Adherens junctions are cadherin-dependent structures that mediate intercellular signaling and structural integrity of the endothelial barrier. Formins are a highly conserved family of cytoskeletal remodeling proteins whose activity has been implicated in regulating adherens junction formation in other cell-types. Therefore, we tested the hypothesis that formin activity is essential for adherens junction assembly in endothelial cells. A small-molecule formin inhibitor (smiFH2) was used to determine the effect of formin inhibition on junction formation using an in vitro vascular permeability assay. We determined that smiFH2 treatment caused a dose-dependent inhibition of junction formation. We used siRNAs to knockdown expression of the seven formins shown to be expressed in TIME cells and determined that individual knockdown of FHOD1, FHOD3 and Dia1 significantly increased the permeability of the endothelial monolayer. Interestingly, FMNL2 knockdown actually potentiated barrier function. Knockdown of the remaining formins had little or no effect on junction formation. Knockdown of FHOD3 had the greatest inhibitory effect on junction assembly; VE-cadherin protein levels were decreased in FHOD3-depleted cells. The FHOD3 knockdown cells were also elongated in comparison to controls and formed thin linear adherens junctions and few focal adherens junctions. In contrast, the morphology of FMNL2-depleted cells did not appear obviously different from controls. In conclusion, our results suggest that multiple formins play diverse roles in adherens junction formation and maintenance in endothelial cells.

Habitat modification alters species' capacities to track shifting climatic conditions. Broad-scale analyses that explore demographical responses to on-going climate change tend to neglect the influence of the underlying landscape pattern. However, many landscapes are fragmented by human activities, which might make dispersal for many species more challenging. Determining the extent to which landscape factors affect broad-scale distributional patterns has implications for our ability to predict realistic climate change impacts on species. Here, we constructed species-specific measurements of landscape permeability for 96 butterfly species in southern Ontario to test whether this landscape characteristic affected species' distributions at macroecological scales. We used multiple logistic regression models to test for the effects of permeability and its interaction with temperature on butterfly species presence/absence. We found that 48% of butterfly species responded to landscape permeability alone or in interaction with temperature. In general, the effect was positive (87%) and species were more likely to be present with increasing landscape permeability. For 61% of the species that responded to broad-scale landscape permeability, the interaction of temperature with permeability was statistically significant. In warm areas, species were more likely to be present if landscape permeability was high. Landscape permeability explained 3-43% of residual variability in species' presences after accounting for temperature. Finally, we show how fine-scale permeability measurements can be combined with large-scale patterns of diversity to inform conservation efforts. Landscape permeability can affect species' distributions at broad-scales and understanding factors that potentially influence species' dispersal can improve predictions for how species respond to changing climatic conditions.

Orientador: Rosângela Barros Zanoni Lopes Moreno / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica e Instituto de Geociências / Made available in DSpace on 2018-08-22T09:00:58Z (GMT). No. of bitstreams: 1 Lopes_FelipeRobles_M.pdf: 3706160 bytes, checksum: 5656fb6101eaefe1ce42e6acd4bcca9d (MD5) Previous issue date: 2013 / Resumo: A invasão de fluidos de perfuração e suas consequências na produção de petróleo são bem conhecidas e intensivamente discutidas por especialistas. Além disso, a comunidade científica tem buscado o entendimento dos mecanismos de invasão e do retorno de permeabilidade. Este estudo estende investigações anteriores sobre análise de dano e inclui as etapas de invasão de fluido de perfuração e de fluxo reverso de óleo. Foram realizados testes de invasão de fluidos base-água, soluções de goma xantana e de poliacrilamida, à pressão constante, em amostras saturadas com óleo e água conata. Usando um porta-testemunho especial, perfis de saturação e de pressão foram monitorados durante a invasão e o fluxo reverso, permitindo a observação das características do processo de invasão e de remoção do dano de forma dinâmica. A condição de saturação da amostra antes da invasão de polímero, óleo e água conata, permitiu melhorar a representatividade de um reservatório de petróleo. O monitoramento da pressão ao longo da direção de escoamento e varreduras de Raios-X combinados com o balanço de massa de fluidos injetados e produzidos permitiu observar o avanço do fluido invasor. Durante o fluxo reverso foi possível acompanhar dinamicamente a mudança de permeabilidade da região invadida. As principais contribuições deste estudo referem-se à análise do retorno de permeabilidade devido à produção de óleo em uma região danificada pela invasão do fluido de perfuração, bem como a influência da presença de água conata nestes processos / Abstract: Invasion of drilling fluids and their effects on oil production are well known and have been extensively discussed by experts. Furthermore, the scientific community has invested a lot of effort into understanding the mechanisms of invasion and permeability restoration. This study extends previous investigations and includes both invasion and back flow evaluation conditions. Test sample, initially at connate water condition, were submitted to constant pressure displacement. Using a special core holder, saturation and pressure profiles were monitored during overbalance pressure invasion and oil back flow. Monitored data has allowed observing the formation damage characteristics as well as cleaning dynamics. In this work, polymer injection into the sample at residual water saturation has improved the reservoir representation. The pressures data, from the taps along the core, X-Ray data and also the mass balance allow the author to follow the invasive fluid going through the core. Additional insights about dynamic mechanisms were also discussed based on a large quantity of monitored data. During the back flow was possible to dynamically monitor the change of permeability of the invaded region. The main contributions of this study are related to the analysis of the permeability restoration due to oil natural cleanup of the region damage by drill in fluid. The influence of connate water in this process was also important / Mestrado / Reservatórios e Gestão / Mestre em Ciências e Engenharia de Petróleo

>Magister Scientiae - MSc / This contribution engages in the evaluation of offshore sandstone reservoirs of the Central Bredasdorp basin, Block 9, South Africa using primarily petrophysical procedures. Four wells were selected for the basis of this study (F-AH1, F-AH2, F-AH4, and F-AR2) and were drilled in two known gas fields namely F-AH and F-AR. The primary objective of this thesis was to evaluate the potential of identified Cretaceous sandstone reservoirs through the use and comparison of conventional core, special core analysis, wire-line log and production data. A total of 30 sandstone reservoirs were identified using primarily gamma-ray log baselines coupled with neutron-density crossovers. Eleven lithofacies were recognised from core samples. The pore reduction factor was calculated, and corrected for overburden conditions. Observing core porosity distribution for all wells, well F-AH4 displayed the highest recorded porosity, whereas well F-AH1 measured the lowest recorded porosity. Low porosity values have been attributed to mud and silt lamination influence as well as calcite overgrowths. The core permeability distribution over all the studied wells ranged between 0.001 mD and 2767 mD. Oil, water, and gas, were recorded within cored sections of the wells. Average oil saturations of 3 %, 1.1 %, and 0.2 % were discovered in wells F-AH1, F-AH2, and F-AH4. Wells F-AH1 to F-AR2 each had average gas saturations of 61 %, 57 %, 27 %, and 56 % respectively; average core water saturations of 36 %, 42 %, 27 %, and 44 % were recorded per well.

Este trabalho tem por objetivo estudar a molhabilidade e a permeabilidade para quatro espécies de madeiras tropicais (Pinus elliottii, Araucaria angustifolia, Eucalyptus grandis e Eucalyptus citriodora). A molhabilidade é um parâmetro importante para a caracterização de diferentes espécies de madeira e, portanto, depende de fatores como o estado de limpeza da superfície da madeira, orientação das fibras, tipo de amostra (alburno ou cerne), secagem, tratamentos térmicos e químicos, rugosidade superficial, etc. Primeiramente, investigamos a molhabilidade para as quatro espécies tropicais por medida de ângulo de contato aparente para diferentes solventes na superfície da madeira As amostras foram tratadas termicamente no intervalo 100 200º C, por 8h e foi utilizado o método da gota séssil e um goniômeto. Os valores dos ângulos de contato foram maiores para as amostras submetidas aos tratamentos térmicos, indicando um aumento no caráter hidrofóbico da madeira. A técnica de ângulo de contato não foi eficiente para tratamentos térmicos superiores a 200º C, devido a sua degradação. No experimento de permeabilidade foi utilizado um fluxo de ar através das amostras com poros fechados e abertos. Foi verificado um acréscimo de 82 % na vazão para as situações de poros abertos no Eucalyptus citriodora. Nossos resultados permitem detectar mudanças consideráveis na molhabilidade e permeabilidade da madeira, sendo informações valiosas para a conservação e utilização destas madeiras. / This work aims to study wettability and permeability for tropical wood species (Pinus elliotti, Araucaria angustifolia, Eucalyptus grandis and Eucalyptus citriodora).The adhesive wettability is an important parameter for characterizing different wood species and depends on factors such as cleaning state of the wood surface, orientation of the wood fibers, type of sample (sapwood or heartwood), drying, thermal and chemical treatments, surface roughness, etc. First, we investigated the wettability of the four tropical wood species by measuring the apparent contact angles of different solvents on the wood surfaces. The samples were heat treated from 100 to 200 °C for 8 h, and the contact angles measured by the sessile drop method with a home-made goniometer. For samples heat-treated below 200 °C, higher values of contact angles were obtained, indicating a hydrophobic character for thermal treated woods. After this temperature, the wood degradation took place. For permeability experiments, a flow of air was used for wood samples with closed and open pores. An increase of 82% in flow was verified for open pores woods such as Eucalyptus citriodora. Our results allowed us to detect considerable changes on wood wettability and permeability and that are powerful information for conservation and use of these woods.

AN ABSTRACT OF THE DISSERTATION OFSUMAN SAURABH, for the Doctor of Philosophy degree in Engineering Science, presented on August 30, 2019, at Southern Illinois University Carbondale.TITLE: GEOMECHANICAL STATE OF ROCKS WITH DEPLETION IN UNCONVENTIONAL COALBED METHANE RESERVOIRSMAJOR PROFESSOR: Dr. Satya HarpalaniOne of the major reservoir types in the class of unconventional reservoirs is coalbed methane. Researchers have treated these reservoirs as isotropic when modeling stress and permeability, that is, mechanical properties in all directions are same. Furthermore, coal is a highly sorptive and stress- sensitive rock. The focus of this dissertation is to characterize the geomechanical aspects of these reservoirs, strain, stresses, effective stress and, using the information, establish the dynamic flow/permeability behavior with continued depletion. Several aspects of the study presented in this dissertation can be easily extended to shale gas reservoirs. The study started with mechanical characterization and measurement of anisotropy using experimental and modeling work, and evaluation of how the sorptive nature of coal can affect the anisotropy. An attempt was also made to characterize the variation in anisotropy with depletion. The results revealed that the coals tested were orthotropic in nature, but could be approximated as transversely isotropic, that is, the mechanical properties were isotropic in the horizontal plane, but significantly different in vertical direction. Mechanical characterization of coal was followed by flow modeling. Stress data was used to characterize the changes in permeability with depletion. This was achieved by plotting stress path followed by coal during depletion. The model developed was used to successfully predict the permeability variation in coal with depletion for elastic deformations. As expected, the developed model failed to predict the permeability variation resulting from inelastic deformation given that it was based on elastic constitutive equations. Hence, the next logical step was to develop a generalized permeability model, which would be valid for both elastic and inelastic deformations. Investigation of the causes of coal failure due to anisotropic stress redistribution during depletion was also carried out as a part of this study. It was found that highly sorptive rocks experience severe loss in horizontal stresses with depletion and, if their mechanical strength is not adequate to support the anisotropic stress redistribution, rock failure can result. In order to develop a generalized permeability model based on stress data, stress paths for three different coal types were established and the corresponding changes in permeability were studied. Stress path plotted in an octahedral mean stress versus octahedral shear stress plane provided a signal for changes in the permeability for both elastic as well as inelastic deformations. This signal was used to develop a mechanistic model for permeability modeling, based on stress redistribution in rocks during depletion. The model was able to successfully predict the permeability variation for all three coal types. Finally, since coal is highly stress- sensitive, changes in effective stresses were found to be the dictating factor for deformations, changes in permeability and possible failure with depletion. Hence, the next step was to develop an effective stress law for sorptive and transversely isotropic rocks. For development of an effective stress law for stress sensitive, transversely isotropic rocks, previously established constitutive equations were used to formulate a new analytical model. The model was then used to study changes in the variation of Biot’s coefficient of these rocks. It was found that Biot’s coefficient, typically less than one, can take values larger than one for these rocks, and their values also change with depletion. The study provides a methodology which can be used to estimate the Biot’s coefficient of any rock. As a final step, preliminary work was carried out on the problem of under-performing coal reservoirs in the San Juan basin, where coal is extremely tight with very low permeability. An extension of the work presented in this dissertation is to use the geomechanical characterization techniques to unlock these reservoirs and improve their performance. The experimental data collected during this preliminary study is included in the last chapter of the dissertation.

The concrete is not one hundred percent impermeable since the water that remains inside it causes its corrosion, in the case of reinforced concrete, exposed in an area of marine atmosphere, the sea salt mostly present in large particles of the marine spray, produce the reduction of the alkalinity of the concrete causing a rapid corrosion of the steel. There are buildings built in this marine area that have been designed without durability criteria, in which the use of pozzolanic materials is considered, for example, to fill the pores of the cement matrix and thus guarantee its impermeability. In the present study, the effect of clay brick powder (PLA) as a replacement for cement in concrete manufacturing is addressed, evaluating different characteristics of its components. The results indicate that pozzolanic activity and compressive strength increase, slump, voids content and the coefficient of permeability to water decreases.

Mining is an important industry that plays a significant role in the development of human civilization and economies. However, the underground mining process produces a large volume of mine wastes (e.g., tailings) as well as creates large voids that require filling, typically with an engineering backfill material. Filling the voids with mine waste materials provides an environmental-friendly way of disposing mining waste. It is also an effective way of increasing ore recovery and improving the safety of miners. One of the best techniques of mine backfill is called cemented paste backfill (CPB), which is typically a mixture of tailings, binder and water. The most common binder used in the preparation of CPB is Portland cement (PC). PC is not only a costly binder, but its production is highly energy-intensive and also generates a large amount of CO2. The cement consumption can represent up to 75% of the cost of CPB. These above-mentioned factors have compelled mining companies to seek for cement alternatives that enhance the engineering properties of the CPB, decrease the cement content and reduce the carbon footprint of the mining industry. Sodium silicate is the most recent chemical additive that is proposed to reduce the binder content in CPB. Sodium silicate is an alkaline solution that is used to activate a pozzolanic material, such as cement, slag and Fly ash. However, the effect of sodium silicate on the strength and key environmental properties (permeability or saturated hydraulic conductivity, reactivity) of CPB is not well understood. The objective of this thesis is to investigate the possibility of using sodium silicate as an activator in cemented paste backfill and obtain an improvement in the aforementioned engineering properties of CPB. In order to determine the effect of the sodium silicate on backfill properties, some CPB testing methods were developed to fulfill the objectives of this research. Thus, the evolution of hydraulic, mechanical and microstructural properties of CPB samples containing sodium silicate (SS-CPB) have been tested or monitored at different curing ages (1, 3, 7, 28 and 90 days) and different CPB mixtures as well. The results of these studies show that activating CPB with sodium silicate develop CPB strength faster than CPB samples without sodium silicate. In addition, hydraulic conductivity and reactivity results show a positive change in samples containing sodium silicate compared to free sodium silicate CPB samples. Indeed, this activation leads to decreasing permeability and reactivity due to the formation of cement hydration products and acceleration of the binder hydration process. Moreover, binder type and content in the presence of sodium silicate as an alkali activator in the CPB play a significant role in lowering hydraulic conductivity and reactivity of CPB.

>Magister Scientiae - MSc / The thesis aims to determine the depositional environments, rock types and petrophysical characteristics of the reservoirs in Wells E-S3, E-S5 and F-AH4 of Area X in the Bredasdorp Basin, offshore South Africa. The three wells were studied using methods including core description, petrophysical analysis, seismic facies and multivariate statistics in order to evaluate their reservoir potential. The thesis includes digital wireline log signatures, 2D seismic data, well data and core analysis from selected depths. Based on core description, five lithofacies were identified as claystone (HM1), fine to coarse grained sandstone (HM2), very fine to medium grained sandstone (HM3), fine to medium grained sandstone (HM4) and conglomerate (HM5). Deltaic and shallow marine depositional environments were also interpreted from the core description based on the sedimentary structures and ichnofossils. The results obtained from the petrophysical analysis indicate that the sandstone reservoirs show a relatively fair to good porosity (range 13-20 %), water saturation (range 17-45 %) and a predicted permeability (range 4- 108 mD) for Wells E-S3, E-S5 andF-AH4. The seismic facies model of the study area shows five seismic facies described as parallel, variable amplitude variable continuity, semi-continuous high amplitude, divergent variable amplitude and chaotic seismic facies as well as a probable shallow marine, deltaic and submarine fan depositional system. Linking lithofacies to seismic facies maps helped to understand and predict the distribution and quality of reservoir packages in the studied wells. Multivariate statistical methods of factor, discriminant and cluster analysis were used. For Wells E-S3, E-S5 and F-AH4, two factors were derived from the wireline log data reflecting oil and non- oil bearing depths. Cluster analysis delineated oil and non-oil bearing groups with similar wireline properties. This thesis demonstrates that the approach taken is useful because petrophysical analysis, seismic facies and multivariate statistics has provided useful information on reservoir quality such as net to gross, depths of hydrocarbon saturation and depositional environment.

<div>Neurotherapeutics are an essential drug class that is often forgotten or neglected due to the difficulties associated with pharmaceutical development and approval. These compounds face high rates of attrition in clinical trials and late stage development predominantly due to the restrictiveness of the blood brain barrier (BBB). The inherent role of the BBB is to protect and maintain the homeostatic environment around the neuronal cells in the brain parenchyma. This is accomplished by the BBB posing not only as a physical barrier through its restrictive tight junctions that prevent paracellular permeation, but also through the high expression levels of efflux transporters and drug metabolizing enzymes that prevent transcellular permeation of potential drug compounds. In attempting to deliver compounds to the brain the intended outcome is often over-shot to the point of causing neurotoxic implications. One way to mitigate the difficulties associated with drug delivery to the brain and early evaluation of potential toxic compounds is to develop in vitro cell-based models that mimic the in vivo BBB and neurovascular unit (NVU). The mainstays of the BBB phenotype are presented in the brain microvessel endothelial cells (BMECs) and are regulated and influenced by the close contacts of supporting cells of the NVU such as astrocytes, pericytes, and neurons. An in vitro model that can mimic the close contacts between these four cell types and is capable of being implemented in pharmaceutical development for BBB permeability and neuroactivity screening could lead to better selection of hit and lead candidates, and ultimately reduce the attrition rates of neurotherapeutics.</div><div>Direct contact coculture and triculture models have been developed in our laboratory that mimic the in vivo cell-cell contacts between the different cell types of the NVU and provide increased barrier properties in comparison to other models utilizing indirect contact between cell types. Early development and optimization of these models was accomplished using the human cerebral endothelial cell line hCMEC/D3. Although this cell line proved useful in early validation stages, it was decided that a different endothelial cell source would be sought out. Work was done using iPSC derived endothelial cells (iCell® endothelial cells) and an alternative immortalized human brain endothelial cell line (HBEC-5i). Both cell lines proved to be amenable to the direct contact coculture and triculture models, with the iCell® models showing greater barrier properties in comparison to those using the HBEC-5i cell line. However, drawbacks of the iCell® model were observed in extending culturing of the cells causing the cells to “roll” to the middle of the filter and proving to be cost prohibitive for extensive optimization. Ultimately, the HBEC-5i cell line was chosen for continued development and optimization due to its immortalized origin and potential for replacing the hCMEC/D3 cell line in the direct contact models.</div><div>Optimization of the direct contact triculture using the HBEC-5i cell line was required as all of the previous development was performed using the hCMEC/D3 cells. Typically, optimization of in vitro systems is performed in a one factor at a time manner or not at all. Given the large number of factors that can influence the outcome of this model, a design of experiments (DOE) based optimization approach was taken. DOEs are traditionally used in process optimization of non-biologically based systems; however, the production of the direct contact triculture is a process that could greatly benefit from extensive optimization. The seeding densities of all three cell types used in the triculture (astrocytes, pericytes, and HBEC-5i), the extracellular matrix used, and the length of culture time post endothelial cell plating were the factors chosen for the optimization process given the observations made during early development of the model. The conditions were optimized for barrier tightness by measuring the permeability of a 4 kD dextran as a paracellular marker because the model would have limited utility without adequate tight junction formation. Based on the results of this work, optimized conditions were determined in a significantly reduced amount of time as compared to traditionally used cell model optimization methods and an in vitro BBB screening tool that mimics the physiology of the NVU was developed. Given the outcomes of these studies it can be seen that a DOE optimization approach should be considered for development of biologically based systems to understand interactions between key system factors and to reduce the time to develop these necessary systems.</div><div>BBB permeability is not the only factor that slows development of neurotherapeutics. The intent of many of these compounds is to elicit an effect on the neuronal environment; however, permeability and neuroactivity are often evaluated separately even though they are inherently linked in vivo. Further enhancement of the optimized direct contact triculture was done to develop a screening tool that could assess neuroactivity of a compound as it is related to its brain permeability. The in vitro NVU model was developed by adding human neurons to the basolateral chamber of the direct contact triculture so permeating compounds would accumulate in the receiver chamber and their neuronal effects could be measured. During development of this model it was seen that the addition of neurons both increases tightness of the apical BBB model, but also increases viability of the neurons themselves. This is likely due to the facilitation of cross-talk between the four cell types of the NVU due to the proximity of the cells in the model system. The BBB permeability linked neuroactivity of marker compounds was measured by neuronal viability and neurite outgrowth in response to compound accumulation over the neurons during the course of BBB permeation. The results of this assay showed that the model is capable of being used to assess both BBB permeability and the subsequent neuroactivity of a given compound, and that the inclusion of additional cell types from the NVU further increases the physiological relevancy of the model. This work shows that the NVU model is an enhancement of the direct contact triculture model and can be easily implemented in the early development stages of neurotherapeutic compounds. Ultimately, this model has the potential to increase the number of brain targeting compounds by facilitating early, predictive assessment and rank ordering of large compound libraries for continued development. </div><div><br></div>