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Berlin Brandenburg

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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 07 January 2014, Vol.111(1), pp.409-14
    Description: A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.
    Keywords: Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Antineoplastic Agents, Alkylating -- Pharmacology ; Brain Neoplasms -- Drug Therapy ; Cell Cycle Proteins -- Metabolism ; Glioblastoma -- Drug Therapy ; Glioma -- Drug Therapy ; Intracellular Signaling Peptides and Proteins -- Metabolism ; O(6)-Methylguanine-DNA Methyltransferase -- Pharmacology ; Tor Serine-Threonine Kinases -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    In: Geophysical Research Letters, February 2011, Vol.38(3), pp.n/a-n/a
    Description: Due to temperature differences of groundwater and streamwater, localized groundwater inflows into small streams can directly be detected with ground‐based thermographic systems in summer or winter. Infrared radiation temperatures of surface water were used to determine mixing length and to calculate the relative fraction of groundwater inflow to downstream discharge. These fractions were comparable to groundwater inflow fractions derived from electrical conductivity, kinetic water temperatures and discharge measurements. This approach advances the immediate detection and quantification of localized groundwater inflow for hydrology, geology and ecology.
    Keywords: Groundwater‐Surface Water Interaction ; Water Temperature ; Infrared Thermography
    ISSN: 0094-8276
    E-ISSN: 1944-8007
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  • 3
    Language: English
    In: Journal of Hydrology, 2005, Vol.310(1), pp.294-315
    Description: Simulating infiltration in soils containing macropores still provides unsatisfactory results, as existing models seem not to capture all relevant processes. Recent studies of macropore flow initiation in natural soils containing earthworm channels revealed a distinct flow rate variability in the macropores depending on the initiation process. When macropore flow was initiated at the soil surface, most of the macropores received very little water while a few macropores received a large proportion of the total inflow. In contrast, when macropore flow was initiated from a saturated or nearly saturated soil layer, macropore flow rate variation was much lower. The objective of this study was to develop, evaluate, and test a model, which combines macropore flow variability with several established approaches to model dual permeability soils. We then evaluate the INfiltration–INitiation–INteraction Model (IN M) to explore the influence of macropore flow variability on infiltration behavior by performing a sensitivity analysis and applying IN M to sprinkling and dye tracer experiments at three field sites with different macropore and soil matrix properties. The sensitivity analysis showed that the flow variability in macropores reduces interaction between the macropores and the surrounding soil matrix and thus increases bypass flow, especially for surface initiation of macropore flow and at higher rainfall intensities. The model application shows reasonable agreement between IN M simulations and field data in terms of water balance, water content change, and dye patterns. The influence of macropore flow variability on the hydrological response of the soil was considerable and especially pronounced for soils where initiation occurs at the soil surface. In future, the model could be applied to explore other types of preferential flow and hence to get a generally better understanding of macropore flow.
    Keywords: Macropore Flow ; Infiltration ; Soil Moisture ; Unsaturated Zone ; Dual-Permeability Model ; Earthworm Burrow ; Geography
    ISSN: 0022-1694
    E-ISSN: 1879-2707
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  • 4
    In: Hydrological Processes, 01 January 2017, Vol.31(1), pp.15-19
    Description: Preferential flow is of high relevance for runoff generation, transport of chemicals and nutrients, and the transit time distribution of water in the soil or watershed. However, preferential flow effects are generally ignored in lumped hydrological models. And even most physically‐based models ignore macropores and preferential flow features at the soil and hillslope scale. Keith Beven was never satisfied with this situation and he tried again and again to convince the scientific community to focus their research on the complex topic of macropore and preferential flow. Although he recognized how difficult it is to correctly include preferential flow in hydrological models, he made substantial progress defining and describing macropore flow and showing its relevance, developing models to simulate preferential flow, and in particular, the interaction between macropores and the soil matrix. In this short commentary, I reflect on these achievements and outline a vision for research in preferential flow experiments and modeling.
    Keywords: Infiltration ; Macropore Flow ; Preferential Flow ; Runoff Generation
    ISSN: 0885-6087
    E-ISSN: 1099-1085
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  • 5
    Language: English
    In: Journal of Hydrology, 2011, Vol.396(3), pp.277-291
    Description: ► Specification of spatially distributed lateral fluxes affects solute transport parameter estimates. ► Information contained on the breakthrough curve alone is insufficient to select the appropriate model structure. ► Implementation of , the lateral ouflow, in OTIS leads to solute mass to groundwater. ► The absence of implementation of in OTIS promotes the storage of solute mass in the transient storage zone. Interactions between mobile stream water and transient storage zones have been the subject of careful attention for decades. However, few studies have considered explicitly the influence of water exchange between the channel and neighbouring hydrological units when modelling transient storage processes, especially the lateral inflow coming from hillslope contributions and outflow to a deep aquifer or to hyporheic flow paths extending beyond the study reach. The objective of this study was to explore the influence of different conceptualizations of these hydrologic exchanges on the estimation of transient storage parameters. Slug injections of sodium chloride (NaCl) were carried out in eight contiguous reaches in the Cotton Creek Experimental Watershed (CCEW), located in south-east British Columbia. Resulting breakthrough curves were subsequently analysed using a Transient Storage Model (TSM) in an inverse modelling framework. We estimated solute transport parameters using three distinct, hypothetical spatial patterns of lateral inflow and outflow, all based on variations of the same five-parameter model structure. We compared optimized parameter values to those resulting from a distinct four-parameter model structure meant to represent the standard application of the TSM, in which only lateral inflow was implemented for net gaining reaches or only lateral outflow for net losing reaches. In the five-parameter model, solute mass was stored predominantly in the transient storage zone and slowly released back to the stream. Conversely, solute mass was predominantly removed from the stream via flow losses in the four-parameter model structure. This led to contrasting estimates of solute transport parameters and subsequent interpretation of solute transport dynamics. Differences in parameter estimates across variations of the five-parameter model structure were small yet statistically significant, except for the transient storage exchange rate coefficient , for which unique determination was problematic. We also based our analysis on , the fraction of median transport time due to transient storage. Differences across configurations in estimates were consistent but small when compared to the variability of among reaches. Optimized parameter values were influenced dominantly by the model structure (four versus five parameters) and then by the conceptualization of spatial arrangement of lateral fluxes along the reach for a set model structure. When boundary conditions are poorly defined, the information contained in the stream tracer breakthrough curve is insufficient to identify a single, unambiguous model structure representing solute transport simulations. Investigating lateral fluxes prior to conducting a study on transient storage processes is necessary, as assuming a certain spatial organization of these fluxes might set ill-defined bases for inter-reach comparisons. Given the difficulty in quantifying the spatial patterns and magnitudes of lateral inputs and outputs, we recommend small-scale laboratory tracer experiments with well-defined and variable boundary conditions as a complement to field studies to provide new insights into stream solute dynamics.
    Keywords: Transient Storage ; Flow Loss ; Flow Gain ; Otis ; Uncertainty ; Model Structure ; Geography
    ISSN: 0022-1694
    E-ISSN: 1879-2707
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  • 6
    In: Chemical Communications, 2014, Vol.50(97), pp.15419-15422
    Description: A chemical route to periodic hole arrays in gold films whose holes are loaded with single gold nanoparticles is presented, paving the road to mass production of highly sensitive plasmonic sensors on large areas.
    Keywords: Nanopores ; Gold -- Chemistry ; Metal Nanoparticles -- Chemistry ; Surface Plasmon Resonance -- Instrumentation;
    ISSN: 1359-7345
    E-ISSN: 1364-548X
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(4), p.e0122539
    Description: Soil microbial communities play an important role in forest ecosystem functioning, but how climate change will affect the community composition and consequently bacterial functions is poorly understood. We assessed the effects of reduced precipitation with the aim of simulating realistic future...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    In: Neurology, 2015, Vol.84(17), pp.1782-1787
    Description: OBJECTIVES:: To investigate whether the human sciatic nerve might have a consistent somatotopic organization according to proximal fascicle input by spinal nerves. METHODS:: Twelve patients (55.3 ± 15.5 years) with confirmed lesions of either the L5 or S1 spinal nerve root underwent magnetic resonance neurography of sciatic nerve fascicles including thigh and knee levels (T2-weighted sequence with fat saturation, repetition time/echo time 7,552/52 milliseconds, voxel size 0.27 × 0.27 × 3.0 mm). Twenty healthy subjects and 12 additional patients with an established diagnosis of peripheral polyneuropathy served as 2 separate age- and sex-matched control groups. Two blinded readers assessed patients and controls for presence of distinct lesion patterns. Spatial maps of normalized T2 signal were rendered after segmentation and coregistration of sciatic nerve voxels to detect fascicle lesion patterns. RESULTS:: A clear somatotopic distribution of nerve fascicles was observed on cross-sections along the entire course of the sciatic nerve and was distinct between patients with L5 and those with S1 lesions. Fascicles emerging from L5 were ordered in anterolateral positions within sciatic nerve cross-sections, while fascicles emerging from S1 appeared posteromedially. Visual assessment discriminated these somatotopic lesions in all cases from both healthy and polyneuropathy controls. CONCLUSION:: A distinct pattern of somatotopy was identified within the sciatic nerve according to proximal fascicle input by L5 and S1 spinal nerves. Knowledge of human nerve somatotopy may have clinically useful implications in imaging-aided diagnosis of neuropathies.
    Keywords: Repetition ; Spinal Nerves ; Sciatic Nerve ; Segmentation ; Image Processing ; N.M.R. ; Maps ; Knee ; Polyneuropathy ; Neuropathy ; Neurology & Neuropathology;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 9
    Language: English
    In: Journal of Hydrology, 2006, Vol.319(1), pp.339-356
    Description: The delivery mechanisms of labile nutrients (e.g. NO , DON and DOC) to streams are poorly understood. Recent work has quantified the relationship between storm DOC dynamics and the connectedness of catchment units and between pre-storm wetness and transient groundwater NO flushing potential. While several studies have shown N and C flushing during storm events as the important mechanism in the export of DOC and DON in small catchments, the actual mechanisms at the hillslope scale have remained equivocal. The difficulty in isolating cause and effect in field studies is made difficult due to the spatial variability of soil properties, the limited ability to detect flow pathways within the soil, and other unknowns. Some hillslopes show preferential flow behavior that may allow transmission of hillslope runoff and labile nutrients with little matrix interaction; others do not. Thus, field studies are only partially useful in equating C and N sources with water flow and transport. This paper presents a new approach to the study of hydrological controls on labile nutrient flushing at the hillslope scale. We present virtual experiments that focus on quantifying the first-order controls on flow pathways and nutrient transport in hillslopes. We define virtual experiments as numerical experiments with a model driven by collective field intelligence. We present a new distributed model that describes the lateral saturated and vertical unsaturated water flow from hypothetical finite nutrient sources in the upper soil horizons. We describe how depth distributions of transmissivity and drainable porosity, soil depth variability, as well as mass exchange between the saturated and unsaturated zone influence the mobilization, flushing and release of labile nutrients at the hillslope scale. We argue that this virtual experiment approach may provide a well-founded basis for defining the first-order controls and linkages between hydrology and biogeochemistry at the hillslope scale and perhaps form a basis for predicting flushing and transport of labile nutrients from upland to riparian zones.
    Keywords: Virtual Experiments ; Hillslope Hydrology ; Nutrients ; Mobilization ; Flushing ; Runoff Generation ; Geography
    ISSN: 0022-1694
    E-ISSN: 1879-2707
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  • 10
    Language: English
    In: Journal Of Geophysical Research-Space Physics, 2011, Vol.116
    Description: The mobilization of mercury and dissolved organic carbon (DOC) during snowmelt often accounts for a major fraction of the annual loads. We studied the role of hydrological connectivity of riparian wetlands and upland/wetland transition zones to surface waters on the mobilization of Hg and DOC in Fishing...
    Keywords: Environmental Sciences Related To Agriculture And Land-Use ; Miljö- Och Naturvårdsvetenskap
    ISSN: 0148-0227
    E-ISSN: 21562202
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