Thomas Reimann

Transforming growth factor-β1 induces activation of Ras, Raf-1, MEK and MAPK in rat hepatic stellate cells

© 1997 Federation of European Biochemical Societies.

Loss of caveolin expression in type I pneumocytes as an indicator of subcellular alterations during lung fibrogenesis

Abstract Caveolin is a major structural protein of caveolae, also known as plasmalemmal vesicles, which are particularly abundant in type I pneumocytes and capillary endothelial cells of lung parenchyma. Here we demonstrate that caveolin expression in the alveolar epithelium of rats and mini pigs is strikingly downregulated after irradiation-induced lung injury. Indirect immunoperoxidase staining with polyclonal anti-caveolin antibodies, confirmed by double fluorescence studies with type I cell-specific monoclonal anti-cytokeratin antibodies or lectins, revealed a dramatic loss of caveolin immunoreactivity in type I pneumocytes. In contrast, caveolin expression increased in endothelial cells. Immunoblotting of lung homogenates from normal and irradiated rats using specific anti-caveolin antibodies confirmed the presence of caveolin in normal tissue and its marked decrease of expression in fibrotic tissue. The loss of caveolin as an important structural protein of caveolae in alveolar epithelial cells may be an early indicator of serious type I cell injury during fibrogenesis. The increase of caveolin immunoreactivity in endothelia of blood vessels may indicate that different types of caveolae and/or different regulatory mechanisms of caveolin expression exist.

Upregulation of gap junction protein connexin43 in alveolar epithelial cells of rats with radiation-induced pulmonary fibrosis

The degree of immunoreactive connexin43 (Cx43) in rat lung was evaluated during the development of radiation-induced pulmonary fibrosis in rat by a double immunofluorescence technique using polyclonal antisera of Cx43 and monoclonal antibodies to cytokeratins on cryostat sections. In normal rat lungs, Cx43 was detected in pneumocytes type II and I, in large blood vessel endothelia, in peribronchial smooth muscle cells, and in some peribronchial and perivascular interstitial cells. As early as 1 week after irradiation, enhanced immunoreactivity for Cx43 in the epithelial cells was detected. In severely injured lungs (about 3 months after irradiation), Cx43 was found also in the cytoplasm of type II pneumocytes. These findings were confirmed by western blot data. Western blot analysis also revealed increased phosphorylation of Cx43. It remains to be investigated whether the increased content of Cx43 in irradiated rat lung may be due to an enhanced number of gap junction between type I and II alveolar epithelial cells.

Differentiated characterization of karst aquifers: some contributions

Because of the small radius of investigation of hydrogeological standard testing methods, the characterization of karst aquifers is still a challenge. The development of a karst conduit system introduces an element of large contrast in hydraulic conductivity in the hydraulic parameter field of a karst aquifer. It leads to complex flow patterns and transport phenomena that differ significantly from those observed in porous and fissured media. While on a local, i.e., borehole scale, the fissured matrix of karst aquifers can be regarded as a continuum, on a regional, i.e., catchment scale, the drainage of the aquifer system is controlled by the conduit system, which may have a highly anisotropic geometry. Therefore, characterization of karst aquifers requires a differentiated approach by the combination of various hydrogeological field methods or the application of large-scale tests, which cover the scale of dominant aquifer heterogeneities. Existing numerical modeling approaches can be applied for integral data interpretation on catchment scale.

Modifications to the Conduit Flow Process Mode 2 for MODFLOW-2005.

As a result of rock dissolution processes, karst aquifers exhibit highly conductive features such as caves and conduits. Within these structures, groundwater flow can become turbulent and therefore be described by nonlinear gradient functions. Some numerical groundwater flow models explicitly account for pipe hydraulics by coupling the continuum model with a pipe network that represents the conduit system. In contrast, the Conduit Flow Process Mode 2 (CFPM2) for MODFLOW-2005 approximates turbulent flow by reducing the hydraulic conductivity within the existing linear head gradient of the MODFLOW continuum model. This approach reduces the practical as well as numerical efforts for simulating turbulence. The original formulation was for large pore aquifers where the onset of turbulence is at low Reynolds numbers (1 to 100) and not for conduits or pipes. In addition, the existing code requires multiple time steps for convergence due to iterative adjustment of the hydraulic conductivity. Modifications to the existing CFPM2 were made by implementing a generalized power function with a user-defined exponent. This allows for matching turbulence in porous media or pipes and eliminates the time steps required for iterative adjustment of hydraulic conductivity. The modified CFPM2 successfully replicated simple benchmark test problems.

Application of the flow dimension concept for numerical drawdown data analyses in mixed-flow karst systems

A numerical discrete conduit-continuum model is employed to investigate large-scale groundwater abstraction in karst aquifers. The application of large-scale experiments is one approach to deal with the scale problem in hydraulic parameter assessment, caused by significant contrasts of hydraulic parameters in a karst aquifer. Here, conduit drawdown is evaluated by diagnostic plots and by considering the apparent flow dimension. These tools are frequently used for the interpretation of hydraulic borehole tests by analytical solutions. In contrast to existing analytical solutions, a numerical groundwater model allows the incorporation of the effect of complex parameter distributions. The objective is to demonstrate the application of diagnostic plots and flow dimension analysis for a systematic analysis of the effect of different boundary conditions as well as sink/source terms for idealized two-dimensional mixed karst aquifer systems, which ultimately extends existing analytical solutions and, therefore, contributes to the interpretation of measured field data. The analysis is focused on the apparent flow dimension and shows the extension of the cross-sectional flow area for selected models. The results are used to evaluate the large-scale pumping test of the karstified Cent Fonts catchment (Languedoc, France). The inverse calibration of two realistic, but still simplified, catchment models reveals that the apparent flow dimension supplies useful information about the general flow pattern during the Cent Fonts pumping test. The flow dimension after the end of the storage period can be explained by a large contribution of exchange flow resulting in a strong influence of radial flow on regional, i.e., kilometer scale.RésuméUn modèle numérique à conduit discrétisé au sein d’un continuum est utilisé pour étudier les prélèvements d’eaux souterraines à grande échelle dans les aquifères karstiques. La réalisation d’expériences à grande échelle est une approche pour traiter le problème d’échelle dans l’évaluation des paramètres hydrauliques, hétérogènes suite aux contrastes importants dans un aquifère karstique. Dans ce cas, le rabattement dans le conduit est évalué à l’aide de graphiques de diagnostic et en considérant la dimension de l’écoulement apparent. Ces outils sont fréquemment utilisés pour l’interprétation des tests hydrauliques en forage à l’aide de solutions analytiques. Contrairement aux solutions analytiques existantes, un modèle numérique d’écoulement d’eaux souterraines permet d’introduire l’effet de la distribution spatiale complexe des paramètres. L’objectif est de démontrer l’application des graphiques de diagnostic et d’analyse de la dimension de l’écoulement pour une analyse systématique de l’effet de différentes conditions aux limites ainsi que des termes source pour des/source pour des systèmes karstiques mixtes idéalisés bidimensionnel, qui permettent d’étendre en fin de compte les solutions analytiques existantes et, par conséquence, contribuer à l’interprétation des données de terrain. L’analyse se concentre sur la dimension de l’écoulement apparent et montre l’extension de la section transversale d’écoulement pour les modèles sélectionnés. Les résultats sont utilisés pour évaluer l’essai de pompage à grande échelle du système karstique des Cent Fonts (Languedoc, France). La calibration inverse de deux modèles réalistes, mais encore simplifiés, révèle que la dimension de l’écoulement apparent fournit des informations utiles concernant le mode d’écoulement général au cours de l’essai de pompage des Cent Fonts. La dimension de l’écoulement après la fin de la période de stockage peut être expliquée par une contribution importante d’écoulement échangé résultant d’une forte influence de l’écoulement radial à l’échelle régionale, c’est-à-dire kilométriqueResumenSe emplea un modelo numérico de conducto-continuo discreto para investigar la extracción de agua subterránea a gran escala en acuíferos kársticos. La aplicación de experimentos a gran escala es un enfoque para tratar el problema de escala en la evaluación de parámetros hidráulicos, causado por contrastes significativos en los parámetros hidráulicos en un acuífero kárstico. En este caso, la extracción del conducto se evalúa mediante parcelas de diagnóstico y considerando la dimensión aparente de flujo. Estas herramientas se utilizan frecuentemente para la interpretación de ensayos hidráulicos de pozos mediante soluciones analíticas. A diferencia de las soluciones analíticas existentes, un modelo numérico de agua subterránea permite la incorporación del efecto de distribuciones de parámetros complejos. El objetivo es demostrar la aplicación de parcelas diagnósticas y el análisis dimensional de flujo para un análisis sistemático del efecto de diferentes condiciones de borde así como términos de sumidero/fuente para sistemas idealizados de acuíferos kársticos mixtos bidimensionales, lo que extiende en última instancia las soluciones analíticas existentes y por lo tanto, contribuye a la interpretación de los datos de campo medidos. El análisis se centra en la dimensión de flujo aparente y muestra la extensión del área de flujo transversal para los modelos seleccionados. Los resultados se usan para evaluar los ensayos de bombeo a gran escala de la cuenca kárstica de Cent Fonts (Languedoc, Francia). La calibración inversa de dos modelos realísticos de captación, pero aún simplificados, revela que la dimensión de flujo aparente proporciona información útil sobre el patrón de flujo general durante los ensayos de bombeo de Cent Fonts. La dimensión de flujo después del final del período de almacenamiento puede explicarse por una gran contribución del flujo de intercambio que da como resultado una fuerte influencia del flujo radial en una escala regional, es decir, en una escala de kilómetros.摘要采用数值离散通道-连续模型研究岩溶含水层大规模的地下水开采。应用大规模的实验是处理岩溶含水层水力参数重大差别导致的水力参数评价中尺度问题的一种方法。这里,通过诊断图和明显的流维评价了通道水位下降。通过解析解,这些工具常常用于水力钻孔试验的解译。与现有的解析解形成对比,数值地下水模型可以合并复杂参数分布的影响。目的就是展示诊断图和流维分析在不同边界条件影响和汇/源项的系统分析中的应用,理想化二维混合的岩溶含水层系统,这个系统分析最终扩充现有的解析解,从而有助于测量的野外资料的解译。分析集中在明显的流维,显示存在着所选模型截面流面积的扩展。结果用于评价(法国朗格多克省)岩溶化的Cent Fonts流域的大规模抽水试验。两个现实的、但仍然是简化的流域模型的逆校准揭示,在抽水试验期间,明显的流维在有关总的流动形态方面提供了有用的信息。蓄水期终结之后的流维可由大量的交换流解释,大量的交换流导致区域尺度上也就是公里尺度上径向流的强烈影响。.ResumoUm modelo numérico discreto do tipo conduto-contínuo é empregado para investigar a retirada de águas subterrâneas em larga escala em aquíferos cársticos. A aplicação de experimentos de larga escala é uma abordagem para lidar com o problema de escala na avaliação de parâmetros hidráulicos, causado pelos contrastes significativos dos parâmetros hidráulicos em um aquífero cárstico. Aqui, o rebaixamento do conduto é avaliado por meio de gráficos de diagnóstico e considerando a dimensão de escoamento aparente. Essas ferramentas são frequentemente usadas para a interpretação de testes hidráulicos de poços por meio de soluções analíticas. Em contraste com as soluções analíticas existentes, um modelo numérico de águas subterrâneas permite a incorporação do efeito das distribuições de parâmetros complexos. O objetivo é demonstrar a aplicação de gráficos de diagnósticos e do escoamento dimensional para uma análise sistemática dos efeitos de diferentes condições de contorno, bem como os termos de sumidouros/fontes para os sistemas aquíferos cársticos mistos e bidimensionais idealizados, os quais em última instância, incorporam as soluções analíticas existentes e, portanto, contribuem para a interpretação dos dados de campo medidos. A análise é focada na dimensão aparente de escoamento e mostra a extensão da área de escoamento transversal para os modelos selecionados. Os resultados são usados para avaliar testes de bombeamento da bacia carstificada Cent Fonts (Languedoc, França). A calibração inversa de dois modelos de bacias realísticos, porém simplificados, relevam que a dimensão aparente do escoamento fornece informações úteis sobre o padrão geral de escoamento durante os testes de bombeamento em Cent Fonts. A dimensão de escoamento após o término do período de armazenamento pode ser explicada pela ampla contribuição da troca de escoamento, resultando em uma forte influência do escoamento radial regional, por exemplo, na escala de quilômetros.

Turbulent and Laminar Flow in Karst Conduits Under Unsteady Flow Conditions: Interpretation of Pumping Tests by Discrete Conduit-Continuum Modeling

Due to the duality in terms of (1) the groundwater flow field and (2) the discharge conditions, flow patterns of karst aquifer systems are complex. Estimated aquifer parameters may differ by several orders of magnitude from local (borehole) to regional (catchment) scale because of the large contrast in hydraulic parameters between matrix and conduit, their heterogeneity and anisotropy. One approach to deal with the scale effect problem in the estimation of hydraulic parameters of karst aquifers is the application of large-scale experiments such as long-term high-abstraction conduit pumping tests, stimulating measurable groundwater drawdown in both, the karst conduit system as well as the fractured matrix. The numerical discrete conduit-continuum modeling approach MODFLOW-2005 Conduit Flow Process Mode 1 (CFPM1) is employed to simulate laminar and nonlaminar conduit flow, induced by large-scale experiments, in combination with Darcian matrix flow. Effects of large-scale experiments were simulated for idealized settings. Subsequently, diagnostic plots and analyses of different fluxes are applied to interpret differences in the simulated conduit drawdown and general flow patterns. The main focus is set on the question to which extent different conduit flow regimes will affect the drawdown in conduit and matrix depending on the hydraulic properties of the conduit system, i.e., conduit diameter and relative roughness. In this context, CFPM1 is applied to investigate the importance of considering turbulent conditions for the simulation of karst conduit flow. This work quantifies the relative error that results from assuming laminar conduit flow for the interpretation of a synthetic large-scale pumping test in karst.

Inverse Parametrization of a Regional Groundwater Flow Model with the Aid of Modelling and GIS: Test and Application of Different Approaches

The use of inverse methods allow efficient model calibration. This study employs PEST to calibrate a large catchment scale transient flow model. Results are demonstrated by comparing manually calibrated approaches with the automated approach. An advanced Tikhonov regularization algorithm was employed for carrying out the automated pilot point (PP) method. The results indicate that automated PP is more flexible and robust as compared to other approaches. Different statistical indicators show that this method yields reliable calibration as values of coefficient of determination (R2) range from 0.98 to 0.99, Nash Sutcliffe efficiency (ME) range from 0.964 to 0.976, and root mean square errors (RMSE) range from 1.68 m to 1.23 m, for manual and automated approaches, respectively. Validation results of automated PP show ME as 0.969 and RMSE as 1.31 m. The results of output sensitivity suggest that hydraulic conductivity is a more influential parameter. Considering the limitations of the current study, it is recommended to perform global sensitivity and linear uncertainty analysis for the better estimation of the modelling results.