L’adhésine impliquée dans l’adhérence diffuse (AIDA-I) est une adhésine bactérienne présente chez certaines souches d’Escherichia coli qui, associée aux toxines Stx2e ou STb, contribue à l’apparition de la maladie de l’œdème ou de la diarrhée post-sevrage chez les porcelets. AIDA-I est un autotransporteur qui confère des capacités d’autoaggrégation, de formation de biofilms et d’adhésion. L’objectif principal du projet de recherche consistait en la recherche de récepteur(s) potentiel(s) d’AIDA-I. Les bactéries pathogènes adhèrent aux cellules-cibles soit en liant directement des molécules à la surface cellulaire ou en utilisant des molécules intermédiaires qui permettent de diminuer la distance séparant la bactérie de la cellule-cible. Puisque le sérum est un fluide qui contient de nombreuses molécules, celui-ci a été utilisé comme matériel de départ pour l’isolement de récepteur(s) potentiels. Nous avons isolé un récepteur potentiel à partir du sérum porcin : l’apolipoprotéine A-I. L’interaction entre l’apolipoprotéine A-I et AIDA-I a été confirmée par ELISA et microscopie à fluorescence. La capacité à envahir les cellules épithéliales offre aux pathogènes la possibilité d’établir une niche intracellulaire qui les protègent contre les attaques du milieu extérieur. La présente étude a démontré que la présence d’AIDA-I en tant que seul facteur de virulence chez une souche de laboratoire permet de conférer la capacité d’envahir les cellules sans promouvoir la survie intracellulaire. L’étude de la souche sauvage 2787, exprimant AIDA-I en association avec d’autres facteurs de virulence, a démontré une différence significative pour les phénotypes d’invasion et de survie intracellulaire face à la souche de laboratoire exprimant AIDA-I. / The adhesin involved in diffuse adherence (AIDA-I) is a bacterial adhesin associated with some Escherichia coli strains that might, when associated with toxin Stx2e or STb, contribute to the development of edema disease or post-weaning diarrhea in piglets. AIDA-I is an autotransporter that mediates various phenotypes such as adhesion, autoaggregation and biofilm formation. The main aim of our project was to find potential receptor(s) for AIDA-I. Pathogens can either bind cell directly by targeting exposed cell surface molecules or use an intermediate molecule as a bridge to lessen the space separating them from their target cell. Serum is known to contain a wide range of molecules so it has been used as raw material for the isolation of a putative receptor for AIDA-I. We isolated a putative receptor for AIDA-I: the apolipoprotein A-I. The interaction between the apolipoprotein A-I and AIDA-I was confirmed by ELISA and fluorescent microscopy. The capacity to invade epithelial cell enables pathogens to create an intracellular niche that protects them against attacks from the extracellular environment. The present report has shown that the presence of AIDA-I as the sole virulence factor in a laboratory strain, enable bacteria to invade cultured cells but does not promote intracellular survival. Studies conducted on wild-type strain 2787, which express AIDA-I in association with other virulence factors, has shown a significant difference in invasion and intracellular survival phenotypes compared to the laboratory strain expressing AIDA-I.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

L’implication des protéines tyrosines phosphatases (PTPs) dans la régulation de la signalisation et la médiation des fonctions cellulaires a été bien établie dans les dernières années. Cependant, les mécanismes moléculaires par lesquels les PTPs régulent les processus fondamentaux tels que l’angiogenèse demeurent méconnus. Il a été rapporté que l’expression de la PTP DEP-1 (Density-enhanced phosphatase 1) augmente avec la densité cellulaire et corrèle avec la déphosphorylation du récepteur VEGFR2. Cette déphosphorylation contribue à l’inhibition de contact dans les cellules endothéliales à confluence et diminue l’activité du VEGFR2 en déphosphorylant spécifiquement ses résidus catalytiques Y1054/1059. De plus, la plupart des voies de signalisation en aval du VEGFR2 sont diminuées sauf la voie Src-Gab1-AKT. DEP-1 déphosphoryle la Y529 de Src et contribue à la promotion de la survie dans les cellules endothéliales. L’objectif de cette thèse est de mieux définir le rôle de DEP-1 dans la régulation de l’activité de Src et les réponses biologiques dans les cellules endothéliales. Nous avons identifié les résidus Y1311 et Y1320 dans la queue C-terminale de DEP-1 comme sites majeurs de phosphorylation en réponse au VEGF. La phosphorylation de ces résidus est requise pour l’activation de Src et médie le remodelage des jonctions cellules-cellules dépendantes de Src. Ce remodelage induit la perméabilité, l’invasion et la formation de capillaires en réponse au VEGF. Nos résultats démontrent que la phosphorylation de DEP-1 sur résidu tyrosine est requise pour diriger la spécificité de DEP-1 vers son substrat Src. Les travaux révèlent pour la première fois un rôle positif de DEP-1 sur l’induction du programme angiogénique des cellules endothéliales. En plus de la phosphorylation sur tyrosine, DEP-1 est constitutivement phosphorylé sur la thréonine 1318 situé à proximité de la Y1320 en C-terminal. Cette localisation de la T1318 suggère que ce résidu pourrait être impliqué dans la régulation de la Y1320. En effet, nous avons observé que la T1318 de DEP-1 est phosphorylée potentiellement par CK2, et que cette phosphorylation régule la phosphorylation de DEP-1 sur tyrosine et sa capacité de lier et d’activer Src. En accord avec ces résultats, nos travaux révèlent que la surexpression du mutant DEP-1 T1318A diminue le remodelage des jonctions cellules-cellules et par conséquent la perméabilité. Nos résultats suggèrent donc que la T1318 de DEP-1 constitue un nouveau mécanisme de contrôle de la phosphorylation sur tyrosine et que ceci résulte en l’activation de Src et l’induction des fonctions biologiques des cellules endothéliales en réponse au VEGF. Suite à ces travaux dans les cellules endothéliales qui démontrent un rôle positif de DEP-1 dans la médiation des réponses angiogéniques, nous avons voulu approfondir nos connaissances sur l’implication potentielle de DEP-1 dans les cellules cancéreuses où l’activité de Src est requise pour la progression tumorale. Malgré le rôle connu de DEP-1 comme suppresseur tumoral dans différents types de cancer, nous avons émis l’hypothèse que DEP-1 pourrait promouvoir les fonctions biologiques dépendantes de Src telles que la migration et l’invasion dans les cellules cancéreuses. Ainsi, nous avons observé que l’expression de DEP-1 est plus élevée dans les lignées basales de cancer du sein qui sont plus invasives comparativement aux lignées luminales peu invasives. Dans les lignées basales, DEP-1 active Src, médie la motilité cellulaire dépendante de Src et régule la localisation des protéines impliquées dans l’organisation du cytosquelette. L’analyse d’un micro-étalage de tissu a révélé que l’expression de DEP-1 est associée avec une réduction tendencielle de survie des patients. Nos résultats proposent donc, un rôle de promoteur tumoral pour DEP-1 dans la progression du cancer du sein. Les travaux présentés dans cette thèse démontrent pour la première fois que DEP-1 peut agir comme promoteur des réponses angiogéniques et du phénotype pro-invasif des lignées basales du cancer du sein probablement du à sa capacité d’activer Src. Nos résultats suggèrent ainsi que l’expression de DEP-1 pourrait contribuer à la progression tumorale et la formation de métastases. Ces découvertes laissent donc entrevoir que DEP-1 représente une nouvelle cible thérapeutique potentielle pour contrer l’angiogenèse et le développement du cancer. / The implication of protein tyrosine phosphatases (PTPs) in the regulation of cell signalling events and the mediation of cellular functions in response to growth factors such as VEGF has been well-established in the last years. Nonetheless, molecular mechanisms by which PTPs regulate fundamental processes such as angiogenesis are not well-characterized. Expression of the PTP DEP-1 (Density-enhanced phosphatase 1) was reported to increase with cell density and was associated with VEGFR2 dephosphorylation contributing to cell contact inhibition in confluent endothelial cells. We previously demonstrated that DEP-1 attenuates VEGFR2 activity by dephosphorylation of its Y1054/1059 leading to decreased activation of major signalling pathways downstream of VEGFR2 with exception of the Src-Gab1-AKT pathway. Increasing Src activity due to DEP-1-mediated dephosphorylation of its Y529 promotes endothelial cell survival. The objective of this thesis was to gain a better understanding of the role of DEP-1 in the regulation of the Src activity and of biological responses in endothelial cells. We identified tyrosine Y1311 and Y1320 in the C-terminal tail of DEP-1 as major phosphorylation sites in response to VEGF. These residues are required for Src activation and mediate the Src-dependent remodelling of endothelial cell junctions inducing permeability, invasion and capillary formation upon VEGF stimulation. We showed that VEGF-induced DEP-1 tyrosine phosphorylation directs DEP-1 specificity towards its substrate Src. Our results thus highlighted for the first time the promoting role of DEP-1 on the angiogenic program in endothelial cells. In addition to tyrosine phosphorylation, DEP-1 is constitutively phosphorylated on a threonine residue (T1318) proximal to Y1320 in its C-terminal tail suggesting it might be involved in the regulation of Y1320. Indeed, we found that DEP-1 T1318 is phosphorylated, potentially by CK2, and regulates the tyrosine phosphorylation of DEP-1 and its ability to bind to and activate Src. Consistent with this, remodelling of endothelial cell junctions and permeability are impaired in endothelial cells expressing the DEP-1 T1318 mutant. Thus, DEP-1 phosphorylation on T1318 displays a regulatory control over DEP-1 tyrosine phosphorylation and subsequently Src activation and endothelial cell functions in response to VEGF. Our results demonstrating that DEP-1 promotes angiogenic cell responses in endothelial cells, prompted us to consider a possible involvement of DEP-1 in cancer cells, where Src activation has been linked to cancer progression. Thus, although, DEP-1 is believed to act as a tumour suppressor in different cancer types, we hypothesized that it might also promote Src-dependent functions such as migration and invasion in cancer cells. Interestingly, we found that DEP-1 is higher expressed in more invasive basal-like breast cancer cells than in luminal-like cell lines. Moreover, DEP-1 is implicated in the regulation of Src activity, Src-mediated cell motility and appropriate localization of proteins mediating cytoskeletal organization in basal-like breast cancer cell lines. To further support these results, analysis of a breast cancer tissue microarray revealed that DEP-1 expression is associated with a tendency towards reduced overall survival. Thus, our results provide first evidence for a tumour-promoting role of DEP-1 in breast cancer. Altogether, the work performed in the context of this thesis revealed that DEP-1 can similarly behave as a promoter of the angiogenic response and of the pro-invasive phenotype in basal-like breast cancer cell lines, most likely due to its ability to activate Src. This suggests for the first time that DEP-1 expression could contribute to tumour progression and the formation of metastases, and as such, represent a potential new target for anti-angiogenic and anti-cancer therapy.

7 Abstract Protein kinase C alpha (PKCα) is a serine/threonine protein kinase. PKCα is an important protein regulating cell polarity, protein secretion, apoptosis, cell proliferation and differentiation and tumorogenesis. Previous research has shown a role of PKCα also in a cancer cell migration and cancer cell invasion. The aim of this study was to investigate the role of protein kinase C alpha (PKCα) played in amoeboid mode of cancer cell invasion. We showed that higher expression of PKCα resulted in mesenchymal-amoeboid transition of K2 and MDA mesenchymal cancer cell lines, which was accompanied with decreased cancer cell invasive capability in 3D collage matrix. PKCα overexpression had no effect on the cell morphology of A375m2, however, the results showed a trend in increased invasive potential of A375m2 cells. Conversely, the expression of dominant-negative PKCα resulted in amoeboid-mesenchymal transition of A375m2 cells, and it was associated with decreased invasive potential of K2 and MDA cell lines. Furthermore, a linkage between PKCα and phosphatidylinositol 3-kinase (PI3K) was tested. The results revealed that increased activity of PKCα was accompanied with decreased level of active Akt in K2 cell line. To summarize, our results suggest a probable role of PKCα in regulation of amoeboid...

L’invasion des ostéoblastes par Staphylococcus aureus (SA) est considérée comme responsable, au moins partiellement, de l’évolution chronique ou récurrente des infections osseuses (IO). Nous avons émis l’hypothèse que des différences d’interactions SA-ostéoblastes pouvaient être associées aux différences de présentation clinique des IO. Nous avons d’abord développé un modèle ex vivo d’infection intracellulaire d’ostéoblastes humains permettant de quantifier l’adhésion, l’invasion, la survie intracellulaire de SA et les dommages subis par les cellules infectées. Grâce ce modèle, nous avons montré que les SA communautaires résistants à la méticilline (CA-MRSA), un groupe polyphylétique de souches hypervirulentes associées à des formes aiguës et sévères d’IO, induisent une cytotoxicité supérieure à celle des MRSA hospitaliers (HA-MRSA) associés à des IO plus souvent chroniques. A l’aide de mutants isogéniques, nous avons pu démontrer que cette cytotoxicité était indépendante de la toxine de Panton-Valentine et l’alphahémolysine mais associée à la surexpression des phenol-soluble modulins (PSM) par les CA-MRSA. Ces résultats ont permis d’identifier un nouveau mécanisme de virulence des CA-MRSA basé sur l’invasion des ostéoblastes et l’activité intracellulaire des PSM. Parallèlement, nous avons montré que certains antibiotiques modifient le niveau de transcription et d’expression des protéines staphylococciques impliquées dans l’invasion des ostéoblastes, sans que nous ne puissions montrer une modification de la capacité d’invasion de S. aureus dans ce même modèle ex vivo. Nos travaux ouvrent de nouvelles perspectives dans la compréhension et la prise en charge des IO due à SA / Osteoblast invasion by Staphylococcus aureus (SA) is currently considered a putative explanatory mechanism for the chronic or recurrent nature of osteomyelitis. We raised the hypothesis that inter-strain differences in the interactions between S. aureus and osteoblasts at the cellular level could correlate with differences in the clinical presentation of osteomyelitis. We first developed an ex vivo model of intracellular bacterial challenge of human osteoblasts to quantify SA adhesion, invasion and intracellular survival as well as SA-induced damage to infected cells. By means of this model, we have demonstrated that community-acquired methicillinresistant SA (CA-MRSA) strains, which belong to a polyphyletic group endowed with high virulence and are associated with severe and acute forms of osteomyelitis, induce more cytotoxicity in osteoblasts as compared to hospital MRSA strains, which in turn are more frequently involved in chronic forms of osteomyelitis. Using isogenic CA-MRSA mutants, we determined that SA-induced osteoblast damage was independent of the production of Panton-Valentin leukocidin and alpha-toxin, but was associated with the overexpression of phenol-soluble modulins (PSMs) by CAMRSA. These findings elucidate a novel virulence strategy of CA-MRSA based on the invasion and PSM-related killing of osteoblasts. In parallel to this research, we demonstrated that several antibiotics alter the transcription and expression levels of SA adhesins involved in osteoblast invasion. However, antibiotics did not induce changes in SA invasiveness in our ex vivo infection model. Collectively, our findings provide new insights into the pathogenesis of SA osteomyelitis

Cette thèse porte sur la trajectoire éditoriale et artistique de la collection Vertigo créée en 1993 par DC Comics, maison d’édition états-unienne spécialisée dans la bande dessinée. Je me propose d’aborder Vertigo à travers l'apport des scénaristes britanniques employés par DC Comics depuis le milieu des années quatre-vingt. Leur rôle est en effet considérable, tant au moment de la fondation de Vertigo par la rédactrice Karen Berger que dans le succès ultérieur dont jouit la collection. La genèse de Vertigo met en lumière l’importance du phénomène appelé l’ « Invasion britannique », c’est-à-dire l’arrivée sur le marché états-unien de nombreux créateurs qui sont nés et travaillent à l’étranger pour DC Comics. Cette « invasion » révélera au public américain des scénaristes de tout premier plan tels Alan Moore, Grant Morrison ou Neil Gaiman, dont la série The Sandman est considérée comme un jalon majeur de l’histoire du média. La critique existante au sujet de Vertigo en général tend d’ailleurs à se focaliser sur la portion du corpus produit par les Britanniques, mais sans nécessairement prendre acte de cette spécificité culturelle. Le travail à mener est donc double ; d'une part, il s'agira de retracer une histoire du label en tant qu'instance productrice d'une culture médiatique particulière, qui s'inscrit dans un contexte socio-historique et repose sur les pratiques et les représentations de l'ensemble des acteurs (producteurs et consommateurs au sens large), eux-mêmes nourris d'une tradition qui préexiste à l'apparition de Vertigo. Il sera dès lors possible de prendre appui sur cette connaissance contextuelle pour interroger la poétique du label, et ainsi identifier les spécificités d’une « école » britannique au sein de cette industrie culturelle. / This thesis deals with the editorial and aesthetic history of the Vertigo imprint, which was created in 1993 by DC Comics, a US-American comics publisher. I shall consider in particular the contribution of British scriptwriters employed by DC and then by Vertigo from the 1980s onwards. Theise creators played a tremendous role, both at the time of Vertigo's founding by editor Karen Berger and at a later date, as the imprint gathered widespread recognition. The genesis of the Vertigo imprint sheds light on the so-called “British Invasion”, that is to say the appearance within the American industry of several UK-based creators working for DC Comics. Spearheaded by Alan Moore, the “invasion” brought to the fore many of the most important scriptwriters of years to come, such as Grant Morrison and Neil Gaiman, whose Sandman series has been described as a major landmark in the recognition of the medium. Existing criticism regarding Vertigo tends to focus on the body of work produced by British authors, without necessarily discussing their national specificity. My goal is therefore double; on the one hand, I intend to write a history of the label as the producer of a specific media culture that belongs to a given socio-historical context and is grounded in the practices and representations of the field's actors (producers and consumers in a broad sense). On the other hand, the awareness of the context in which the books are produced shall allow me to interrogate the imprint's poetics, thus identifying the specificity of a “British school of writing” within the comics mainstream industry.

1. Abstract Protein kinase C α (PKCα) is a serine/threonine protein kinase regulating many different signaling pathways. The aim of this study was to investigate the potential role of PKCα in amoeboid morphology and invasion of cancer cells. It was observed, that expression of PKCα as well as its phosphorylation on Thr497 remained unchanged upon amoeboid-mesenchymal transition of A375m2 cells (induced by inhibition of ROCK kinase) both in 3D and in 2D environment. However, activation of PKCα by PKC activator treatment resulted in mesenchymal- amoeboid transition of K2 and MDA-MB-231 mesenchymal cell lines, although it did not change overall invasivity ability of cells to invade 3D collagen. Notably, PKCα activation significantly reduced matrix degrading abilities of A375m2 cells. Conversely, inhibition of PKCα by PKCα inhibitor treatment caused amoeboid-mesenchymal transition of amoeboid A375m2 cells and it was associated with decreased invasiveness of all three cell lines used. PKCα inhibitor did not have any effect on gelatin degradation area of A375m2 cells. Consistently, specific siRNA mediated downregulation of PKCα lead to transition from amoeboid to mesenchymal morphology of A375m2 cells and reduced invasiveness of cells into 3D collagen. Moreover, gelatin degrading abilities of A375m2 cells were...

No description available.

Nuclear magnetic resonance (NMR) has become an effective borehole measurement option to assess petrophysical and fluid properties of porous and permeable rocks. In the case of fluid typing, two-dimensional (2D) NMR interpretation techniques have advantages over conventional one-dimensional (1D) interpretation as they provide additional discriminatory information about saturating fluids and their properties. However, often there is ambiguity as to whether fluids detected with NMR measurements are mobile or residual. In some instances, rapid vertical variations of rock properties (e.g. across thinly-bedded formations) can make it difficult to separate NMR fluid signatures from those due to pore-size distributions. There are also cases where conventional fluid identification methods based on resistivity and nuclear logs indicate dominant presence of water while NMR measurements indicate presence of water, hydrocarbon, and mud filtrate. In such cases, it is important to ascertain whether existing hydrocarbons are residual or mobile. The radial lengths of investigation of resistivity, nuclear, and NMR measurements are very different, with NMR measurements being the shallowest sensing. Even in the case of several radial zones of NMR response attributed to different acquisition frequencies and DC magnetic field gradients, the measured signal originates from a fairly shallow radial zone compared to that of nuclear and resistivity logs. Depending on drilling mud being used and the radial extent of mud-filtrate invasion, the NMR response of virgin reservoir fluids can be masked by mud filtrate because of fluid displacement and mixing. In order to separate those effects, it is important to reconcile NMR measurements with electrical and nuclear logs for improved assessment of porosity and mobile hydrocarbon saturation. Previously, Voss et al. (2009) and Gandhi et al. (2010) introduced the concept of Common Stratigraphic Framework (CSF) to construct and validate multi-layer static and dynamic petrophysical models based on the numerical simulation of well logs. In this thesis, the concept of CSF is implemented to reconcile 2D NMR interpretations with multi-layer static and dynamic petrophysical models. It is found that quantifying the exact radial zone of response and corresponding fluid saturations can only be accomplished with studies of mud-filtrate invasion that honor available resistivity and nuclear logs. This thesis indicates that the two interpretation methods complement each other and when applied in conjunction, improve and refine the overall petrophysical understanding of permeable rock formations. Examples of successful application include field data acquired in thinly-bedded gas formations invaded with water-base mud, where bed-boundary effects are significant and residual hydrocarbon saturation is relatively high. In such cases, numerical simulation of mud-filtrate invasion and well logs acquired after invasion enables reliable interpretations of petrophysical and fluid properties. The interpretation procedure introduced in this thesis also provides an explicit way to determine the uncertainty of petrophysical and fluid interpretations. / text

Well logs and formation testers are routinely used for detection and quantification of hydrocarbon reserves. Overbalanced drilling causes invasion of mud filtrate into permeable rocks, hence radial displacement of in-situ saturating fluids away from the wellbore. The spatial distribution of fluids in the near-wellbore region remains affected by a multitude of petrophysical and fluid factors originating from the process of mud-filtrate invasion. Consequently, depending on the type of drilling mud (e.g. water- and oil-base muds) and the influence of mud filtrate, well logs and formation-tester measurements are sensitive to a combination of in-situ (original) fluids and mud filtrate in addition to petrophysical properties of the invaded formations. This behavior can often impair the reliable assessment of hydrocarbon saturation and formation storage/mobility. The effect of mud-filtrate invasion on well logs and formation-tester measurements acquired in vertical wells has been extensively documented in the past. Much work is still needed to understand and quantify the influence of mud-filtrate invasion on well logs acquired in horizontal and deviated wells, where the spatial distribution of fluids in the near-wellbore region is not axial-symmetric in general, and can be appreciably affected by gravity segregation, permeability anisotropy, capillary pressure, and flow barriers. This dissertation develops a general algorithm to simulate the process of mud-filtrate invasion in vertical and deviated wells for drilling conditions that involve water- and oil-base mud. The algorithm is formulated in cylindrical coordinates to take advantage of the geometrical embedding imposed by the wellbore in the spatial distribution of fluids within invaded formations. In addition, the algorithm reproduces the formation of mudcake due to invasion in permeable formations and allows the simulation of pressure and fractional flow-rate measurements acquired with dual-packer and point-probe formation testers after the onset of invasion. An equation-of-state (EOS) formulation is invoked to simulate invasion with both water- and oil-base muds into rock formations saturated with water, oil, gas, or stable combinations of the three fluids. The algorithm also allows the simulation of physical dispersion, fluid miscibility, and wettability alteration. Discretized fluid flow equations are solved with an implicit pressure and explicit concentration (IMPEC) scheme. Thermodynamic equilibrium and mass balance, together with volume constraint equations govern the time-space evolution of molar and fluid-phase concentrations. Calculations of pressure-volume-temperature (PVT) properties of the hydrocarbon phase are performed with Peng-Robinson's equation of state. A full-tensor permeability formulation is implemented with mass balance equations to accurately model fluid flow behavior in horizontal and deviated wells. The simulator is rigorously and successfully verified with both analytical solutions and commercial simulators. Numerical simulations performed over a wide range of fluid and petrophysical conditions confirm the strong influence that well deviation angle can have on the spatial distribution of fluid saturation resulting from invasion, especially in the vicinity of flow barriers. Analysis on the effect of physical dispersion on the radial distribution of salt concentration shows that electrical resistivity logs could be greatly affected by salt dispersivity when the invading fluid has lower salinity than in-situ water. The effect of emulsifiers and oil-wetting agents present in oil-base mud was studied to quantify wettability alteration and changes in residual water saturation. It was found that wettability alteration releases a fraction of otherwise irreducible water during invasion and this causes electrical resistivity logs to exhibit an abnormal trend from shallow- to deep-sensing apparent resistivity. Simulation of formation-tester measurements acquired in deviated wells indicates that (i) invasion increases the pressure drop during both drawdown and buildup regimes, (ii) bed-boundary effects increase as the wellbore deviation angle increases, and (iii) a probe facing upward around the perimeter of the wellbore achieves the fastest fluid clean-up when the density of invading fluid is larger than that of in-situ fluid. / text