940 resultados para 3-D velocity around tidal fronts
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PURPOSE: To assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. PATIENTS AND METHODS: Between 1983-2000, 122 consecutive patients treated for early laryngeal cancer (UICC T1N0 and T2N0) by radical radiation therapy (RT) were retrospectively studied. Male-to-female ratio was 106 : 16, and median age 62 years (35-92 years). There were 68 patients with T1a, 18 with T1b, and 36 with T2 tumors. Diagnosis was made by biopsy in 104 patients, and by laser vaporization or stripping in 18. Treatment planning consisted of three-dimensional (3-D) conformal RT in 49 (40%) patients including nine patients irradiated using arytenoid protection. A median dose of 70 Gy (60-74 Gy) was given (2 Gy/fraction) over a median period of 46 days (21-79 days). Median follow-up period was 85 months. RESULTS: The 5-year overall, cancer-specific, and disease-free survival amounted to 80%, 94%, and 70%, respectively. 5-year local control was 83%. Median time to local recurrence in 19 patients was 13 months (5-58 months). Salvage treatment consisted of surgery in 17 patients (one patient refused salvage and one was inoperable; total laryngectomy in eleven, and partial laryngectomy or cordectomy in six patients). Six patients died because of laryngeal cancer. Univariate analyses revealed that prognostic factors negatively influencing local control were anterior commissure extension, arytenoid protection, and total RT dose < 66 Gy. Among the factors analyzed, multivariate analysis (Cox model) demonstrated that anterior commissure extension, arytenoid protection, and male gender were the worst independent prognostic factors in terms of local control. CONCLUSION: For early-stage laryngeal cancer, outcome after RT is excellent. In case of anterior commissure extension, surgery or higher RT doses are warranted. Because of a high relapse risk, arytenoid protection should not be attempted.
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Site-directed mutagenesis and molecular dynamics analysis of the 3-D model of the alpha1B-adrenergic receptor (AR) were combined to identify the molecular determinants of the receptor involved in catecholamine binding. Our results indicate that the three conserved serines in the fifth transmembrane domain (TMD) of the alpha1B-AR play a distinct role in catecholamine binding versus receptor activation. In addition to the amino acids D125 in TMDIII and S207 in TMDV directly involved in ligand binding, our findings identify a large number of polar residues playing an important role in the activation process of the alpha1B-AR thus providing new insights into the structure/function relationship of G protein-coupled receptors.
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BACKGROUND: Glioblastoma, the most common adult primary malignant brain tumor, confers poor prognosis (median survival of 15 months) notwithstanding aggressive treatment. Combination chemotherapy including carmustine (BCNU) or temozolomide (TMZ) with the MGMT inhibitor O6-benzylguanine (O6BG) has been used, but has been associated with dose-limiting hematopoietic toxicity. OBJECTIVE: To assess safety and efficacy of a retroviral vector encoding the O6BG-resistant MGMTP140K gene for transduction and autologous transplantation of hematopoietic stem cells (HSCs) in MGMT unmethylated, newly diagnosed glioblastoma patients in an attempt to chemoprotect bone marrowduring combination O6BG/TMZ therapy. METHODS: Three patients have been enrolled in the first cohort. Patients underwent standard radiation therapy without TMZ followed by G-CSF mobilization, apheresis, and conditioning with 600 mg/m2 BCNU prior to infusion of gene-modified cells. Posttransplant, patients were treated with 28-day cycles of single doseTMZ (472 mg/m2) with 48-hour intravenous O6BG (120 mg/m2 bolus, then 30 mg/m2/d). RESULTS: The BCNU dose was nonmyeloablative with ANC ,500/mL for ≤3 d and nadir thrombocytopenia of 28,000/mL. Gene marking in pre-infusion colony forming units (CFUs) was 70.6%, 79.0%, and 74.0% in Patients 1, 2, and 3, respectively, by CFU-PCR. Following engraftment, gene marking in white blood cells and sorted granulocytes ranged between 0.37-0.84 and 0.33-0.83 provirus copies, respectively, by real-time PCR. Posttransplant gene marking in CFUs from CD34-selected cells ranged from 28.5% to 47.4%. Patients have received 4, 3, and 2 cycles of O6BG/TMZ, respectively, with evidence for selection of gene-modified cells. One patient has received a single dose-escalated cycle at 590 mg/m2 TMZ. No additional extra-hematopoietic toxicity has been observed thus far and all three patients exhibit stable disease at 7-8 months since diagnosis CONCLUSIONS: We believe that these data demonstrate the feasibility of achieving significant engraftment of MGMTP140K-modified cells with a well-tolerated dose of BCNU. Further follow-up will determine whether this approach will allow for further dose escalation of TMZ and improved survival.
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The registration of full 3-D models is an important task in computer vision. Range finders only reconstruct a partial view of the object. Many authors have proposed several techniques to register 3D surfaces from multiple views in which there are basically two aspects to consider. First, poor registration in which some sort of correspondences are established. Second, accurate registration in order to obtain a better solution. A survey of the most common techniques is presented and includes experimental results of some of them
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The association between land use and land cover changes between 1979-2004 in a 2.26-million-hectare area south of the Gran Chaco region and Trypanosoma cruzi infection in rural communities was analysed. The extent of cultural land, open and closed forests and shrubland up to 3,000 m around rural communities in the north, northwest and west of the province of Córdoba was estimated using Landsat satellite imagery. The T. cruzi prevalence was estimated with a cross-sectional serological survey conducted in the rural communities. The land cover showed the same patterns in the 1979, 1999 and 2004 satellite imagery in both the northwest and west regions, with shrinking regions of cultured land and expanding closed forests away from the community. The closed forests and agricultural land coverage in the north region showed the same trend as in the northwest and west regions in 1979 but not in 1999 or 2004. In the latter two years, the coverage remote from the communities was either constant or changed in opposite ways from that of the northwest and west regions. The changes in closed forests and cultured vegetation alone did not have a significant, direct relationship with the occurrence of rural communities with at least one person infected by T. cruzi. This study suggests that the overall decrease in the prevalence of T. cruzi is a consequence of a combined effect of vector control activities and changes in land use and land cover.
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Via a transcription factor, Foxp3, immunoregulatory CD4(+)CD25(+) T cells (T reg cells) play an important role in suppressing the function of other T cells. Adoptively transferring high numbers of T reg cells can reduce the intensity of the immune response, thereby providing an attractive prospect for inducing tolerance. Extending our previous findings, we describe an in vivo approach for inducing rapid expansion of T reg cells by injecting mice with interleukin (IL)-2 mixed with a particular IL-2 monoclonal antibody (mAb). Injection of these IL-2-IL-2 mAb complexes for a short period of 3 d induces a marked (>10-fold) increase in T reg cell numbers in many organs, including the liver and gut as well as the spleen and lymph nodes, and a modest increase in the thymus. The expanded T reg cells survive for 1-2 wk and are highly activated and display superior suppressive function. Pretreating with the IL-2-IL-2 mAb complexes renders the mice resistant to induction of experimental autoimmune encephalomyelitis; combined with rapamycin, the complexes can also be used to treat ongoing disease. In addition, pretreating mice with the complexes induces tolerance to fully major histocompatibility complex-incompatible pancreatic islets in the absence of immunosuppression. Tolerance is robust and the majority of grafts are accepted indefinitely. The approach described for T reg cell expansion has clinical potential for treating autoimmune disease and promoting organ transplantation.
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L'objectiu d'aquest projecte de final de carrera a l'empresa és el de desenvolupar una eina de catàlegs virtuals per a dispositius del tipus "tablet". Es desenvoluparà només la part client (la del tablet) i per el moment només serà compatible amb tablets amb la versió 3 d'Android o superior, tot i que no es descarta que en properes versions s'ampliarà per a que funcioni també en dispositius mòbils amb versions anteriors. La part servidora ja es té a l'empresa. Aquesta eina ha de servir per a que les empreses l'utilitzin com a suport de vendes, de tal manera que es puguin estalviar els costos que suposa la creació i constant renovació d'un catàleg en paper.
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Insect eggs represent a threat for the plant as hatching larvae rapidly start with their feeding activity. Using a whole-genome microarray, we studied the expression profile of Arabidopsis (Arabidopsis thaliana) leaves after oviposition by two pierid butterflies. For Pieris brassicae, the deposition of egg batches changed the expression of hundreds of genes over a period of 3 d after oviposition. The transcript signature was similar to that observed during a hypersensitive response or in lesion-mimic mutants, including the induction of defense and stress-related genes and the repression of genes involved in growth and photosynthesis. Deposition of single eggs by Pieris rapae caused a similar although much weaker transcriptional response. Analysis of the jasmonic acid and salicylic acid mutants coi1-1 and sid2-1 indicated that the response to egg deposition is mostly independent of these signaling pathways. Histochemical analyses showed that egg deposition is causing a localized cell death, accompanied by the accumulation of callose, and the production of reactive oxygen species. In addition, activation of the pathogenesis-related1::beta-glucuronidase reporter gene correlated precisely with the site of egg deposition and was also triggered by crude egg extract. This study provides molecular evidence for the detection of egg deposition by Arabidopsis plants and suggests that oviposition causes a localized response with strong similarity to a hypersensitive response.
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Introduction: The beneficial effect of physical exercise on bone mineral density (BMD) is at least partly explained by the forces exerted directly on the bones. Male runners present generally higher BMD than sedentary individuals. We postulated that the proximal tibia BMD is related to the running distance as well as to the magnitude of the shocks (while running) in male runners. Methods: A prospective study (three yearly measurements) included 81 healthy male subjects: 16 sedentary lean subjects and three groups of runners (5-30 km/week, n=19; 30-50 km/week, n=29; 50-100 km/week, n=17). Several measurements were performed at the proximal tibia level: volumetric BMD (vBMD), cortical index (CI) i.e. an index of cortical bone thickness and peak accelerations (an index of shocks during heel strike) while running (measured by a 3-D accelerometer). A general linear model assessed the prediction of vBMD or CI by a) simple effects (running distance, peak accelerations, time) and b) interactions (for instance if vBMD prediction by peak acceleration depends on running distance). Results: CI and vBMD a) increase with running distance to reach a plateau over 30 km/wk, b) are positively associated with peak accelerations over 30 km/week. Discussion: Running may be associated with high peak accelerations in order to have beneficial effects on BMD. More important strains are needed to be associated with the same increase in BMD during running sessions of short duration than those of long duration. Conclusion: CI and vBMD are associated with the magnitude of the shocks during heel strike in runners. Key words: Bone mineral density, strains, physical exercise, running distance.
Evolutionary history and its relevance in understanding and conserving southern African biodiversity
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Abstract : Understanding how biodiversity is distributed is central to any conservation effort and has traditionally been based on niche modeling and the causal relationship between spatial distribution of organisms and their environment. More recently, the study of species' evolutionary history and relatedness has permeated the fields of ecology and conservation and, coupled with spatial predictions, provides useful insights to the origin of current biodiversity patterns, community structuring and potential vulnerability to extinction. This thesis explores several key ecological questions by combining the fields of niche modeling and phylogenetics and using important components of southern African biodiversity. The aims of this thesis are to provide comparisons of biodiversity measures, to assess how climate change will affect evolutionary history loss, to ask whether there is a clear link between evolutionary history and morphology and to investigate the potential role of relatedness in macro-climatic niche structuring. The first part of my thesis provides a fine scale comparison and spatial overlap quantification of species richness and phylogenetic diversity predictions for one of the most diverse plant families in the Cape Floristic Region (CFR), the Proteaceae. In several of the measures used, patterns do not match sufficiently to argue that species relatedness information is implicit in species richness patterns. The second part of my thesis predicts how climate change may affect threat and potential extinction of southern African animal and plant taxa. I compare present and future niche models to assess whether predicted species extinction will result in higher or lower V phylogenetic diversity survival than what would be experienced under random extinction processes. l find that predicted extinction will result in lower phylogenetic diversity survival but that this non-random pattern will be detected only after a substantial proportion of the taxa in each group has been lost. The third part of my thesis explores the relationship between phylogenetic and morphological distance in southern African bats to assess whether long evolutionary histories correspond to equally high levels of morphological variation, as predicted by a neutral model of character evolution. I find no such evidence; on the contrary weak negative trends are detected for this group, as well as in simulations of both neutral and convergent character evolution. Finally, I ask whether spatial and climatic niche occupancy in southern African bats is influenced by evolutionary history or not. I relate divergence time between species pairs to climatic niche and range overlap and find no evidence for clear phylogenetic structuring. I argue that this may be due to particularly high levels of micro-niche partitioning. Résumé : Comprendre la distribution de la biodiversité représente un enjeu majeur pour la conservation de la nature. Les analyses se basent le plus souvent sur la modélisation de la niche écologique à travers l'étude des relations causales entre la distribution spatiale des organismes et leur environnement. Depuis peu, l'étude de l'histoire évolutive des organismes est également utilisée dans les domaines de l'écologie et de la conservation. En combinaison avec la modélisation de la distribution spatiale des organismes, cette nouvelle approche fournit des informations pertinentes pour mieux comprendre l'origine des patterns de biodiversité actuels, de la structuration des communautés et des risques potentiels d'extinction. Cette thèse explore plusieurs grandes questions écologiques, en combinant les domaines de la modélisation de la niche et de la phylogénétique. Elle s'applique aux composants importants de la biodiversité de l'Afrique australe. Les objectifs de cette thèse ont été l) de comparer différentes mesures de la biodiversité, 2) d'évaluer l'impact des changements climatiques à venir sur la perte de diversité phylogénétique, 3) d'analyser le lien potentiel entre diversité phylogénétique et diversité morphologique et 4) d'étudier le rôle potentiel de la phylogénie sur la structuration des niches macro-climatiques des espèces. La première partie de cette thèse fournit une comparaison spatiale, et une quantification du chevauchement, entre des prévisions de richesse spécifique et des prédictions de la diversité phylogénétique pour l'une des familles de plantes les plus riches en espèces de la région floristique du Cap (CFR), les Proteaceae. Il résulte des analyses que plusieurs mesures de diversité phylogénétique montraient des distributions spatiales différentes de la richesse spécifique, habituellement utilisée pour édicter des mesures de conservation. La deuxième partie évalue les effets potentiels des changements climatiques attendus sur les taux d'extinction d'animaux et de plantes de l'Afrique australe. Pour cela, des modèles de distribution d'espèces actuels et futurs ont permis de déterminer si l'extinction des espèces se traduira par une plus grande ou une plus petite perte de diversité phylogénétique en comparaison à un processus d'extinction aléatoire. Les résultats ont effectivement montré que l'extinction des espèces liées aux changements climatiques pourrait entraîner une perte plus grande de diversité phylogénétique. Cependant, cette perte ne serait plus grande que celle liée à un processus d'extinction aléatoire qu'à partir d'une forte perte de taxons dans chaque groupe. La troisième partie de cette thèse explore la relation entre distances phylogénétiques et morphologiques d'espèces de chauves-souris de l'Afrique australe. ll s'agit plus précisément de déterminer si une longue histoire évolutive correspond également à des variations morphologiques plus grandes dans ce groupe. Cette relation est en fait prédite par un modèle neutre d'évolution de caractères. Aucune évidence de cette relation n'a émergé des analyses. Au contraire, des tendances négatives ont été détectées, ce qui représenterait la conséquence d'une évolution convergente entre clades et des niveaux élevés de cloisonnement pour chaque clade. Enfin, la dernière partie présente une étude sur la répartition de la niche climatique des chauves-souris de l'Afrique australe. Dans cette étude je rapporte temps de divergence évolutive (ou deux espèces ont divergé depuis un ancêtre commun) au niveau de chevauchement de leurs niches climatiques. Les résultats n'ont pas pu mettre en évidence de lien entre ces deux paramètres. Les résultats soutiennent plutôt l'idée que cela pourrait être I dû à des niveaux particulièrement élevés de répartition de la niche à échelle fine.
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Esta ponencia se enmarca dentro de la tesis doctoral que estamos escribiendo y que intenta recuperar el legado gráfico del Mirouer des simples ames (c. 1290) de Marguerite Porete. Tanto ella como su tratado fueron sometidos a una persecución inquisitorial que concluyó con el encarcelamiento de la escritora, la prohibición de su tratado y la quema de ambos. A pesar de ello, la obra sobrevivió sustentada por varios códices que la recogen como texto meramente escrito. Nosotros sostenemos que este texto posee un trasfondo visual (que no visionario) que se puede recuperar en forma de iconografía. Las razones para plantear esta hipótesis son muchas, aunque la fundamental reside en su justificación didáctica: estamos ante un tratado que se autodefine como speculum, como miroir, y que, efectivamente, se ha escrito para enseñar a otros el camino hacia la divinidad. Tal camino es complejo y se desarrolla a través de los parajes de un lenguaje teológico violentamente abstracto, que se difundía en ambientes de predicación no necesariamente clericales y letrados: aquí es donde la visualidad se constituye como andamio del discurso, que permite hablar, enseñar, un camino experiencial complejo mediante imágenes comprensibles, incluso memorizables. Para mostrar el cómo de esta recuperación de manera práctica y presentar algunos resultados, analizaremos en este texto uno de los esquemas gráficos que subyacen en el texto poreteano: la alegoría de Ezequiel. Examinaremos primero el pasaje donde se presenta utilizando instrumentos de la filología para dilucidar un hipotético esquema gráfico subyacente, que, en un segundo estadio, vinculamos con otros textos cercanos al Mirouer que, por una razón u otra, sí tienen una iconografía asignada. Comprobaremos qué relación visual sostiene la obra poreteana con temas iconográficos como el Jardín de las virtudes (en, esencialmente, Le somme le roi) o el árbol de Jesé (ídem Speculum Virginum) y observaremos a qué conclusiones histórico-doctrinales nos lleva este estudio comparativo. En suma, intentamos con esta ponencia devolver parte del aspecto histórico-visual al Mirouer des simples ames, con la finalidad de que ello nos permita realizar una lectura hermenéutica más amplia, más justa, del texto.
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In the assessment of medical malpractice imaging methods can be used for the documentation of crucial morphological findings which are indicative for or against an iatrogenically caused injury. The clarification of deaths in this context can be usefully supported by postmortem imaging (primarily native computed tomography, angiography, magnetic resonance imaging). Postmortem imaging offers significant additional information compared to an autopsy in the detection of iatrogenic air embolisms and documentation of misplaced medical aids before dissection with an inherent danger of relocation. Additional information is supplied by postmortem imaging in the search for sources of bleeding as well as the documentation of perfusion after cardiovascular surgery. Key criteria for the decision to perform postmortem imaging can be obtained from the necessary preliminary inspection of clinical documentation.
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BACKGROUND: APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) has antiretroviral activity associated with the hypermutation of viral DNA through cytosine deamination. APOBEC3G has two cytosine deaminase (CDA) domains; the catalytically inactive amino-terminal domain of APOBEC3G (N-CDA) carries the Vif interaction domain. There is no 3-D structure of APOBEC3G solved by X-ray or nuclear magnetic resonance. METHODOLOGY/PRINCIPAL FINDINGS: We predicted the structure of human APOBEC3G based on the crystal structure of APOBEC2. To assess the model structure, we evaluated 48 mutants of APOBEC3G N-CDA that identify novel variants altering DeltaVif HIV-1 infectivity and packaging of APOBEC3G. Results indicated that the key residue D128 is exposed at the surface of the model, with a negative local electrostatic potential. Mutation D128K changes the sign of that local potential. In addition, two novel functionally relevant residues that result in defective APOBEC3G encapsidation, R122 and W127, cluster at the surface. CONCLUSIONS/SIGNIFICANCE: The structure model identifies a cluster of residues important for packaging of APOBEC3G into virions, and may serve to guide functional analysis of APOBEC3G.
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The methodology for generating a homology model of the T1 TCR-PbCS-K(d) class I major histocompatibility complex (MHC) class I complex is presented. The resulting model provides a qualitative explanation of the effect of over 50 different mutations in the region of the complementarity determining region (CDR) loops of the T cell receptor (TCR), the peptide and the MHC's alpha(1)/alpha(2) helices. The peptide is modified by an azido benzoic acid photoreactive group, which is part of the epitope recognized by the TCR. The construction of the model makes use of closely related homologs (the A6 TCR-Tax-HLA A2 complex, the 2C TCR, the 14.3.d TCR Vbeta chain, the 1934.4 TCR Valpha chain, and the H-2 K(b)-ovalbumine peptide), ab initio sampling of CDR loops conformations and experimental data to select from the set of possibilities. The model shows a complex arrangement of the CDR3alpha, CDR1beta, CDR2beta and CDR3beta loops that leads to the highly specific recognition of the photoreactive group. The protocol can be applied systematically to a series of related sequences, permitting the analysis at the structural level of the large TCR repertoire specific for a given peptide-MHC complex.
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Les décisions de gestion des eaux souterraines doivent souvent être justiffées par des modèles quantitatifs d'aquifères qui tiennent compte de l'hétérogénéité des propriétés hydrauliques. Les aquifères fracturés sont parmi les plus hétérogènes et très difficiles à étudier. Dans ceux-ci, les fractures connectées, d'ouverture millimètrique, peuvent agir comme conducteurs hydrauliques et donc créer des écoulements très localisés. Le manque général d'informations sur la distribution spatiale des fractures limite la possibilité de construire des modèles quantitatifs de flux et de transport. Les données qui conditionnent les modèles sont généralement spatialement limitées, bruitées et elles ne représentent que des mesures indirectes de propriétés physiques. Ces limitations aux données peuvent être en partie surmontées en combinant différents types de données, telles que les données hydrologiques et de radar à pénétration de sol plus commun ément appelé géoradar. L'utilisation du géoradar en forage est un outil prometteur pour identiffer les fractures individuelles jusqu'à quelques dizaines de mètres dans la formation. Dans cette thèse, je développe des approches pour combiner le géoradar avec les données hydrologiques affn d'améliorer la caractérisation des aquifères fracturés. Des investigations hydrologiques intensives ont déjà été réalisées à partir de trois forage adjacents dans un aquifère cristallin en Bretagne (France). Néanmoins, la dimension des fractures et la géométrie 3-D des fractures conductives restaient mal connue. Affn d'améliorer la caractérisation du réseau de fractures je propose dans un premier temps un traitement géoradar avancé qui permet l'imagerie des fractures individuellement. Les résultats montrent que les fractures perméables précédemment identiffées dans les forages peuvent être caractérisées géométriquement loin du forage et que les fractures qui ne croisent pas les forages peuvent aussi être identiffées. Les résultats d'une deuxième étude montrent que les données géoradar peuvent suivre le transport d'un traceur salin. Ainsi, les fractures qui font partie du réseau conductif et connecté qui dominent l'écoulement et le transport local sont identiffées. C'est la première fois que le transport d'un traceur salin a pu être imagé sur une dizaines de mètres dans des fractures individuelles. Une troisième étude conffrme ces résultats par des expériences répétées et des essais de traçage supplémentaires dans différentes parties du réseau local. En outre, la combinaison des données de surveillance hydrologique et géoradar fournit la preuve que les variations temporelles d'amplitude des signaux géoradar peuvent nous informer sur les changements relatifs de concentrations de traceurs dans la formation. Par conséquent, les données géoradar et hydrologiques sont complémentaires. Je propose ensuite une approche d'inversion stochastique pour générer des modèles 3-D de fractures discrètes qui sont conditionnés à toutes les données disponibles en respectant leurs incertitudes. La génération stochastique des modèles conditionnés par géoradar est capable de reproduire les connexions hydrauliques observées et leur contribution aux écoulements. L'ensemble des modèles conditionnés fournit des estimations quantitatives des dimensions et de l'organisation spatiale des fractures hydrauliquement importantes. Cette thèse montre clairement que l'imagerie géoradar est un outil utile pour caractériser les fractures. La combinaison de mesures géoradar avec des données hydrologiques permet de conditionner avec succès le réseau de fractures et de fournir des modèles quantitatifs. Les approches présentées peuvent être appliquées dans d'autres types de formations rocheuses fracturées où la roche est électriquement résistive.