La mise en évidence du rôle de la molécule SAMHD1 dans l’infection par le VIH-1 en tant que facteur de restriction a ouvert de nouvelles perspectives dans la compréhension de la pathogénicité du virus.En effet, il a été clairement démontré que dans les cellules myéloïdes comme les monocytes/macrophages et les cellules dendritiques ainsi que les lymphocytes T CD4+ quiescents, SAMHD1 jouait un rôle important dans la protection de ces cellules de l’infection. En revanche, le rôle de cette molécule dans l’infection des lymphocytes activés, qui sont souvent la cible préférentielle du virus, n’est pas élucidé.Nos résultats ont révélé l'existence d'une sous-population de lymphocytes T CD4+ mémoires exprimant de faibles niveaux de SAMHD1 (CD4+ CD45RO+ SAMHD1low), tandis que la grande majorité des lymphocytes expriment cette molécule à des niveaux plus élevés (94±0.7%). Nous montrons également que ces cellules sont hautement différenciées, qu’elles expriment en larges proportions le marqueur de cycle cellulaire Ki67 et qu’elles sont enrichies en cellules « T helper 17 » (Th17) dans le sang périphérique.De plus, la fréquence de la population CD4+ CD45RO+ SAMHD1low, est diminuée de manière significative chez les patients infectés par le VIH-1 par rapport aux sujets sains. De manière intéressante, nous montrons que dans les ganglions, les cellules T follicular helper (Tfh) expriment faiblement SAMHD1 et sont plus susceptibles à l’infection par le VIH-1 in vitro.L’ensemble de ces résultats suggère que les cellules SAMHD1 low représentent une cible préférentielle pour le virus et pourraient contribuer au réservoir viral.Les objectifs de ce projet sont:1. Déterminer si les cellules SAMHD1low contiennent plus de virus par comparaison aux cellules mémoires SAMHD1high et comparer les séquences virales isolées des cellules mémoires SAMHD1low et SAMHD1high.2. Caractérisation des cellules SAMHD1low au niveau moléculaire par une analyse transcriptomique qui permettra la mise en évidence de marqueurs membranaires. / We have previously reported the presence of memory CD4+ T cells that display low levels of SAMHD1 (SAMHD1low ) enriched in Th17 and Tfh cells. Here we investigated gene expression profile and the size and composition of HIV DNA population in SAMHD1 low cells.A total of 36 individuals on c-ART (median: 7y) with median CD4+ counts and nadir of 549 cells/ul and 210 cells/ul respectively, including 6 elite controllers (EC, CD4+: 900 cells/ul) and 8 healthy donors were studied. Blood memory CD4+ CD45RO+ SAMHD1low, CD45RO+ SAMHD1high and naive CD45RO- SAMHD1high cells were sorted. Cell associated HIV-1 DNA levels were quantified (HIV DNA Cell, Biocentric) and ultra-deep-sequencing (UDS, 454/Roche) of partial env (C2/V3) HIV-1 DNA was performed. Gene expression profile on sorted cells was deternined with RNA-Sequencing (Illumina RNASeq technology). Levels of HIV-1 DNA were significantly higher in memory SAMHD1low cells compared to SAMHD1high cells (4.5 [3.1-6.2] vs 3.8 [2.9-5.7] log/10 6 cells, respectively, p=0.02) among c-ART individuals, while naïve CD45RO- SAMHD1high showed lower levels (3.1 [1.6-4.4]). EC exhibited low HIV-1 DNA level in both SAMHD1low and SAMHD1high (1.6 and 2.3 log/10 6 cells respectively p>0.05). Naïve CD45RO - SAMHD1 high cells from EC showed lower DNA compared to naïve cells from c-ART pts (1.6 and 3.1 log/10 6 cells, respectively, p=0.01). Phylogenetic analyses revealed well-segregated HIV-DNA populations between subsets with significant compartmentalization between SAMHD1low and SAMHD1high cells in all but 2 participants (p<0.001) and limited viral exchange. Moreover SAMHD1low cells exhibited a distinct gene profile as compared to SAMHD1high allowing thus further characterisation of these cells.This pilot study revealed distinct HIV DNA populations in size and composition associated with unique genes profile in memory SAMHD1low cells. We show that memory SAMHD1low cells exhibit distinct genes profile which segregates them from the SAMHD1 high counterpart, and contain the highest level of HIV-1 DNA. We reveal distinct/well-segregated HIV-1 DNA populations in both subsets, suggesting minimal viral exchange.

Orientador: Denis José Schiozer / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica e Instituto de Geociências / Made available in DSpace on 2018-08-20T23:37:27Z (GMT). No. of bitstreams: 1 HohendorffFilho_JoaoCarlosvon_M.pdf: 5040063 bytes, checksum: 8a1057c3970e37d062f9eb5dca143421 (MD5) Previous issue date: 2012 / Resumo: Várias metodologias de acoplamento entre reservatórios e sistemas de produção têm sido aplicadas na indústria de petróleo nos últimos anos devido à necessidade de modelar adequadamente projetos de produção de petróleo cada vez mais complexos, que envolvem a solução integrada dos modelos que representam o escoamento de fluidos desde o reservatório até a superfície. Estas metodologias são utilizadas para fazer a previsão da produção de múltiplos reservatórios, compartilhando plataformas de produção com capacidades de produção e injeção limitadas gerenciadas por sistemas de produção complexos. Elas podem ser agrupadas em dois tipos básicos: metodologias de acoplamento implícito e explícito. A metodologia explícita é uma possível escolha para integrar simulações porque permite acoplar simuladores distintos para modelar o sistema com um todo adequadamente e também fornecer flexibilidade no estudo de alternativas de gerenciamento de poços. Esta metodologia, contudo, deve ser testada para verificar a qualidade dos resultados e eficiência. Desta forma, um estudo de validação da metodologia de acoplamento explícita é apresentado neste trabalho onde o sistema de produção é testado em condições operacionais comuns durante a produção e injeção de fluidos, verificando vantagens e limitações da metodologia explícita. Alguns métodos para o melhoramento da resposta explícita são propostos e avaliados. Um exemplo de aplicação mostra o ganho na flexibilidade de priorização de poços no gerenciamento de grupo obtido pelo uso de uma metodologia externa ao simulador de reservatórios. O acoplamento explícito, como implementado, mesmo com alguns problemas relacionados a instabilidade da solução numérica em situações específicas, apresentou resultados satisfatórios para a integração entre os simuladores, honrando as restrições operacionais fixadas nos casos de avaliação. Algumas análises em relação ao tempo total de simulação acoplada são apresentadas, mostrando uma não dependência do tamanho do problema em relação ao tempo total gasto / Abstract: Various methodologies to model the coupling of reservoirs and production systems have been applied in the oil industry in recent years due to the need to model properly the integrated solution of models that represent the flow of fluids through the reservoir to the surface. These methodologies are used to forecast production of multiple reservoirs, sharing production facilities with limited capacities ruled by complex systems. They can be grouped into two basic types: implicit and explicit coupling methodologies. Explicit methodology can be an efficient choice to integrate simulations because it allows coupling adequate simulators to model the whole system and also to add flexibility to study well management alternatives. A validation study of explicit coupling methodology is presented in this work where the production system is tested on common operating conditions during production and injection of fluids, verifying benefits and limitations of the methodology. Some methods for improving the explicit response are proposed and evaluated. An example of application verifies the gain of flexibility in well prioritization by the group management obtained by use of an external methodology for reservoir simulator. The explicit coupling, as implemented, even with some problems related to instability of numerical solution in specific situations, has shown a satisfactory result for the integration between the simulators, honoring operating constraints. Some analyses about elapsed time of coupling simulation are shown / Mestrado / Reservatórios e Gestão / Mestre em Ciências e Engenharia de Petróleo

This study developed new concepts and interpretative methods for mapping reservoir heterogeneity and connectivity of a fault controlled Wilcox clastic reservoir in Texas, USA. The application of high-resolution seismic enhancement in this study allows for better delineation of subsurface geologic features, detailed mapping of reservoir heterogeneities and more accurate identification of depositional, structural, and stratigraphic characteristics that control reservoir connectivity and fluid flow. Seismic enhancement in this study pertains to amplitude preserving neural network implementation of the Volterra integral equation of the first kind from a plane-wave solution of poro-viscoelasticity (Sun, et al., 2003). This enhancement amounts to an advanced spiked deconvolution of post-stack seismic data that broadened the dominant seismic frequency from 16Hz for the conventional seismic to 65Hz for the enhanced seismic. Bed resolution is improved from 175ft to 45ft and fault offset resolution is improved from 80ft to 20ft. High-resolution seismic interpretation was validated through synthetic seismograms, stratigraphic surface comparisons, and most importantly using a comprehensive model-based knowledge of regional tectonics and depositional environments. Stratigraphic features that were not resolvable in conventional seismic data can now be interpreted using the enhanced seismic data. An Upper Wilcox reservoir was identified as a transgressive sheet sand overlaying a progradational deltaic seismic facies. An Upper Middle Wilcox reservoir was identified as a probable lobate gravity flow, and a Middle Wilcox reservoir was identified as a transgressive sheet sand with over and underlying progradational deltaic seismic facies. Geobody extraction from seismic inversion volumes delineates reservoir compartments and flow units. Reservoir connectivity analysis performed on the Middle Wilcox reservoir determined the probable drainage area for a producing well by comparing estimates of compartmentalized hydrocarbon volumes with production information. The methodology developed could help extract connected geobodies defined by sand, porosity, permeability, and hydrocarbon indicators, to map in detail the internal structure of produced reservoir and to locate new development prospects. Enhanced seismic may thus enable us to find bypassed hydrocarbons and to provide better methods for improving recovery in the studied and other mature fields.

The Amistad Reservoir in southern Val Verde County, Texas will impound a considerable amount of surface water in a semi-arid region in which natural surface water is scarce. Construction of the dam began in 1963 and the reservoir began to fill in the summer of 1968. This large impoundment could have a considerable ecological impact on the area. The purpose of this research was to study the ecological distribution and zoogeographic affinities of the herpetofauna and to establish an ecological baseline against which any future changes could be measured.

History matching is a process wherein changes are made to an initial geologic model of a reservoir, so that the predicted reservoir performance matches with the known production history. Changes are made to the model parameters which include rock and fluid parameters (viscosity, compressibility, relative permeability, etc.) or properties within the geologic model. Assisted History Matching (AHM) provides an algorithmic framework to minimize the mismatch in simulation, and aids in accelerating this process. The changes made by AHM techniques, however, cannot ensure a geologically consistent reservoir model. In fact, the performance of these techniques depends on the initial starting model. In order to understand the impact of the initial model, this project explored the performance of the AHM approach using a specific field case, but working with multiple distinct geologic scenarios. This project involved an integrated seismic to simulation study, wherein I interpreted the seismic data, assembled the geological information, and performed petrophysical log evaluation along with well test data calibration. The ensemble of static models obtained was carried through the AHM methodology. I used sensitivity analysis to determine the most important dynamic parameters that affect the history match. These parameters govern the large scale changes in the reservoir description and are optimized using the Evolutionary Strategy Algorithm. Finally, the streamline based techniques were used for local modifications to match the water cut well by well. The following general conclusions were drawn from this study- a) The use of multiple simple geologic models is extremely useful in screening possible geologic scenarios and especially for discarding unreasonable alternative models. This was especially true for the large scale architecture of the reservoir. b) The AHM methodology was very effective in exploring a large number of parameters, running the simulation cases, and generating the calibrated reservoir models. The calibration step consistently worked better if the models had more spatial detail, instead of the simple models used for screening. c) The AHM methodology implemented a sequence of pressure and water cut history matching. An examination of specific models indicated that a better geologic description minimized the conflict between these two match criteria.

A significant body of work has demonstrated both the promise and difficulty of quantifying uncertainty in reservoir simulation forecasts. It is generally accepted that accurate and complete quantification of uncertainty should lead to better decision making and greater profitability. Many of the techniques presented in past work attempt to quantify uncertainty without sampling the full parameter space, saving on the number of simulation runs, but inherently limiting and biasing the uncertainty quantification in the resulting forecasts. In addition, past work generally has looked at uncertainty in synthetic models and does not address the practical issues of quantifying uncertainty in an actual field. Both of these issues must be addressed in order to rigorously quantify uncertainty in practice. In this study a new approach to reservoir simulation is taken whereby the traditional one-time simulation study is replaced with a new continuous process potentially spanning the life of the reservoir. In this process, reservoir models are generated and run 24 hours a day, seven days a week, allowing many more runs than previously possible and yielding a more thorough exploration of possible reservoir descriptions. In turn, more runs enabled better estimates of uncertainty in resulting forecasts. A new technology to allow this process to run continuously with little human interaction is real-time production and pressure data, which can be automatically integrated into runs. Two tests of this continuous simulation process were conducted. The first test was conducted on the Production with Uncertainty Quantification (PUNQ) synthetic reservoir. Comparison of our results with previous studies shows that the continuous approach gives consistent and reasonable estimates of uncertainty. The second study was conducted in real time on a live field. This study demonstrates the continuous simulation process and shows that it is feasible and practical for real world applications.

Reservoir models are generally constructed from seismic, well logs and other related datasets using inversion methods and geostatistics. It has already been recognized by the geoscientists that such a process is prone to non-uniqueness. Practical methods for estimation of uncertainty still remain elusive. In my dissertation, I propose two new methods to estimate uncertainty in reservoir models from seismic, well logs and well production data. The first part of my research is aimed at estimating reservoir impedance models and their uncertainties from seismic data and well logs. This constitutes an inverse problem, and we recognize that multiple models can fit the measurements. A deterministic inversion based on minimization of the error between the observation and forward modeling only provides one of the best-fit models, which is usually band-limited. A complete solution should include both models and their uncertainties, which requires drawing samples from the posterior distribution. A global optimization method called very fast simulated annealing (VFSA) is commonly used to approximate posterior distribution with fast convergence. Here I address some of the limitations of VFSA by developing a new stochastic inference method, named Greedy Annealed Importance Sampling (GAIS). GAIS combines VFSA with greedy importance sampling (GIS), which uses a greedy search in the important regions located by VFSA to attain fast convergence and provide unbiased estimation. I demonstrate the performance of GAIS on post- and pre-stack data from real fields to estimate impedance models. The results indicate that GAIS can estimate both the expectation value and the uncertainties more accurately than using VFSA alone. Furthermore, principal component analysis (PCA) as an efficient parameterization method is employed together with GAIS to improve lateral continuity by simultaneous inversion of all traces. The second part of my research involves estimation of reservoir permeability models and their uncertainties using quantitative joint inversion of dynamic measurements, including synthetic production data and time-lapse seismic related data. Impacts from different objective functions or different data sets on the model uncertainty and model predictability are investigated as well. The results demonstrate that joint inversion of production data and time-lapse seismic related data (water saturation maps here) reduces model uncertainty, improves model predictability and shows superior performance than inversion using one type of data alone. / text

Thesis (Ph.D.)--University of Tulsa, 1993. / Bibliography: leaves 179-186.

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Kamy Sepehrnoori. Vita. Includes bibliographical references.

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