca2+-activated K+ channels in cultured endothelial cells of human umbilical vein (Wu et al., 1999). This suggests that it may influence the permeability of the microvessels in vivo. A previous study shows that Evans blue dye blocks capsaicin-induced cough and bronchospasm in the guinea pig (Bolaer et al., 1995). We postulated that pretreatment with Evans blue may influence the extent of neurogenic inflammation in the rat airways induced by the application of either SP or capsaicin. India ink was used as a colloidal tracer dye to label the leaky vessels. The present study investigated whether different concentration of Evans blue (0, 3, 15 and 30 mg/ml/kg) pretreatment could affect the plasma leakage and edema formation in rat lower airways in response to intravenous injection of either SP or capsaicin. The amount of plasma leakage was expressed by the area density of India ink-labeled leaky blood vessels. We also investigated whether Evans blue influenced the ultra-structural change in tracheal serous cells induced by intravenous injection of SP. Our results showed that pretreatment with high concentration of Evans blue reduced more than seven tenths of the area density of plasma leakage in the trachea caused by SP application (P<0.01); reduced more than seven tenths in the left main bronchus (P<0.01) and reduced about seven tenths in the right main bronchus (P<0.01), compared to the control group that received saline prior to SP. However, no statistical significance was observed in edema ratio between any two groups (P>0.05). In the neurogenic inflammation of the airways caused by injection of capsaicin, pretreatment with high concentration of Evans blue reduced more than seven tenths of the area density of plasma leakage in the trachea (P<0.01); reduced more than seven tenths in the left main bronchus (P<0.01) and reduced about seven tenths in the right main bronchus (P<0.01), respectively, compared to the control group that received saline prior to capsaicin. Pretreatment with high concentration of Evans blue prior to capsaicin also reduced more than eight-tenth in edema ratio (P<0.01). In the ultra-structure change of serous cells and the stastical analysis of the number of active serous per 1000£gm2 of tracheal epithelium, Evans blue pretreatment prior to SP significantly reduced the number of active serous cells by seven tenths (P<0.01) as compared to control group that received saline prior to SP. Therefore, we concluded that pretreatment with high concentration of Evans blue exerted its¡¦ effect by opening large-conductance Ca2+-activated K+ channels and inhibited the plasma leakage induced by SP or capsaicin. But no significant inhibition was observed in edema formation induced by SP application. Low concentration of Evans blue might enhance the neurogenic inflammation of the airway. Under the observation with SEM, we found that SP activated serous cells in airway epithelium, and high concentration of Evans blue pretreatment lowered the secretory activity of serous cells. Therefore Evans blue might inhibit the activation of serous cells.

The mechanisms underlying the 6-hydroxydopamine (6-OHDA)-induced inflammatory response in the urinary bladder and prostate in anaesthetized male rats of Long- Evan strain were investigated. The magnitude of inflammatory responses were evaluated by morphometric analysis of the area density of India ink-labeled blood vessels in urinary bladder whole mounts and spectrophotometric analysis of Evans blue dye contents in urinary bladder and prostate. Moreover, scanning electron microscopy was employed to observe the venular endothelium in the urinary bladder wall and glandular epithelium in the prostate gland. Fifteen minutes after local application of 6-OHDA to the urinary bladder, 6-OHDA induced an increase of plasma leakage in a dose-dependent manner. It was revealed that area densities of India ink-labeled blood vessels in the rat urinary bladder whole mount were 5.65¡Ó1.72 % (N=6), 22.63¡Ó3.12 % (N=6), and 35.02¡Ó2.25 % (N=6) respectively, following a local injection of vehicle, 5 mg/kg 6-OHDA, and 10 mg/kg 6-OHDA. Using Evans blue dye as a tracer for spectrophotometric analysis, the results were similar. The Evans blue dye content was 80.53¡Ó60.74 ng/mg in the urinary bladder and 48.81¡Ó2.83 ng/mg in the prostate following injection of 5 mg/kg 6-OHDA (N=6). The Evans blue dye content was 157.73¡Ó4.45 ng/mg in the bladder and 65.52¡Ó4.25 ng/mg in the prostate following injection of 10 mg/kg 6-OHDA (N=6). Evans blue dye contents in the vehicle group (N=6) were much lower, 18.82¡Ó3.74 ng/mg in the urinary bladder and 18.50¡Ó2.47 ng/mg in the prostate, which were significantly smaller than the 6-OHDA treated group. Interestingly, the inflammatory responses were completely abolished by pretreating alone with dimethylthiourea (DMTU), a hydroxyl radical scavenger, and were moderately attenuated by pretreatment with L-732,138, a NK1 receptor antagonist. Under scanning electron microscope observation, 6-OHDA caused endothelial gaps formation in the venules of urinary bladder wall and triggered the release of secretory granules in the prostate gland cells. We concluded that 6-OHDA could induce inflammation in the urinary bladder and prostate gland involving free radical and tachykinin mechanisms.

¡iAbstract¡j Lipopolysaccharide (LPS) is the toxic chemical component of the cell wall in all gram-negative bacteria which can stimulate immune cells, including macrophages and white blood cell, to release cytokines such as interleukin-1£], interleukin-6 and tumor necrosis factor-£\. These pro-inflammatory mediators induce systemic acute inflammation and multiple organs dysfuction syndrome in sepsis. Plasma leakage from microvasculature is a hallmark of inflammation. Previous studies have demonstrated that other inflammatory agents, such as capsaicin, substance P and histamine could cause the acute formation of numerous endothelial gaps in the venules that result in extensive plasma leakage in the inflammatory tissues of the whole respiratory tract and a part of digestive tract in a few minutes. Mammalian intestines have many goblet cells that synthesize mucus and discharge it into the intestinal lumen. The mucus film that covers the surface epithelium facing the lumen of digestive system, is an immune defense that can prevent gastrointestinal epithelium from chemical and physical damage and act as a lubricant. Changes in goblet cell function and number are involved in microbial infection, inflammatory syndromes and immune factors. This study was aimed to investigate: (1) The degree of Plasma leakage and goblet cell hypersecretion in the small intestine of rats after an intravenous injection of a high dose of LPS (15 mg/kg), and (2) The involvement of vagus nerve and cholinergic receptors in plasma leakage and goblet cell secretion. For the study of plasma extravasation in small intestine during endotoxema, India ink was used as the tracer to mark the inflamed leaky microvessels. Rats were perfusion-fixed through the aorta, and endothelial gaps between endothelial cells of blood vessels were made visible with silver staining. The methacrylate sections of the ileum 3 £gm in thickness were stained with Alcian blue and periodic acid-schiff reagent to detect glycoproteins of goblet cells. Our results showed that LPS not only caused an increase in plasma leakage but also triggered degranulation of many goblet cells in villi and crypts. Numerous gaps were found in postcapillary venules and collecting venules, and plasma extravasation was observed in the serosa and tunica muscularis rat small intestine after LPS. Extensive plasma extravasation occurred in earier phases (5-30 min). However, numerous goblet cells started to discharge mucus granules 30 min after LPS treatment. A large amount of extracellular mucus was accumulated between intestinal villi 1 hour after LPS stimulation. Pretreatment with atropine, the muscarinic receptor antagonist, significantly inhibited goblet cell secretion. The inhibitory effect of pretreatment with atropine or bilateral cervical vagotomy on LPS-induced plasma leakage was not consistent. It is concluded that the plasma leakage and goblet cell hypersecretion induced by endotoxin shock was time-dependent and was associated with activation of muscarinic cholinergic receptors.

This thesis provides a comparison of experimental rotordynamic coefficients for laminar, smooth bushing oil seals to theoretical predictions from XLLubeGT and XLAnSeal. The experimental results come from a new test rig developed at the Turbomachinery Laboratory at Texas A&M University. The two software programs were developed to predict the static and dynamic characteristics of seals. XLLubeGT is a Reynolds equation based program while XLAnSeal is based on a bulk-flow Navier- Stokes model that includes temporal and convective acceleration terms. XLAnSeal was used to predict the added-mass terms of the seals since XLLubeGT assumes those terms to be zero or negligible. The data used for input into the two seals code was the actual measured conditions from the test rig. As part of the input parameters, inlet inertia effects and thermal gradients along the seal were included. Both XLLubeGT and XLAnSeal have the capability to analyze straight bore seals with different inlet and outlet clearances – essentially a tapered seal – but seal expansion caused by the radial differential pressure across the seal bushing was not included. Theoretical and experimentally determined dynamic characteristics include stiffness, damping, inertia terms and Whirl Frequency Ratio (WFR). Seal static characteristics are also reported. They include: leakage, shaft center line loci and Reynolds numbers. Test conditions include three shaft speeds: 4000, 7000 and 10,000 rpm, three test pressures: 21, 45 and 69 bar [300, 650, and 1000 psi] and multiple eccentricities from 0.0 to 0.7. The results for the dynamic characteristics show good correlation of the experimental data to the theoretical values up to an eccentricity of about 0.5. At higher eccentricities, the theory generally under-predicts the dynamic characteristics. Inertia terms are greatly under-predicted. The results for the static characteristics also show good correlation to the experimental data, but they also have a tendency to be under-predicted at higher eccentricities.

This dissertation analyzes the basis for and magnitudes of discount factors based on the characteristics of greenhouse gas emission (GHGE) offsets that are applied to the GHGE reduction projects, concentrating on agricultural projects. Theoretical approaches to discount factors, estimation and incorporation of discount factors procedures are developed. Discount factors would be imposed by credit purchasers due to noncompliance with regulatory program of the credits with GHG program including consideration of shortfall penalties and limited durations. Discount factors are proposed for (i) additionality, (ii) leakage, (iii) permanence, and (iv) uncertainty. Additionality arise when the region where an AO project is being proposed would have substantial adoption of the AO practice in the absence of GHG programs (business as usual GHGE offset). Leakage arises when the effect of a program is offset by an induced increase in economic activity and accompanying emissions elsewhere. The leakage effect depends on demand and supply elasticities. Permanence reflects the saturation and volatility characteristics of carbon sequestration. Carbon is stored in a volatile form and can be released quickly to the atmosphere when an AO practice is discontinued. The permanence discount depends on the project design including practice continuation after the program and the dynamic rate of offset. Also, consideration of multiple offsets is important. Uncertainty arises due to the stochastic nature of project quantity. The uncertainty discount tends to be smaller the larger the size of the offset contract due to aggregation over space and time. The magnitude of these discounts is investigated in Southeast Texas rice discontinuation study. The additionality and the leakage discounts are found to play an important role in case of rice lands conversion to other crops but less so for pasture conversions and yet less for forest conversions. The permanence discount is important when converting to other crops and short rotation forestry. When all discounts are considered, rice lands conversion to forest yields claimable credits amounting to 52.8% ~ 77.5% of the total offset. When converting rice lands to pasture, the claimable credits 45.1% ~ 64.2%, while a conversion of rice lands to other crops yields claimable credits 38.9% ~ 40.4%.

Systematic parametric studies were performed to better understand seal-inlet rotordynamics. A CFD-perturbation model was employed to compute the seal-inlet flow disturbance quantities. Seal inlet disturbance boundary condition correlations were proposed from the computed seal-inlet quantities using the important parameters. It was found that the cosine component of the seal-inlet swirl velocity disturbance W1C has a substantial impact on the cross-coupled stiffness, and that the correlations for W1C and W1S should be used to replace the historical guess that seal inlet W1C = 0 and W1S = 0. Also, an extremely precise relationship was found between the swirl disturbance W1C and the seal-inlet swirl velocity (ωRsh − ¯W0). Thus, the number of experiments or computer runs needed to determine the effect of spin speed, shaft radius and/or inlet swirl velocity on the cross-coupled stiffness is greatly reduced by plotting the simplified relationship of the cross-coupled stiffness against the swirl slip velocity. The benefits of using the new seal-inlet boundary condition correlations were assessed by implementing them into a CFD-perturbation model. Consistently improved agreement with measurements was obtained for both liquid annular seals and gas labyrinth seals. Further, the well-established CFD-perturbation model with new boundary condition correlations was employed to investigate the rotordynamics of two off-design situations. The first case considered the influence of labyrinth seal teeth damage on the performance and the rotordynamic characteristics of impeller eye seals in centrifugal compressors. The second case considered the influence of rotor-axial-shifting on rotordynamic forces for high-low labyrinth seals in steam turbines during the start-up and shut-down process. The results should provide useful information for labyrinth seal design and fault diagnosis of stability problems in turbines and compressors.

In order to construct the integrated circuit with high efficiency, the size of the semiconductor devices becomes smaller and smaller. The surface of the chip is unable to offer enough area for devices interconnecting, that the Ultra Large Scale Integration (ULSI) has to adopt the construction of multilayer metal conductor line, and to decrease it¡¦s connects. However, the RC delay time becomes a main issue to limiting semiconductor speed when the electron signal was transferred between two metal connects. In order to solve the problem of RC delay, and to lower resistivity, copper (1.7 £g£[-cm) is applied instead of Aluminum (2.7 £g£[-cm) at present. In additation, to lower the capacitance, the low-k material has taken place SiO for reducing the electric capacity. In this work, the capacitance and current of MIM(Metal-Insulator-Metal) of interconnecting circuit were investigated under bending stress. SiOC of OSG (Organic silicate glass) layer has applied to a MIM structure. In order to apply the strain in devices, the device was bended to a fixed curvature for compressed and tensile stress. By bending the device, the capacitance and leakage current I-V & C-V were analyzed and compared with the unstressed SAMPLE of I-V and C-V at high temperature, too. The result reveals both of Schottky and Poole-Frenkel conduction mechanism existing in device under a high electric field of 1800 V/cm1/2, which indicates the theoretical treatment is unappropriate for the interpretation of the leakage current mechanism.

Thesis (M.S.D.)--Indiana University School of Dentistry, 2009. / Title from PDF t.p. (viewed Feb. 5, 2010) Advisor(s): Michael A. Cochran, Chair of the Research Committee, Armando E. Soto Rojas, Margherita R. Fontana, Timothy Carlson, Tien-Min Gabriel Chu. Curriculum vitae. Includes abstract. Includes bibliographical references (leaves 56-61).

Leakage of CO₂ saturated fluid along wellbores has critical implications for the feasibility of geologic CO₂ storage. Wells, which are ubiquitous in locations ideal for CO₂ storage, develop leaks (e.g. fractures) for many reasons and at different points in their age. Small leaks pose the most significant risk to geological CO₂ sequestration because they are difficult to detect and provide a direct pathway through which fluid can escape the storage formation. This dissertation shows that due to complex coupling between reaction and flow, leaking wells will tend to self-seal via secondary precipitation of calcium carbonate in the open pathway. Residence time, fluid reactivity, and initial fracture aperture all play a key role in determining the time required to seal the leakage pathway. To test the self-sealing hypothesis, laboratory experiments were conducted to inject reactive fluids into naturally fractured cement. Restriction of the leakage pathway, i.e., the fracture, was inferred from the relationship between flow rate and pressure differential. Precipitation was observed in both constant flow rate and constant pressure differential experiments. In the former precipitation resulted in an increasing pressure differential, while precipitation caused a decrease in flow rate in the latter. Analysis by electron microprobe and x-ray diffraction, and corroborated with effluent chemical analysis, showed that the reacted channel was depleted in calcium and enriched in silicon relative to the original material. The remaining silicon rich material prevents widening of the reacted channel and development a self-enhancing (e.g. wormhole) behavior. Self-limiting behavior is caused by calcium mixing with carbonate ions in high pH slow flow regions where local residence time is large and calcium carbonate is insoluble. Secondary precipitation initially develops next to the reacted channel and then across the fracture surface and is the source of pathway restriction and the self-sealing behavior. Results from the experiments are used to develop a simple analytical model to forecast well scale leakage. Future work is needed to test a broader range of experimental conditions (e.g. brine salinity, cement formulations, cement-earth interface, effect of CO₂ saturation, pressure, and temperature), to improve our understanding of both the fundamental behavior and the leakage model. / text