Hydraulic fracturing is an important method used to enhance the recovery of oil and gas from reservoirs, especially for low permeability formations. The distribution of pressure in fractures and fracture geometry are needed to design conventional and unconventional hydraulic fracturing operations, fracturing during water-flooding of petroleum reservoirs, shale gas, and injection/extraction operation in a geothermal reservoir. Designing a hydraulic fracturing job requires an understanding of fracture growth as a function of treatment parameters. There are various models used to approximately define the development of fracture geometry, which can be broadly classified into 2D and 3D categories. 2D models include, the Perkins-Kern-Nordgren (PKN) fracture model, and the Khristianovic-Geertsma-de. Klerk (KGD) fracture model, and the radial model. 3D models include fully 3D models and pseudo-three-dimensional (P-3D) models. The P-3D model is used in the oil industry due to its simplification of height growth at the wellbore and along the fracture length in multi-layered formations. In this research, the Perkins-Kern-Nordgren (PKN) fracture model is adopted to simulate hydraulic fracture propagation and recession, and the pressure changing history. Two different approaches to fluid leak-off are considered, which are the classical Carter's leak-off theory with a constant leak-off coefficient, and Pressure-dependent leak-off theory. Existence of poroelastic effect in the reservoir is also considered. By examining the impact of leak-off models and poroelastic effects on fracture geometry, the influence of fracturing fluid and rock properties, and the leak-off rate on the fracture geometry and fracturing pressure are described. A short and wide fracture will be created when we use the high viscosity fracturing fluid or the formation has low shear modulus. While, the fracture length, width, fracturing pressure, and the fracture closure time increase as the fluid leak-off coefficient is decreased. In addition, an algorithm is developed for the post-fracture pressure-transient analysis to calculate formation permeability. The impulse fracture pressure transient model is applied to calculate the formation permeability both for the radial flow and linear fracture flow assumption. Results show a good agreement between this study and published work.

Chronisch entzündliche Darmerkrankungen stellen eine Gruppe von chronischen, häufig in Schüben verlaufenden Erkrankungen mit rezidivierenden Entzündungen des Gastrointestinaltraktes dar. Es konnte gezeigt werden, dass eine gestörte Barrierefunktion einen wichtigen Schritt für die Pathogenese darstellt und dass das Zytokin Tumornekrosefaktor alpha (TNF) eine entscheidende Rolle dabei spielt. Die Rolle der kleinen GTPase RhoA bei der TNF-induzierten Barrieredysfunktion ist aufgrund der Komplexität der Signalwege nicht vollständig verstanden. Daher sollte der Einfluss von RhoA und der RhoA Effektorkinase PKN auf diese Prozesse in vitro mit Hilfe eines induzierbaren Expressionssystems untersucht werden, welches die kontrollierte Expression einer konstitutiv aktiven (KA) RhoA- und PKN-Mutante sowie einer dominant negativen (DN) PKN-Mutante ermöglichte. Die Induktion der KA RhoA Expression führte zu einer Störung der epithelialen Barriere. Eine simultane Interferon-gamma und TNF-Behandlung resultierte ebenfalls in einer gestörten Barrierefunktion, welche in KA RhoA Zellen weniger stark ausgeprägt war. Die TNF-Behandlung führte zu einer Aktivierung von PKN, weshalb dieses Protein ein Kandidat für die Vermittlung dieser Effekte darstellte. Inhibition von PKN mit Inhibitoren oder der Expression der DN Mutante führten zu einer Aggravierung der TNF-induzierten Barrieredysfunktion, welche durch eine Verringerung des transepithelialen elektrischen Widerstandes und eine erhöhte Ionenpermeabilität charakterisiert war. Diese Veränderungen wurden von einer Erhöhung des Myosin Leichtketten und NF-kappaB p65-Phosphorylierungsniveaus sowie von morphologischen Veränderungen begleitet. Im Gegensatz dazu konnten diese Veränderungen durch die Expression der KA PKN Variante abgeschwächt bzw. verhindert werden. Diese Ergebnisse liefern Hinweise auf eine potenzielle Rolle der RhoA Effektorkinase PKN bei der Modulation der TNF-induzierten Barrieredysfunktion in intestinalen Epithelzellen. / Inflammatory bowel diseases are relapsing systemic inflammatory diseases of the gastrointestinal tract associated with high morbidity and costs. A plethora of studies demonstrated that impaired intestinal barrier function is a key step in the pathogenesis of inflammatory bowel diseases and that the cytokine tumor necrosis factor alphpa (TNF) is of pivotal importance for this effect. Although the small GTPase RhoA has been implicated in the control of tight junction function, its role in TNF induced barrier dysfunction is not entirely understood due to the complexity of its downstream signaling pathways. Therefore, the contribution of RhoA and its effector kinase PKN on TNF induced barrier dysfunction was investigated in vitro. An inducible expression system that allowed the doxycyline controlled expression of a constitutively active (CA) RhoA and PKN mutant as well as a dominant negative (DN) PKN mutant was generated. Induction of CA RhoA expression led to an impaired epithelial barrier. Simultaneous Interferon-gamma and TNF treatment also resulted in barrier perturbation, but this defect was attenuated when CA RhoA was expressed. As treatment with TNF resulted in activation of the RhoA effector kinase PKN, this protein constitutes a candidate molecule for the mediation of these effects. Inhibition of PKN by inhibitory compounds as well as expression of a dominant negative PKN mutant aggravated TNF-induced barrier dysfunction, characterized by a decline in transepithelial electrical resistance and increased ion permeability. These alterations were accompanied by an increase in myosin light-chain and NF-kappaB p65 subunit phosphorylation level as well as morphological changes of the tight junctions. Conversely, expression of a CA PKN mutant attenuated or prevented these changes. These results provide support for a potential role of the RhoA effector kinase PKN in modulating the barrier disrupting effects of TNF in the intestinal epithelium.