oalib

时间不限

2017 ( 189 )

2016 ( 744 )

2015 ( 10957 )

2014 ( 14097 )

自定义范围…

匹配条件: “ Daniela S. Krause” ,找到相关结果约330906条。
列表显示的所有文章,均可免费获取
第1页/共330906条
每页显示
Molecular Pathogenesis and Therapy of Polycythemia Induced in Mice by JAK2 V617F
Virginia M. Zaleskas, Daniela S. Krause, Katherine Lazarides, Nihal Patel, Yiguo Hu, Shaoguang Li, Richard A. Van Etten
PLOS ONE , 2006, DOI: 10.1371/journal.pone.0000018
Abstract: Background A somatic activating mutation (V617F) in the JAK2 tyrosine kinase was recently discovered in the majority of patients with polycythemia vera (PV), and some with essential thrombocythemia (ET) and chronic idiopathic myelofibrosis. However, the role of mutant JAK2 in disease pathogenesis is unclear. Methods and Findings We expressed murine JAK2 WT or V617F via retroviral bone marrow transduction/transplantation in the hematopoietic system of two different inbred mouse strains, Balb/c and C57Bl/6 (B6). In both strains, JAK2 V617F, but not JAK2 WT, induced non-fatal polycythemia characterized by increased hematocrit and hemoglobin, reticulocytosis, splenomegaly, low plasma erythropoietin (Epo), and Epo-independent erythroid colonies. JAK2 V617F also induced leukocytosis and neutrophilia that was much more prominent in Balb/c mice than in B6. Platelet counts were not affected in either strain despite expression of JAK2 V617F in megakaryocytes and markedly prolonged tail bleeding times. The polycythemia tended to resolve after several months, coincident with increased spleen and marrow fibrosis, but was resurrected by transplantation to secondary recipients. Using donor mice with mutations in Lyn, Hck, and Fgr, we demonstrated that the polycythemia was independent of Src kinases. Polycythemia and reticulocytosis responded to treatment with imatinib or a JAK2 inhibitor, but were unresponsive to the Src inhibitor dasatinib. Conclusions These findings demonstrate that JAK2 V617F induces Epo-independent expansion of the erythroid lineage in vivo. The fact that the central erythroid features of PV are recapitulated by expression of JAK2 V617F argues that it is the primary and direct cause of human PV. The lack of thrombocytosis suggests that additional events may be required for JAK2 V617F to cause ET, but qualitative platelet abnormalities induced by JAK2 V617F may contribute to the hemostatic complications of PV. Despite the role of Src kinases in Epo signaling, our studies predict that Src inhibitors will be ineffective for therapy of PV. However, we provide proof-of-principle that a JAK2 inhibitor should have therapeutic effects on the polycythemia, and perhaps myelofibrosis and hemostatic abnormalities, suffered by MPD patients carrying the JAK2 V617F mutation.
Neuroinflammation, Microglia and Implications for Anti-Inflammatory Treatment in Alzheimer's Disease
Daniela L. Krause,Norbert Müller
International Journal of Alzheimer's Disease , 2010, DOI: 10.4061/2010/732806
Abstract: Neuroinflammation has been implicated in the pathology of Alzheimer's disease (AD) for decades. Still it has not been fully understood when and how inflammation arises in the course of AD. Whether inflammation is an underling cause or a resulting condition in AD remains unresolved. Mounting evidence indicates that microglial activation contributes to neuronal damage in neurodegenerative diseases. However, also beneficial aspects of microglial activation have been identified. The purpose of this review is to highlight new insights into the detrimental and beneficial role of neuroinflammation in AD. It is our intention to focus on newer controversies in the field of microglia activation. Precisely, we want to shed light on whether neuroinflammation is associated to brain tissue damage and functional impairment or is there also a damage limiting activity. In regard to this, we discuss the limitations and the advantages of anti-inflammatory treatment options and identify what future implications might result from this underling neuroinflammation for AD therapy. 1. Introduction The pathology of Alzheimer’s disease (AD) is characterized by the deposition of amyloid- (A ) plaques in the brain parenchyma and neurofibrillary tangles within neurons [1]. Apart from the disease's distinct pathological markers, its neurodegenerative conditions are characterized by chronic neuroinflammatory processes. Yet, those inflammatory markers are not exclusively associated with AD. Also brains of “healthy aged” individuals show concentrations of serum markers related to inflammation, homocysteine and cholesterol homeostasis are associated with cognitive functioning in the nondemented healthy aging population [2]. In the AD pathology, these aging-related inflammatory processes are increased. The suggestion that inflammation may participate in AD first came up more than two decades ago. As several clinical trials have shown a beneficial effect for nonsteroidal anti-inflammatory drugs for the occurrence and course of AD, the inflammatory hypothesis in AD gained a lot of attention. In regard to treatment and prevention of AD, several classes of medications have emerged to the market, which improve the cognitive symptoms of this disorder (e.g. the cholinesterase inhibitors). But the relief that these drugs provide remains symptomatic—so it is a major goal for the future to develop effective disease-modifying therapy. Different substantial efforts have been made to identify potential strategies to ameliorate or prevent AD pathology, with data stemming from basic research as well as
An advanced approach for catchment delineation and water balance modelling within wetlands and floodplains
S. Krause,A. Bronstert
Advances in Geosciences (ADGEO) , 2005,
Abstract: Water balance of wetlands within lowland floodplains is strongly influenced by the temporally variable spatial extent of the interactions between groundwater and surface water. A robust algorithm will be introduced which makes it possible to delineate the interaction zone between the lowland river and the floodplain. This interaction zone is specified as the "Direct Catchment" which is defined by the part of the connected floodplain in which wetland water balance is mainly affected by the surface water dynamics of the adjacent river. The delineation algorithm is based on transfer functions which were assessed by local simulation results of the integrated water balance and nutrient dynamics model IWAN. The transfer functions are further determined by mean annual groundwater depths and by simulated groundwater dynamics. They are controlled by simulation results of the maximal transversal extent of surface water influence on groundwater stages. The regionalisation of the developed delineation algorithm leads to the specification of the maximal extent of groundwater - surface water - interaction processes along the river. By application of this approach to the Havel River basin, located within lowlands of Northeaster Germany, it was possible to specify a 998.1 km2 part of the floodplain which is directly connected with the surface waters and thus called the "Direct Catchment" of the Havel river. The IWAN model was applied to simulate the water balance of the floodplain. The simulation results prove the tight interaction between river and floodplain. It is shown that the spatially and temporally variable influences of the connected floodplain on the river discharge were only important during low discharge in summer.
Simulation and analysis of the impact of projected climate change on the spatially distributed waterbalance in Thuringia, Germany
P. Krause ,S. Hanisch
Advances in Geosciences (ADGEO) , 2009,
Abstract: The impact of projected climate change on the long-term hydrological balance and seasonal variability in the federal German state of Thuringia was assessed and analysed. For this study projected climate data for the scenarios A2 and B1 were used in conjunction with a conceptual hydrological model. The downscaled climate data are based on outputs of the general circulation model ECHAM5 and provide synthetic climate time series for a large number of precipitation and climate stations in Germany for the time period of 1971 to 2100. These data were used to compute the spatially distributed hydrological quantities, i.e. precipitation, actual evapotranspiration and runoff generation with a conceptual hydrological model. This paper discusses briefly the statistical downscaling method and its validation in Thuringia and includes an overview of the hydrological model. The achieved results show that the projected climate conditions in Thuringia follow the general European climate trends – increased temperature, wetter winters, drier summers. But, in terms of the spatial distribution and interannual variability regional differences occur. The analysis showed that the general increase of the winter precipitation is more distinct in the mid-mountain region and less pronounced in the lowland whereas the decrease of summer precipitation is higher in the lowland and less distinct in the mid-mountains. The actual evapotranspiration showed a statewide increase due to higher temperatures which is largest in the summer period. The resulting runoff generation in winter was found to increase in the mid-mountains and to slightly decrease in the lowland region. In summer and fall a decrease in runoff generation was estimated for the entire area due to lower precipitation and higher evapotranspiration rates. These spatially differentiated results emphasize the need of high resolution climate input data and distributed modelling for regional impact analyses.
Uptake of genetic counselling services by patients with cystic fibrosis and their families
S Macaulay, A Krause
South African Family Practice , 2012,
Abstract: Background: Although cystic fibrosis (CF) is a common genetic condition, genetic counselling services appear to be underutilised by affected families. The aim of this study was to determine the uptake of genetic counselling and mutation testing for CF by relatives of affected individuals, and the impact of introducing hospital-based genetic counselling services. Method: The files of 153 families seen for genetic counselling for CF by staff of the Division of Human Genetics, School of Pathology, University of the Witwatersrand, and the National Health Laboratory Service (NHLS) in Johannesburg, were retrospectively reviewed from 1990 to 2006, the year when hospital-based genetic counselling services were introduced. Results: Parents of CF probands were the largest single group (35%) of counsellees. Most individuals (66%) attended genetic counselling to gather information. Most had been referred by medical specialists (56%). Only 10% of referrals originated from general practitioners. On average, from 1990-2005, six families received genetic counselling annually, whereas in 2006, 58 families were seen. In 140 unrelated families, 1 991 relatives with carrier risks of . 25% were identified. Only 11% of these relatives underwent mutation testing, and eight per cent received genetic counselling through our division over the review period. Conclusion: Overall, referrals of family members (of affected CF individuals) to genetic counselling, by general practitioners, are poor. Uptake of genetic counselling services is greater when such services are integrated into hospital-based CF management clinics, than when offered elsewhere. The low uptake of mutation testing and genetic counselling by at-risk relatives is a concern, since these relatives are at high risk of having affected children, if their partners are CF carriers. Education of affected individuals, their close relatives, and medical practitioners, should be prioritised. This will ensure referral to genetic counselling for discussion about the risks of and available testing for CF, and other genetic conditions.
Prognostic simulation and analysis of the impact of climate change on the hydrological dynamics in Thuringia, Germany
P. Krause,S. Hanisch
Hydrology and Earth System Sciences Discussions , 2007,
Abstract: The impact of predicted climate change on the hydrological dynamics and long term hydrological balance in the federal German state Thuringia was investigated and analysed. For this study the prognostic climate data, provided by the statistical regionalisation approach WETTREG, which is based on results of the global climate model ECHAM5/MPI-OM, was used. This regional climate model provides synthetic climate time series for the existent precipitation and climate station in Germany from 2000 to 2100. This data was processed with the hydrological model J2000g which we used for the regionalisation of the climatological time series data and for the computation of potential and actual evapotranspiration, runoff generation and groundwater recharge. In this study we analysed the two emission scenarios A2 and B1, defined by the Intergovernmental Panel on Climate Change (IPCC) and their impact on the temporal and spatial distribution of temperature, precipitation, evapotranspiration and runoff generation for the time frame 2071–2100 for the entire area of the German state of Thuringia. For this purpose we compared simulation with the scenario data with simulation results based on reference data from 1971–2000. The comparison showed an increase of the mean annual temperature of 1.8 (B1) to 2.2 (A2) °C which is much more distinct during winter. The mean annual precipitation is decreasing only slightly but, the seasonal spatio-temporal rainfall distribution which has major impact on the hydrological water balance is changing significantly. This pattern change results in more precipitation during winter and less in summer. Actual evapotranspiration was computed higher for both scenarios compared to the evapotranspiration of the reference period 1971–2000. As a follow up a decrease in the runoff generation was simulated which was again very variable in space and time. The overall trends worked out in this study showed that it is likely that the extremes of flooding in winter and dry spells in summer might occur more often in Thuringia because of the changing weather conditions due to climate change.
Infectious agents are associated with psychiatric diseases
Daniela Lydia Krause,Elif Weidinger,Judith Matz,Agnes Wildenauer
Mental Illness , 2012, DOI: 10.4081/mi.2012.e10
Abstract: There are several infectious agents in the environment that can cause persistent infections in the host. They usually cause their symptoms shortly after first infection and later persist as silent viruses and bacteria within the body. However, these chronic infections may play an important role in the pathogenesis of schizophrenia and Tourette’s syndrome (TS). We investigated the distribution of different neurotrophic infectious agents in TS, schizophrenia and controls. A total of 93 individuals were included (schizophrenic patients, Tourette patients and controls). We evaluated antibodies against cytomegalovirus (CMV), herpes-simplex virus (HSV), Epstein-Barr virus, Toxoplasma, Mycoplasma and Chlamydia trachomatis/pneumoniae. By comparing schizophrenia and TS, we found a higher prevalence of HSV (P=0.017) and CMV (P=0.017) antibodies in schizophrenic patients. Considering the relationship between schizophrenia, TS and healthy controls, we showed that there are associations for Chlamydia trachomatis (P=0.007), HSV (P=0.027) and CMV (P=0.029). When all measured viruses, bacteria and protozoa were combined, schizophrenic patients had a higher rate of antibodies to infectious agents than TS patients (P=0.049). Tourette and schizophrenic patients show a different vulnerability to infectious agents. Schizophrenic patients were found to have a higher susceptibility to viral infections than individuals with TS. This finding might point to a modification in special immune parameters in these diseases.
Towards an Open Modelling Interface (OpenMI) the HarmonIT project
S. Kralisch, P. Krause,O. David
Advances in Geosciences (ADGEO) , 2005,
Abstract: State of the art challenges in sustainable management of water resources have created demand for integrated, flexible and easy to use hydrological models which are able to simulate the quantitative and qualitative aspects of the hydrological cycle with a sufficient degree of certainty. Existing models which have been de-veloped to fit these needs are often constrained to specific scales or purposes and thus can not be easily adapted to meet different challenges. As a solution for flexible and modularised model development and application, the Object Modeling System (OMS) has been developed in a joint approach by the USDA-ARS, GPSRU (Fort Collins, CO, USA), USGS (Denver, CO, USA), and the FSU (Jena, Germany). The OMS provides a modern modelling framework which allows the implementation of single process components to be compiled and applied as custom tailored model assemblies. This paper describes basic principles of the OMS and its main components and explains in more detail how the problems during coupling of models or model components are solved inside the system. It highlights the integration of different spatial and temporal scales by their representation as spatial modelling entities embedded into time compound components. As an exam-ple the implementation of the hydrological model J2000 is discussed.
Inverse distributed hydrological modelling of Alpine catchments
H. Kunstmann, J. Krause,S. Mayr
Hydrology and Earth System Sciences (HESS) & Discussions (HESSD) , 2006,
Abstract: Even in physically based distributed hydrological models, various remaining parameters must be estimated for each sub-catchment. This can involve tremendous effort, especially when the number of sub-catchments is large and the applied hydrological model is computationally expensive. Automatic parameter estimation tools can significantly facilitate the calibration process. Hence, we combined the nonlinear parameter estimation tool PEST with the distributed hydrological model WaSiM. PEST is based on the Gauss-Marquardt-Levenberg method, a gradient-based nonlinear parameter estimation algorithm. WaSiM is a fully distributed hydrological model using physically based algorithms for most of the process descriptions. WaSiM was applied to the alpine/prealpine Ammer River catchment (southern Germany, 710 km2 in a 100×100 m2 horizontal resolution. The catchment is heterogeneous in terms of geology, pedology and land use and shows a complex orography (the difference of elevation is around 1600 m). Using the developed PEST-WaSiM interface, the hydrological model was calibrated by comparing simulated and observed runoff at eight gauges for the hydrologic year 1997 and validated for the hydrologic year 1993. For each sub-catchment four parameters had to be calibrated: the recession constants of direct runoff and interflow, the drainage density, and the hydraulic conductivity of the uppermost aquifer. Additionally, five snowmelt specific parameters were adjusted for the entire catchment. Altogether, 37 parameters had to be calibrated. Additional a priori information (e.g. from flood hydrograph analysis) narrowed the parameter space of the solutions and improved the non-uniqueness of the fitted values. A reasonable quality of fit was achieved. Discrepancies between modelled and observed runoff were also due to the small number of meteorological stations and corresponding interpolation artefacts in the orographically complex terrain. Application of a 2-dimensional numerical groundwater model partly yielded a slight decrease of overall model performance when compared to a simple conceptual groundwater approach. Increased model complexity therefore did not yield in general increased model performance. A detailed covariance analysis was performed allowing to derive confidence bounds for all estimated parameters. The correlation between the estimated parameters was in most cases negligible, showing that parameters were estimated independently from each other. Final Revised Paper (PDF, 6591 KB) Discussion Paper (HESSD) Citation: Kunstmann, H., Krause, J., and Mayr, S.: Inverse distributed hydrological modelling of Alpine catchments, Hydrol. Earth Syst. Sci., 10, 395-412, doi:10.5194/hess-10-395-2006, 2006. Bibtex EndNote Reference Manager XML
Investigating patterns and controls of groundwater up-welling in a lowland river by combining Fibre-optic Distributed Temperature Sensing with observations of vertical hydraulic gradients
S. Krause, T. Blume,N. J. Cassidy
Hydrology and Earth System Sciences (HESS) & Discussions (HESSD) , 2012,
Abstract: This paper investigates the patterns and controls of aquifer–river exchange in a fast-flowing lowland river by the conjunctive use of streambed temperature anomalies identified with Fibre-optic Distributed Temperature Sensing (FO-DTS) and observations of vertical hydraulic gradients (VHG). FO-DTS temperature traces along this lowland river reach reveal discrete patterns with "cold spots" indicating groundwater up-welling. In contrast to previous studies using FO-DTS for investigation of groundwater–surface water exchange, the fibre-optic cable in this study was buried in the streambed sediments, ensuring clear signals despite fast flow and high discharges. During the observed summer baseflow period, streambed temperatures in groundwater up-welling locations were found to be up to 1.5 °C lower than ambient streambed temperatures. Due to the high river flows, the cold spots were sharp and distinctly localized without measurable impact on down-stream surface water temperature. VHG patterns along the stream reach were highly variable in space, revealing strong differences even at small scales. VHG patterns alone are indicators of both, structural heterogeneity of the stream bed as well as of the spatial heterogeneity of the groundwater–surface water exchange fluxes and are thus not conclusive in their interpretation. However, in combination with the high spatial resolution FO-DTS data we were able to separate these two influences and clearly identify locations of enhanced exchange, while also obtaining information on the complex small-scale streambed transmissivity patterns responsible for the very discrete exchange patterns. The validation of the combined VHG and FO-DTS approach provides an effective strategy for analysing drivers and controls of groundwater–surface water exchange, with implications for the quantification of biogeochemical cycling and contaminant transport at aquifer–river interfaces.
第1页/共330906条
每页显示


Home
Copyright © 2008-2017 jourlib.org. All rights reserved.