Non-dilute salt strength solutions occur in many near surface geologic environments. In order to better understand the occurrence and movement of the water and salt, mathematical models for this non-ideal fluid need to be developed. Initial boundary value problems may then be solved to predict behavior for comparison with observations. Using the principles of equilibrium reversible and irreversible thermodynamics, relationships describing the thermo-physics of non-dilute saline solutions in variably saturated porous media are investigated. Each of four central chapters investigates a particular aspect of the flow of saline solutions through porous media. The first chapter derives the general relationships describing the effects of salt on the vapor content in the gas phase and also on the liquid pressure. The second chapter summarizes an example using the new theory for sodium chloride (NaCl) from zero to saturated strength. Additional terms beyond the dilute approximation are shown to be more important in very dry, fine textured soils with significant salt content. The third chapter derives the salt corrections for Darcy-type flow laws for variably saturated porous media, and an example for NaCl is given. Agreement between theory and experimental data is good, though there appear to be some unaccounted for effects. These effects may be the result of ionic interaction of the salt with the loamy sand used, and/or the effect of hysteresis of the water content-pressure relationship. The final chapter investigates two fundamental assumptions commonly used in process thermodynamics when considering mixtures described by porous media, saline water, and moist air. The first assumption is that temperature is the generalized intensive variable associated with entropy. The second assumption is that the form of the differential of total energy is known a-priori. It is shown that the first assumption is suspect under some circumstances, and a generalized notion of how to select extensive variables for a given system is introduced for comparison with the second assumption. Examples comparing the "usual" and new theories are accomplished for ideal gases and for isotropic Newtonian liquids, with results being favorable except possibly for the Gibbs-Duhem Relation of the Newtonian liquid for the "usual" theory. / Graduation date: 2005

A. A study of Stichodactyla helianthus toxin’s potential to penetrate the buccal mucosa Introduction:  Buccal mucosa is an alternative route for drug administration and has advantages over other conventional routes by avoiding both enzymes in the gastro intestinal system and the hepatic first passage mechanism. Stichodactyla helianthus toxin (ShK) is a peptide toxin that blocks potassium channels in T lymphocytes and could be a future treatment for autoimmune diseases when finding a suitable way of administration. Aim:  The purpose of this part of the study was to develop a robust and reproducible assay for identification and quantification of ShK. The method was then employed for a proof of principle study; determining the concentration of ShK following an in vitro permeability experiment, to evaluate the potential of ShK penetrating the buccal mucosa in porcine tissue.  Materials and Methods:  An HPLC method was developed and validated. A piece of porcine buccal mucosa was used as a membrane because of its similarities with human buccal mucosa, and cinched in between a modified Ussing Chamber consisting of a donor and a receptor chamber. Samples were withdrawn from the receptor chamber to determine the amount of ShK that had penetrated the membrane. Results: The HPLC method developed for quantification of ShK demonstrated high accuracy and precision. No concentrations of ShK were able to be quantified from the receptor chambers. Conclusions:  A robust assay for quantification of ShK was developed but the results from the experiment indicated that ShK could not penetrate the buccal mucosa membrane. B. An investigation of the permeability alterations in the blood-brain barrier associated with Alzheimer’s disease   Introduction:  The blood brain barrier (BBB) protects the brain from potential dangerous substances by different barrier properties such as tight junctions and efflux transporters such as P-glycoprotein. Previous studies have showed that the barrier functions may be altered in Alzheimer’s disease and thereby increase the exposure to substances that are normally excluded from the brain parenchyma. This could be an issue regarding safety and toxicity of medications used among Alzheimer patients. Aim:  The aim of this part of the study was to investigate the difference in brain uptake of verapamil, digoxin, loperamide, propanolol, diazepam and sucrose between 3xTg-AD mice and wild type control mice. Materials and Methods: Female 3xTg-AD mice and control mice of the age 11.5-13.5 months were used. In Situ brain perfusion with radiolabeled substances (n=5-12) was performed and the brain uptake ratio of the substances was compared and statistically analyzed.  Results: No difference in the vascular volume was found when comparing 3xTg-AD with control mice. The ratio of diazepam was observed to be higher in the cortex and propranolol higher in the hippocampus, of 3xTg-AD mice. The uptake ratio of verapamil was higher in both the hippocampus and cortex of 3xTg-AD mice whereas digoxin appeared to be lower in the cortex of 3xTg-AD mice. There was no difference in uptake ratio of loperamide between 3xTg-AD and control mice. Conclusions:  This study in addition to previously executed studies in our laboratory, showed that the membrane thickness is age dependent in 3xTg-AD and that further studies needs to be conducted on the expression of P-glycoprotein in the BBB in 3xTg-AD and control mice.

<p>The aim of this study was to investigate the effect the plant matrix and the structure of the flavonoid (i.e. whether aglycone or glycoside) may have on the gastrointestinal uptake and metabolism of luteolin derivatives from Artemisia afra traditional plant medicine. Specifically, how these two factors influenced the intestinal uptake and disposition of luteolin derivatives in pure and in Artemisia afra plant extract forms were to be assessed by investigating the uptake and metabolism of the luteolin derivatives in human intestinal epithelial Caco-2 cells and the perfused rat intestinal loop. To realize this aim, the following were determined: (1) identification and characterization of major luteolin derivatives found in Artemisia afra, (2) the effect of the plant matrix on the uptake of luteolin derivatives in Artemisia afra aqueous-extract forms across the Caco-2 cell monolayer, (3) the effect of the plant matrix on the absorption and metabolism of luteolin derivatives in Artemisia afra aqueous-extract forms in the perfused rat small intestine, (4) the effect of gut contents on the uptake and metabolism of luteolin derivatives in intestinal loop and (5) the metabolic profiles of luteolin derivatives obtained for the pure solutions versus plant aqueous extract solutions in Caco-2 cells and the rat intestine.</p>

With  the  continuous  advances  in  microwave  technology,  microwave  components  and  related magnetic materials become more important in industrial environment. In order to further develop the microwave components, it is of interest to find new kinds of technologies and materials. Here, we  introduce  a  new  kind  of  material  --  amorphous  metallic  wires  which  could  be  used  in microwave  components,  and  use  these  wires  to  design  new  kinds  of  attenuators.  Based  on  the fundamental  magnetic  properties  of  amorphous  wires  and  transmission  line  theory,  we  design  a series of experiments focusing on these wires, and analyze all the experimental results.    Experimental  results  show  that  incident  and  reflected  signals  produce  interference  and  generate standing  waves  along  the  wire.  At  given  frequency,  the  insertion  attenuation  S21 [dB]  of  an amorphous wire increases monotonically with dc bias current. The glass cover will influence the  magnetic  domain  structure  in  amorphous  metallic  wires.  Therefore,  it  will  affect  the circumference  permeability  and  change  the  signal  attenuation.  It  is  necessary  to  achieve  the impedance  matching  by  coupling  to  an  inductor  and  a  capacitor  in  the  circuit.  The  impedance matching  makes  the  load  impedance  close  to  the  characteristic  impedance  of  transmission  line. The magnetic wire-based attenuator designed in this thesis work are characterized and compared to conventional pin-diode attenuator.

Recently, carbon dioxide injection into deep sea sediments has become one of the carbon dioxide mitigation methods since carbon dioxide hydrates are stable at the prevailing pressure and temperature conditions. The Black Sea, which is one of the major identified natural methane hydrate regions of the world, can be a good candidate for carbon dioxide storage in hydrate form. Injected carbon dioxide under the methane hydrate stability region will be in contact with methane hydrate which should be analyzed thoroughly in order to increase our understanding on the gaseous carbon dioxide and methane hydrate interaction. For the storage of huge amounts of CO2, geological structure must contain an impermeable barrier. In general such a barrier may consist of clay or salt. In this study, sealing efficiency of methane hydrate and long term fate of the CO2 disposal under the methane hydrate zone is investigated. In order to determine the interaction of CO2 and CH4 hydrate and the sealing efficiency of CH4 hydrate, experimental setup is prepared and various tests are performed including the CH4 hydrate formation in both bulk conditions and within sand particles, measurement of the permeability of unconsolidated sand particles that includes 30% and 50% methane hydrate saturations and injection of CO2 into the CH4 hydrate. Results of the experiments indicate that, presence of hydrate sharply decreases the permeability of the unconsolidated sand system and systems with hydrate saturations greater than 50% may act as an impermeable layer. Also, CO2-CH4 swap within the hydrate cages is observed at different experimental conditions. As a result of this study, it can be concluded that methane hydrate stability region in deep sea sediments would be a good alternative for the safe storage of CO2. Therefore, methane hydrate stability region in the Black Sea sediments can be considered for the disposal of CO2.

Different methods have been proposed for history matching production of shale gas/oil wells which are drilled horizontally and usually hydraulically fractured with multiple stages. These methods are simulation, analytical models, and empirical equations. It has been well known that among the methods listed above, analytical models are more favorable in application to field data for two reasons. First, analytical solutions are faster than simulation, and second, they are more rigorous than empirical equations. Production behavior of horizontally drilled shale gas/oil wells has never been completely matched with the models which are described in this thesis. For shale gas wells, correction due to adsorption is explained with derived equations. The algorithm which is used for history matching and forecasting is explained in detail with a computer program as an implementation of it that is written in Excel's VBA. As an objective of this research, robust method is presented with a computer program which is applied to field data. The method presented in this thesis is applied to analyze the production performance of gas wells from Barnett, Woodford, and Fayetteville shales. It is shown that the method works well to understand reservoir description and predict future performance of shale gas wells. Moreover, synthetic shale oil well also was used to validate application of the method to oil wells. Given the huge unconventional resource potential and increasing energy demand in the world, the method described in this thesis will be the "game changing" technology to understand the reservoir properties and make future predictions in short period of time.

This thesis comprised patients with chronic rheumatic diseases. The studies aimed to elucidate food sensitivity by measuring mucosal inflammatory reactivity and thereby a possible link between the gut and joints. In all the studies, the mucosal path technique was used to evaluate the rectal mucosal response to rectal challenge with gluten and/or cow’s milk protein (CM). In some patients with primary Sjögren’s syndrome (pSS) and the genetic susceptibility genes HLA DQ2, mucosal reactivity measured with nitric oxide (NO) was found after rectal gluten challenge without detectable serum antibodies to gluten or transglutaminase. This gluten sensitivity was not linked to coeliac disease. After rectal CM challenge, a rectal mucosal inflammatory response measured with NO and myeloperoxidase (MPO) was detected in 38% of pSS patients, all of whom fulfilled the criteria for irritable bowel syndrome. In a questionnaire study of self-experienced adverse reactions to food, 27% of patients with rheumatoid arthritis (RA) reported intolerance to various foods and CM in particular. After rectal CM challenge performed in RA patients (n=27), strong mucosal reactivity to CM was observed in a few patients and a moderate increase in 23%. After gluten challenge, a moderate increase in mucosal reactivity was found in 35% of patients. No correlation to self-perceived intolerance and mucosal reactivity measured with NO and MPO was seen. Inflammation of the gut is a prominent feature of spondyloarthropathies (SpA). After rectal challenges with CM protein and gluten, an increase in rectal NO production was seen in 26% and 19% respectively (p&lt;0.001). An increase in the mucosal release of MPO as a sign of neutrophil activation was seen in the CM- and gluten-sensitive patients. NO production in SpA patients was more enhanced compared with RA and pSS patients and could contribute to the increased barrier permeability described in SpA patients.

Non-Aqueous Phase Liquids (NAPLs) include commonly occurring organic contaminants such as gasoline, diesel fuel and chlorinated solvents. When released to subsurface environments their spreading is a complex process of multi-component, multi-phase flow. This work has strived to develop new models and methods to describe the spreading of NAPLs in heterogeneous geological media. For two-phase systems, infiltration and immobilisation of NAPL in stochastically heterogeneous, water-saturated media were investigated. First, a methodology to continuously measure NAPL saturations in space and time in a two-dimensional experiment setup, using multiple-energy x-ray-attenuation techniques, was developed. Second, a set of experiments on NAPL infiltration in carefully designed structures of well-known stochastic heterogeneity were conducted. Three detailed data-sets were generated and the importance of heterogeneity for both flow and the immobilised NAPL architecture was demonstrated. Third, the laboratory experiments were modelled with a continuum- and Darcy’s-law-based multi-phase flow model. Different models for the capillary pressure (Pc) – fluid saturation (S) – relative permeability (kr) constitutive relations were compared and tested against experimental observations. A method to account for NAPL immobility in dead-end pore-spaces during drainage was introduced and the importance of accounting for hysteresis and NAPL entrapment in the constitutive relations was demonstrated. NAPL migration in three-phase, water-NAPL-air systems was also studied. Different constitutive relations used in modelling of three-phase flow were analysed and compared to existing laboratory data. To improve model performance, a new formulation for the saturation dependence of tortuosity was introduced and different scaling options for the Pc-S relations were investigated. Finally, a method to model the spreading of multi-constituent contaminants using a single-component multi-phase model was developed. With the method, the migration behaviour of individual constituents in a mixture, e.g. benzene in gasoline, could be studied, which was demonstrated in a modelling study of a gasoline spill in connection with a transport accident. / Flerfasföroreningar innefattar vanligt förekommande organiska vätskor som bensin, dieselolja och klorerade lösningsmedel. Spridningen av dessa föroreningar i mark är komplicerad och styrs av det samtidiga flödet av organisk vätska, vatten och markluft samt utbytet av komponenter (föroreningar) mellan de olika faserna. Detta arbete syftade till att utveckla nya metoder och modeller för att studera spridningen av flerfasföroreningar i mark: (i) En metodik utvecklades för att i laboratorium noggrant och kontinuerligt mäta hur en organisk vätska är rumsligt fördelad i en tvådimensionell experimentuppställning. Metoden baserades på röntgenutsläckning för olika energinivåer. (ii) Infiltration av organisk vätska i vattenmättade medier studerades för olika konfigurationer av geologisk heterogenitet. I experimentuppställningen packades olika sandmaterial noggrant för att konstruera en välkänd, stokastiskt heterogen struktur. Spridningsprocessen dokumenterades i tre detaljerade mätserier och heterogenitetens påverkan på flöde och kvarhållning av den organiska vätskan påvisades. (iii) Experimenten simulerades med en numerisk modell. Olika modeller prövades för att beskriva de grundläggande relationerna mellan kapillärtryck (Pc) vätskehalt (S) och relativ permeabilitet (kr) för detta tvåfassystem av vatten och organisk vätska. En relation infördes för att beskriva partiell orörlighet hos den organiska vätskan i porer vars halsar tillfälligt blockeras av vatten då mediet avvattnas. Vikten av att i de grundläggande relationerna ta hänsyn till hysteresis och kvarhållning av organisk fas visades. (iv) Olika Pc-S-kr relationer för trefassystem av vatten, organisk vätska och markluft testades mot befintliga experimentella data. En ny relation för hur slingrigheten (eng. tortuosity) beror av vätskehalten infördes i kr-S relationen och olika möjligheter för att skala Pc-S relationen analyserades. (v) En modelleringsmetodik utvecklades för att studera spridningen av flerkomponentsföroreningar. Med metoden kunde spridningsbeteendet hos enskilda, särskilt skadliga komponenter som t.ex. bensen särskiljas då ett bensinutsläpp i samband med en transportolycka simulerades.

Polymer networks are an important class of materials that are ubiquitously found in natural, biological, and man-made systems. The complex mesoscale structure of these soft materials has made it difficult for researchers to fully explore their properties. In this dissertation, we introduce a coarse-grained computational model for permanently cross-linked polymer networks than can properly capture common properties of these materials. We use this model to study several practical problems involving dry and solvated networks. Specifically, we analyze the permeability and diffusivity of polymer networks under mechanical deformations, we examine the release of encapsulated solutes from microgel capsules during volume transitions, and we explore the complex tribological behavior of elastomers. Our simulations reveal that the network transport properties are defined by the network porosity and by the degree of network anisotropy due to mechanical deformations. In particular, the permeability of mechanically deformed networks can be predicted based on the alignment of network filaments that is characterized by a second order orientation tensor. Moreover, our numerical calculations demonstrate that responsive microcapsules can be effectively utilized for steady and pulsatile release of encapsulated solutes. We show that swollen gel capsules allow steady, diffusive release of nanoparticles and polymer chains, whereas gel deswelling causes burst-like discharge of solutes driven by an outward flow of the solvent initially enclosed within a shrinking capsule. We further demonstrate that this hydrodynamic release can be regulated by introducing rigid microscopic rods in the capsule interior. We also probe the effects of velocity, temperature, and normal load on the sliding of elastomers on smooth and corrugated substrates. Our friction simulations predict a bell-shaped curve for the dependence of the friction coefficient on the sliding velocity. Our simulations also illustrate that at low sliding velocities, the friction decreases with an increase in the temperature. Overall, our findings improve the current understanding of the behavior of polymer networks in equilibrium and non-equilibrium conditions, which has important implications for synthesizing new drug delivery agents, designing tissue engineering systems, and developing novel methods for controlling the friction of elastomers.

Quattro diversi esperimenti sono stati eseguiti per investigare i fattori che influenzano la fermentazione ruminale delle diete altamente fermentescibili e per sviluppare un modello per studiare la permeabilità gastro-intestinale nei ruminanti. Nello studio 1, quattro ibridi di mais sono stati valutati per la digeribilità ruminale delle loro frazioni. I risultati suggeriscono che i genotipi e le fasi di maturità influenzano fortemente la digeribilità della sostanza secca e dell’amido nel rumine. Nello studio 2, i risultati della fermentazione in vitro di diversi zuccheri ha rivelato che il lattulosio può essere uno zucchero indicatore per studiare la permeabilità intestinale nei ruminanti, grazie alla sua bassa fermentescibilità ruminale. Nello studio 3, per la prima volta un modello di enteropatia indotta da indometacina è stato utilizzato per valutare nei ruminanti la permeabilità dell’intestino tenue attraverso il test del lattulosio. I risultati mostrano che il lattulosio è passato dall'intestino al sangue modificando alcuni parametri metabolici e dell'infiammazione. Nello studio 4, una acidosi acuta è stata indotta in pecore per testare la permeabilità gastro-intestinale con il test del lattulosio. I risultati hanno dimostrato che l'acidosi acuta compromette il funzionamento della barriera gastro-intestinale consentendo l'assorbimento e la traslocazione di LPS e altre sostanze nocive e incrementa l'infiammazione. / Four different experiments were performed for the better understanding of the factors that affect rumen fermentation of highly fermentable diets and to develop a model to study GI permeability in ruminants. In study 1, four corn hybrids recommended for corn silage were evaluated for ruminal starch digestibility of their grain fractions. Results suggest that the genotypes and maturity stages greatly influenced the DM and starch digestibility in rumen. In study 2, the results of the in vitro rumen fermentation of different naturally occurring and synthetic sugars revealed that lactulose can be a good probe sugar to study GI tract permeability in ruminants due to its low and slow fermentation rate in rumen. In study 3, for the first time an indomethacin-induced enteropathy model was used in ruminants to assess small intestinal permeability by the lactulose test. The results established that lactulose passed from the intestine to blood with perturbation of some metabolic parameters and inflammation. In study 4, acute acidosis was induced in sheep to test GI permeability during acidosis condition by lactulose test. The results demonstrated that acute acidosis impair the GI barrier function which allow absorption and translocation of LPS and other harmful substances and increase inflammation.