1,528 research outputs found

    Robust 4D-optimized treatment plans in scanned carbon ion beam therapy for intrafractionally moving lung cancer

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    Online monitoring of the Bragg peak during pig irradiation

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    A VOI-based 4D optimization method for the ion beam therapy of intrafractionally moving tumours

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    Confirmation of the tumour motion extraction method

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    Studying inter- and intrafraction motion mitigation with sequential 4DCTs of NSCLC patients

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    Plot and field scale soil moisture dynamics and subsurface wetness control on runoff generation in a headwater in the Ore Mountains

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    This study presents an application of an innovative sampling strategy to assess soil moisture dynamics in a headwater of the WeiĂźeritz in the German eastern Ore Mountains. A grassland site and a forested site were instrumented with two Spatial TDR clusters (STDR) that consist of 39 and 32 coated TDR probes of 60 cm length. Distributed time series of vertically averaged soil moisture data from both sites/ensembles were analyzed by statistical and geostatistical methods. Spatial variability and the spatial mean at the forested site were larger than at the grassland site. Furthermore, clustering of TDR probes in combination with long-term monitoring allowed identification of average spatial covariance structures at the small field scale for different wetness states. The correlation length of soil water content as well as the sill to nugget ratio at the grassland site increased with increasing average wetness and but, in contrast, were constant at the forested site. As soil properties at both the forested and grassland sites are extremely variable, this suggests that the correlation structure at the forested site is dominated by the pattern of throughfall and interception. We also found a very strong correlation between antecedent soil moisture at the forested site and runoff coefficients of rainfall-runoff events observed at gauge Rehefeld. Antecedent soil moisture at the forest site explains 92% of the variability in the runoff coefficients. By combining these results with a recession analysis we derived a first conceptual model of the dominant runoff mechanisms operating in this catchment. Finally, we employed a physically based hydrological model to shed light on the controls of soil- and plant morphological parameters on soil average soil moisture at the forested site and the grassland site, respectively. A homogeneous soil setup allowed, after fine tuning of plant morphological parameters, most of the time unbiased predictions of the observed average soil conditions observed at both field sites. We conclude that the proposed sampling strategy of clustering TDR probes is suitable to assess unbiased average soil moisture dynamics in critical functional units, in this case the forested site, which is a much better predictor for event scale runoff formation than pre-event discharge. Long term monitoring of such critical landscape elements could maybe yield valuable information for flood warning in headwaters. We thus think that STDR provides a good intersect of the advantages of permanent sampling and spatially highly resolved soil moisture sampling using mobile rods

    Parallelization of plan-optimization for TRiP98

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    Second messenger analogues highlight unexpected substrate sensitivity of CD38: total synthesis of the hybrid “L-cyclic inosine 5'-diphosphate ribose”

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    The multifunctional, transmembrane glycoprotein human CD38 catalyses the synthesis of three key Ca2+-mobilising messengers, including cyclic adenosine 5′-diphosphate ribose (cADPR), and CD38 knockout studies have revealed the relevance of the related signalling pathways to disease. To generate inhibitors of CD38 by total synthesis, analogues based on the cyclic inosine 5′-diphosphate ribose (cIDPR) template were synthesised. In the first example of a sugar hybrid cIDPR analogue, “L-cIDPR”, the natural “northern” N1-linked D-ribose of cADPR was replaced by L-ribose. L-cIDPR is surprisingly still hydrolysed by CD38, whereas 8-Br-L-cIDPR is not cleaved, even at high enzyme concentrations. Thus, the inhibitory activity of L-cIDPR analogues appears to depend upon substitution of the base at C-8; 8-Br-L-cIDPR and 8-NH2-L-cIDPR inhibit CD38-mediated cADPR hydrolysis (IC50 7 μM and 21 µM respectively) with 8-Br-L-cIDPR over 20-fold more potent than 8-Br-cIDPR. In contrast, L-cIDPR displays a comparative 75-fold reduction in activity, but is only ca 2-fold less potent than cIDPR itself. Molecular modelling was used to explore the interaction of the CD38 catalytic residue Glu-226 with the “northern” ribose. We propose that Glu226 still acts as the catalytic residue even for an L-sugar substrate. 8-Br-L-cIDPR potentially binds non-productively in an upside-down fashion. Results highlight the key role of the “northern” ribose in the interaction of cADPR with CD38

    Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore

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    Aims In the heart, a period of ischaemia followed by reperfusion evokes powerful cytosolic Ca2+ oscillations that can cause lethal cell injury. These signals represent attractive cardioprotective targets, but the underlying mechanisms of genesis are ill-defined. Here, we investigated the role of the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), which is known in several cell types to induce Ca2+ oscillations that initiate from acidic stores such as lysosomes, likely via two-pore channels (TPCs, TPC1 and 2). Methods and results An NAADP antagonist called Ned-K was developed by rational design based on a previously existing scaffold. Ned-K suppressed Ca2+ oscillations and dramatically protected cardiomyocytes from cell death in vitro after ischaemia and reoxygenation, preventing opening of the mitochondrial permeability transition pore. Ned-K profoundly decreased infarct size in mice in vivo. Transgenic mice lacking the endo-lysosomal TPC1 were also protected from injury. Conclusion NAADP signalling plays a major role in reperfusion-induced cell death and represents a potent pathway for protection against reperfusion injury
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