977 resultados para Focusing Monochromator
Protective immunity induced in mice by F8.1 and F8.2 antigens purified from Schistosoma mansoni eggs
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Schistosoma mansoni soluble egg antigens (SEA) were fractionated by isoelectric focusing, resulting in 20 components, characterized by pH, absorbance and protein concentration. The higher absorbance fractions were submitted to electrophoresis, and fraction 8 (F8) presented a specific pattern of bands on its isoelectric point. Protein 3 was observed only on F8, and so, it was utilized to rabbit immunization, in order to evaluate its capacity of inducing protective immunity. IgG antibodies from rabbit anti-F8 serum were coupled to Sepharose, and used to obtain the specific antigen by affinity chromatography. This antigen, submitted to electrophoresis, presented two proteic bands (F8.1 and F8.2), which were transferred to nitrocellulose membrane (PVDF) and sequenciated. The homology of F8.2 to known proteins was determined using the Basic Local Alignment Search Tool program (BLASTp). Significant homologies were obtained for the rabbit cytosolic Ca2+ uptake inhibitor, and for the bird a1-proteinase inhibitor. Immunization of mice with F8.1 and F8.2, in the presence of Corynebacterium parvum and Al(OH)3 as adjuvant, induced a significant protection degree against challenge infection, as observed by the decrease on worm burden recovered from portal system.
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Abstract Background: Clinical research in the field of hypertension is now increasingly focusing on the potential effects of antihypertensive treatments that may go beyond the reduction of blood pressure (BP). In particular, renal protection appears as a desirable goal, especially considering that hypertension is associated with an increased risk of developing kidney damage, which may eventually lead to end-stage renal disease and a higher mortality. Dihydropyridine calcium channel blockers (CCBs) are widely used in the field of hypertension therapy but the different renal effects of the various CCBs have been poorly explored to date. Scope: This review will discuss available evidence on the renal effects of two calcium channel blockers: amlodipine and lercanidipine, on the basis of clinical data. Methods: MEDLINE and EMBASE were searched for inclusion of relevant studies. No limitations in time were considered. Results: Results from preclinical and clinical studies suggest that amlodipine is overall less effective in terms of renal protection when compared with other antihypertensive tested agents. Its beneficial effect in retarding the progression of renal disease is achievable only when combined with a blocker of the renin-angiotensin system. Conversely lercanidipine seems to provide renal protection in a similar way to ACE inhibitors, probably thanks to its mechanism of action which acts directly on the afferent and efferent renal arterioles. Conclusions: Treatment of hypertension with CCBs should take into consideration the special effects of each single agent at different levels; lercanidipine for example may play a useful role in the management not only of hypertension but also in renal protection of hypertensive patients.
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L’organització educativa en una escola de música és un aspecte de l’àmbit de coneixement pedagògic que té el seu propi engranatge i un funcionament particular. Mitjançant l’estudi comparatiu entre les escoles municipals de música de Mataró, Olesa de Montserrat i “El Faristol” de Roda de Ter i Santa Maria del Corcó-L’Esquirol, aquest projecte vol donar una visió general de l’organització dels centres de règim especial d’àmbit musical, tot establint les bases teòriques per poder comprendre l’organització educativa de les escoles de música i analitzant tres grans àrees de gestió: el model educatiu, els recursos i el sistema relacional.
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MOTIVATION: Combinatorial interactions of transcription factors with cis-regulatory elements control the dynamic progression through successive cellular states and thus underpin all metazoan development. The construction of network models of cis-regulatory elements, therefore, has the potential to generate fundamental insights into cellular fate and differentiation. Haematopoiesis has long served as a model system to study mammalian differentiation, yet modelling based on experimentally informed cis-regulatory interactions has so far been restricted to pairs of interacting factors. Here, we have generated a Boolean network model based on detailed cis-regulatory functional data connecting 11 haematopoietic stem/progenitor cell (HSPC) regulator genes. RESULTS: Despite its apparent simplicity, the model exhibits surprisingly complex behaviour that we charted using strongly connected components and shortest-path analysis in its Boolean state space. This analysis of our model predicts that HSPCs display heterogeneous expression patterns and possess many intermediate states that can act as 'stepping stones' for the HSPC to achieve a final differentiated state. Importantly, an external perturbation or 'trigger' is required to exit the stem cell state, with distinct triggers characterizing maturation into the various different lineages. By focusing on intermediate states occurring during erythrocyte differentiation, from our model we predicted a novel negative regulation of Fli1 by Gata1, which we confirmed experimentally thus validating our model. In conclusion, we demonstrate that an advanced mammalian regulatory network model based on experimentally validated cis-regulatory interactions has allowed us to make novel, experimentally testable hypotheses about transcriptional mechanisms that control differentiation of mammalian stem cells. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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To assess the impact of international consensus conference guidelines on the attitude of Swiss specialists when facing the decision to treat chronic hepatitis C patients. Questionnaires focusing on the personal situation and treatment decisions were mailed to 165 patients who were newly diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss Hepatitis C Cohort Study during the years 2002-2004. Survey respondents (n = 86, 52.1%) were comparable to non-respondents with respect to severity of liver disease, history of substance abuse and psychiatric co-morbidities. Seventy percent of survey respondents reported having been offered antiviral treatment. Patients deferred from treatment had less advanced liver fibrosis, were more frequently infected with HCV genotypes 1 or 4 and presented more often with a history of depression. There were no differences regarding age, socio-economic background, alcohol abuse, intravenous drug abuse or methadone treatment when compared with patients to whom treatment was proposed. Ninety percent of eligible patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of those considered eligible had actually received antiviral therapy by 2007. Ninety-five percent of patients reported high satisfaction with their own hepatitis C management. Consistent with latest international consensus guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of substance abuse were not withheld antiviral treatment. A multidisciplinary approach is warranted to provide antiviral treatment to patients suffering from depression.
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The investigation of unexplained syncope remains a challenging clinical problem. In the present study we sought to evaluate the diagnostic value of a standardized work-up focusing on non invasive tests in patients with unexplained syncope referred to a syncope clinic, and whether certain combinations of clinical parameters are characteristic of rhythmic and reflex causes of syncope. METHODS AND RESULTS: 317 consecutive patients underwent a standardized work-up including a 12-lead ECG, physical examination, detailed history with screening for syncope-related symptoms using a structured questionnaire followed by carotid sinus massage (CSM), and head-up tilt test. Invasive testings including an electrophysiological study and implantation of a loop recorder were only performed in those with structural heart disease or traumatic syncope. Our work-up identified an etiology in 81% of the patients. Importantly, three quarters of the causes were established non invasively combining head-up tilt test, CSM and hyperventilation testing. Invasive tests yielded an additional 7% of diagnoses. Logistic analysis identified age and number of significant prodromes as the only predictive factors of rhythmic syncope. The same two factors, in addition to the duration of the ECG P-wave, were also predictive of vasovagal and psychogenic syncope. These factors, optimally combined in predictive models, showed a high negative and a modest positive predictive value. CONCLUSION: A standardized work-up focusing on non invasive tests allows to establish more than three quarters of syncope causes. Predictive models based on simple clinical parameters may help to distinguish between rhythmic and other causes of syncope
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The NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response upon infectious insults or tissue injury and damage. However, the role of the NLRP3 inflammasome in natural killer (NK) cell-mediated control of tumor immunity is poorly understood. Here, we show in a model of chemical-induced carcinogenesis and a series of experimental and spontaneous metastases models that mice lacking NLRP3 display significantly reduced tumor burden than control wild-type (WT) mice. The suppression of spontaneous and experimental tumor metastases and methylcholanthrene (MCA)-induced sarcomas in mice deficient for NLRP3 was NK cell and IFN-γ-dependent. Focusing on the amenable B16F10 experimental lung metastases model, we determined that expression of NLRP3 in bone marrow-derived cells was necessary for optimal tumor metastasis. Tumor-driven expansion of CD11b(+)Gr-1(intermediate) (Gr-1(int)) myeloid cells within the lung tumor microenvironment of NLRP3(-/-) mice was coincident with increased lung infiltrating activated NK cells and an enhanced antimetastatic response. The CD11b(+)Gr-1(int) myeloid cells displayed a unique cell surface phenotype and were characterized by their elevated production of CCL5 and CXCL9 chemokines. Adoptive transfer of this population into WT mice enhanced NK cell numbers in, and suppression of, B16F10 lung metastases. Together, these data suggested that NLRP3 is an important suppressor of NK cell-mediated control of carcinogenesis and metastases and identify CD11b(+)Gr-1(int) myeloid cells that promote NK cell antimetastatic function. Cancer Res; 72(22); 5721-32. ©2012 AACR.
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AIMS/HYPOTHESIS: Diabetic macular edema represents the main cause of visual loss in diabetic retinopathy. Besides inner blood retinal barrier breakdown, the role of the outer blood retinal barrier breakdown has been poorly analyzed. We characterized the structural and molecular alterations of the outer blood retinal barrier during the time course of diabetes, focusing on PKCζ, a critical protein for tight junction assembly, known to be overactivated by hyperglycemia. METHODS: Studies were conducted on a type2 diabetes Goto-Kakizaki rat model. PKCζ level and subcellular localization were assessed by immunoblotting and immunohistochemistry. Cell death was detected by TUNEL assays. PKCζ level on specific layers was assessed by laser microdissection followed by Western blotting. The functional role of PKCζ was then evaluated in vivo, using intraocular administration of its specific inhibitor. RESULTS: PKCζ was localized in tight junction protein complexes of the retinal pigment epithelium and in photoreceptors inner segments. Strikingly, in outer segment PKCζ staining was restricted to cone photoreceptors. Short-term hyperglycemia induced activation and delocalization of PKCζ from both retinal pigment epithelium junctions and cone outer segment. Outer blood retinal barrier disruption and photoreceptor cone degeneration characterized long-term hyperglycemia. In vivo, reduction of PKCζ overactivation using a specific inhibitor, restored its tight-junction localization and not only improved the outer blood retinal barrier, but also reduced photoreceptor cell-death. CONCLUSIONS: In the retina, hyperglycemia induced overactivation of PKCζ is associated with outer blood retinal barrier breakdown and photoreceptor degeneration. In vivo, short-term inhibition of PKCζ restores the outer barrier structure and reduces photoreceptor cell death, identifying PKCζ as a potential target for early and underestimated diabetes-induced retinal pathology.
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El papel de la ciudad en el futuro de la humanidad será transcendente, y es que el crecimiento actual de los espacios urbanos tiende, en general, a desbordar el sitio original de las ciudades, abarcando territorios cada vez más extensos y discontinuos. Y por este motivo es de vital importancia el estudio de la ciudad y de su entorno, el cual es sinónimo de ecosistema urbano. En el siguiente estudio se evalúa el ecosistema urbano de San José, capital de Costa Rica, dando énfasis en las zonas verdes presentes, en las relaciones con los ecosistemas naturales circundantes y como mejorar su capacidad ecológica. Por este motivo se ha analizado un proceso de rearborización en el Parque Metropolitano La Sabana, principal nódulo de carga de la trama urbana. Este esfuerzo de naturación dotará al parque de una mayor naturalización, con lo que se espera un aumento de la biodiversidad faunística. Para conocer estos cambios se crea un programa de monitoreo de aves con su respectivo protocolo.
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This article describes the composition of fingermark residue as being a complex system with numerous compounds coming from different sources and evolving over time from the initial composition (corresponding to the composition right after deposition) to the aged composition (corresponding to the evolution of the initial composition over time). This complex system will additionally vary due to effects of numerous influence factors grouped in five different classes: the donor characteristics, the deposition conditions, the substrate nature, the environmental conditions and the applied enhancement techniques. The initial and aged compositions as well as the influence factors are thus considered in this article to provide a qualitative and quantitative review of all compounds identified in fingermark residue up to now. The analytical techniques used to obtain these data are also enumerated. This review highlights the fact that despite the numerous analytical processes that have already been proposed and tested to elucidate fingermark composition, advanced knowledge is still missing. Thus, there is a real need to conduct future research on the composition of fingermark residue, focusing particularly on quantitative measurements, aging kinetics and effects of influence factors. The results of future research are particularly important for advances in fingermark enhancement and dating technique developments.
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This paper aims to analyse the impact of human capital on business productivity, focusing the analysis on the possible effect of the complementarity that exists between human capital and new production technologies, particularly advanced manufacturing technologies (AMTs) for the specific case of small and medium enterprises (SMEs) in Catalonia. Additionally, following the theory of skill-biased technological change, the paper analyses whether technological change produces bias exclusively in the skills required for managers, or whether the bias extends to the skills required of production staff. With this objective, we have compared the possible existence of complementarity between AMTs and the level of human capital for different occupational groups. The results confirm the complementary relationship between human capital and new production technologies. The results by occupational group confirm that to maximise the productivity of new technologies, skilled staff are needed both in management and production, with managers and professionals as well as skilled operatives playing a vital role. Keywords: human capital, process technologies, complementarity, business productivity. (JEL D24, J24, O30).
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The paper assesses the relationship between the use of alternative workplace practices (AWP) and job satisfaction. Using a unique employeremployee data set with rich information on both firm and employee characteristics we test whether there is a positive impact of AWPs on job satisfaction (motivation hypothesis) or it is negative (intensification hypothesis). We expand a growing empirical literature focusing on small and medium size firms from a southern European area. Our results show an overall positive effect, depending on the specific practice considered. We also obtain some sort of time-dependence with the effects turning from negative to positive once the practice has been implemented for some time. Keywords: Job satisfaction, work organization, unobserved heterogeneity.
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Projecte de recerca elaborat a partir d’una estada a la School of politics and international relations, de la University College of Dublin, United Kingdom, entre 2007 i 2009. L’ objectiu del projecte present ha estat contribuir a l’estudi de les negociacions intergovernamentals a la Unió Europea (UE). En primer lloc, s’ha estudiat les estratègies de negociació del estats membres a negociacions intergovernamentals en la UE, per la qual cosa s’ha desenvolupat una tipologia d’estratègies de negociació, diferenciant entre les més agressives (conflictives) i les menys agressives (cooperatives). La conclusió principal ha estat que els actors difereixen en la elecció de les estratègies i que és precisament el poder relatiu dels actors que explica quines estratègies adopten. En segon lloc, s’analitza la ratificació dels resultats a les negociacions intergovernamentals, concentrant-me en l’us dels referèndums. La investigació mostra que els referèndums són sovint usats pels partits polítics com un instrument utilitzat durant les campanyes electorals, posant en dubte la tesis de que l’objectiu principal dels referèndums és influenciar els poder relatiu dels estats membres en negociacions intergovernamentals. Finalment, s’ha estudiat com els actors socials influeixen aquestes negociacions en la UE. La evidencia empírica clarament mostra que la pressió que exerceixen els grups de pressió es sovint subestimada.
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Projecte de recerca elaborat a partir d’una estada a la London School of Economics and Political Science, United Kingdom, entre 2007 i 2009. L’objecte principal del projecte ha estat analitzar les implicacions jurídico-polítiques i institucionals d’una teoria de la justícia i la igualtat liberals aplicada a societats multiculturals amb un marcat predomini de la diversitat cultural. L’anàlisi desenvolupa una línia d'investigació interdisciplinar - entre el dret i la teoria política - iniciada en una tesis doctoral sobre multiculturalisme i drets de les minories culturals (UPF, 2000) que va culminar en la publicació de Group Rights as Human Rights (Springer, 2006). La recerca adopta com a punt de partida les conclusions de l'esmentada obra, en especial, la rellevància del reconeixement de drets col•lectius; tanmateix, el tipus de qüestions plantejades, l’enfoc i la metodologia emprades són substancialment diferents. En concret, s'adrecen preguntes específiques sobre el model i aspiracions del constitucionalisme democràtic i el paper del dret en contextos multiculturals. També s’atorga un pes central a la dimensió institucional dels models de gestió de la diversitat que s’analitzen, prioritzant un enfocament comparatiu a partir de l’estudi de controvèrsies concretes. L’objectiu és superar algunes limitacions importants de la literatura actual, com ara la tendència a examinar en abstracte la compatibilitat de determinades demandes amb el constitucionalisme democràtic, sense abordar el funcionament d'estratègies de gestió de la diversitat cultural emprades en contextos concrets. Els treballs producte d'aquest projecte articulen les línies bàsiques d’un model pluralista, basat en principis més que en regles, que desafia els plantejaments dominants actualment. Aquest model es caracteritza pel compromís amb la legitimitat i igualtat comparatives, rebutjant el paternalisme i les visions liberals típiques sobre el paper de la regulació. La presumpció de l’“standing” moral dels grups identitaris és fonamental per tal de considerar-los interlocutors vàlids amb interessos genuïns. També s’argumenta que la integració social en contextos multiculturals no depèn tant de l’eliminació del conflicte sinó, sobre tot, d’una gestió eficient que eviti abusos de poder sistemàtics. El model defensa el rol del dret en la institucionalització del diàleg intercultural, però admet que el diàleg no necessàriament condueix a l’acord o a una estructura reguladora coherent i uniforme. Les aspiracions del ordre jurídic pluralista són més modestes: afavorir la negociació i resolució en cada conflicte, malgrat la persistència de la fragmentació i la provisionalitat dels acords. La manca d'un marc regulador comú esdevé una virtut en la mesura que permet la interacció de diferents subordres; una interacció governada per una multiplicitat de regles no necessàriament harmòniques. Els avantatges i problemes d’aquest model s'analitzen a partir de l'anàlisi de l’estructura fragmentària de l'ordre jurídic internacional i del règim Europeu de drets humans.
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Des progrès significatifs ont été réalisés dans le domaine de l'intégration quantitative des données géophysique et hydrologique l'échelle locale. Cependant, l'extension à de plus grandes échelles des approches correspondantes constitue encore un défi majeur. Il est néanmoins extrêmement important de relever ce défi pour développer des modèles fiables de flux des eaux souterraines et de transport de contaminant. Pour résoudre ce problème, j'ai développé une technique d'intégration des données hydrogéophysiques basée sur une procédure bayésienne de simulation séquentielle en deux étapes. Cette procédure vise des problèmes à plus grande échelle. L'objectif est de simuler la distribution d'un paramètre hydraulique cible à partir, d'une part, de mesures d'un paramètre géophysique pertinent qui couvrent l'espace de manière exhaustive, mais avec une faible résolution (spatiale) et, d'autre part, de mesures locales de très haute résolution des mêmes paramètres géophysique et hydraulique. Pour cela, mon algorithme lie dans un premier temps les données géophysiques de faible et de haute résolution à travers une procédure de réduction déchelle. Les données géophysiques régionales réduites sont ensuite reliées au champ du paramètre hydraulique à haute résolution. J'illustre d'abord l'application de cette nouvelle approche dintégration des données à une base de données synthétiques réaliste. Celle-ci est constituée de mesures de conductivité hydraulique et électrique de haute résolution réalisées dans les mêmes forages ainsi que destimations des conductivités électriques obtenues à partir de mesures de tomographic de résistivité électrique (ERT) sur l'ensemble de l'espace. Ces dernières mesures ont une faible résolution spatiale. La viabilité globale de cette méthode est testée en effectuant les simulations de flux et de transport au travers du modèle original du champ de conductivité hydraulique ainsi que du modèle simulé. Les simulations sont alors comparées. Les résultats obtenus indiquent que la procédure dintégration des données proposée permet d'obtenir des estimations de la conductivité en adéquation avec la structure à grande échelle ainsi que des predictions fiables des caractéristiques de transports sur des distances de moyenne à grande échelle. Les résultats correspondant au scénario de terrain indiquent que l'approche d'intégration des données nouvellement mise au point est capable d'appréhender correctement les hétérogénéitées à petite échelle aussi bien que les tendances à gande échelle du champ hydraulique prévalent. Les résultats montrent également une flexibilté remarquable et une robustesse de cette nouvelle approche dintégration des données. De ce fait, elle est susceptible d'être appliquée à un large éventail de données géophysiques et hydrologiques, à toutes les gammes déchelles. Dans la deuxième partie de ma thèse, j'évalue en détail la viabilité du réechantillonnage geostatique séquentiel comme mécanisme de proposition pour les méthodes Markov Chain Monte Carlo (MCMC) appliquées à des probmes inverses géophysiques et hydrologiques de grande dimension . L'objectif est de permettre une quantification plus précise et plus réaliste des incertitudes associées aux modèles obtenus. En considérant une série dexemples de tomographic radar puits à puits, j'étudie deux classes de stratégies de rééchantillonnage spatial en considérant leur habilité à générer efficacement et précisément des réalisations de la distribution postérieure bayésienne. Les résultats obtenus montrent que, malgré sa popularité, le réechantillonnage séquentiel est plutôt inefficace à générer des échantillons postérieurs indépendants pour des études de cas synthétiques réalistes, notamment pour le cas assez communs et importants où il existe de fortes corrélations spatiales entre le modèle et les paramètres. Pour résoudre ce problème, j'ai développé un nouvelle approche de perturbation basée sur une déformation progressive. Cette approche est flexible en ce qui concerne le nombre de paramètres du modèle et lintensité de la perturbation. Par rapport au rééchantillonage séquentiel, cette nouvelle approche s'avère être très efficace pour diminuer le nombre requis d'itérations pour générer des échantillons indépendants à partir de la distribution postérieure bayésienne. - Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending corresponding approaches beyond the local scale still represents a major challenge, yet is critically important for the development of reliable groundwater flow and contaminant transport models. To address this issue, I have developed a hydrogeophysical data integration technique based on a two-step Bayesian sequential simulation procedure that is specifically targeted towards larger-scale problems. The objective is to simulate the distribution of a target hydraulic parameter based on spatially exhaustive, but poorly resolved, measurements of a pertinent geophysical parameter and locally highly resolved, but spatially sparse, measurements of the considered geophysical and hydraulic parameters. To this end, my algorithm links the low- and high-resolution geophysical data via a downscaling procedure before relating the downscaled regional-scale geophysical data to the high-resolution hydraulic parameter field. I first illustrate the application of this novel data integration approach to a realistic synthetic database consisting of collocated high-resolution borehole measurements of the hydraulic and electrical conductivities and spatially exhaustive, low-resolution electrical conductivity estimates obtained from electrical resistivity tomography (ERT). The overall viability of this method is tested and verified by performing and comparing flow and transport simulations through the original and simulated hydraulic conductivity fields. The corresponding results indicate that the proposed data integration procedure does indeed allow for obtaining faithful estimates of the larger-scale hydraulic conductivity structure and reliable predictions of the transport characteristics over medium- to regional-scale distances. The approach is then applied to a corresponding field scenario consisting of collocated high- resolution measurements of the electrical conductivity, as measured using a cone penetrometer testing (CPT) system, and the hydraulic conductivity, as estimated from electromagnetic flowmeter and slug test measurements, in combination with spatially exhaustive low-resolution electrical conductivity estimates obtained from surface-based electrical resistivity tomography (ERT). The corresponding results indicate that the newly developed data integration approach is indeed capable of adequately capturing both the small-scale heterogeneity as well as the larger-scale trend of the prevailing hydraulic conductivity field. The results also indicate that this novel data integration approach is remarkably flexible and robust and hence can be expected to be applicable to a wide range of geophysical and hydrological data at all scale ranges. In the second part of my thesis, I evaluate in detail the viability of sequential geostatistical resampling as a proposal mechanism for Markov Chain Monte Carlo (MCMC) methods applied to high-dimensional geophysical and hydrological inverse problems in order to allow for a more accurate and realistic quantification of the uncertainty associated with the thus inferred models. Focusing on a series of pertinent crosshole georadar tomographic examples, I investigated two classes of geostatistical resampling strategies with regard to their ability to efficiently and accurately generate independent realizations from the Bayesian posterior distribution. The corresponding results indicate that, despite its popularity, sequential resampling is rather inefficient at drawing independent posterior samples for realistic synthetic case studies, notably for the practically common and important scenario of pronounced spatial correlation between model parameters. To address this issue, I have developed a new gradual-deformation-based perturbation approach, which is flexible with regard to the number of model parameters as well as the perturbation strength. Compared to sequential resampling, this newly proposed approach was proven to be highly effective in decreasing the number of iterations required for drawing independent samples from the Bayesian posterior distribution.