53 research outputs found

    Coupled modelling of subsurface water flux for an integrated flood risk management

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    Flood events cause significant damage not only on the surface but also underground. Infiltration of surface water into soil, flooding through the urban sewer system and, in consequence, rising groundwater are the main causes of subsurface damage. The modelling of flooding events is an important part of flood risk assessment. The processes of subsurface discharge of infiltrated water necessitate coupled modelling tools of both, surface and subsurface water fluxes. Therefore, codes for surface flooding, for discharge in the sewerage system and for groundwater flow were coupled with each other. A coupling software was used to amalgamate the individual programs in terms of mapping between the different model geometries, time synchronization and data exchange. The coupling of the models was realized on <i>two</i> scales in the Saxon capital of Dresden (Germany). As a result of the coupled modelling it could be shown that surface flooding dominates processes of any flood event. Compared to flood simulations without coupled modelling no substantial changes of the surface inundation area could be determined. Regarding sewerage, the comparison between the influx of groundwater into sewerage and the loading due to infiltration by flood water showed infiltration of surface flood water to be the main reason for sewerage overloading. Concurrent rainfalls can intensify the problem. The infiltration of the sewerage system by rising groundwater contributes only marginally to the loading of the sewerage and the distribution of water by sewerage has only local impacts on groundwater rise. However, the localization of risk areas due to rising groundwater requires the consideration of all components of the subsurface water fluxes. The coupled modelling has shown that high groundwater levels are the result of a multi-causal process that occurs before and during the flood event

    Genotyping of circulating tumor DNA in cholangiocarcinoma reveals diagnostic and prognostic information

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    Diagnosis of Cholangiocarcinoma (CCA) is difficult, thus a noninvasive approach towards (i) assessing and (ii) monitoring the tumor-specific mutational profile is desirable to improve diagnosis and tailor treatment. Tumor tissue and corresponding ctDNA samples were collected from patients with CCA prior to and during chemotherapy and were subjected to deep sequencing of 15 genes frequently mutated in CCA. A set of ctDNA samples was also submitted for 710 gene oncopanel sequencing to identify progression signatures. The blood/tissue concordance was 74% overall and 92% for intrahepatic tumors only. Variant allele frequency (VAF) in ctDNA correlated with tumor load and in the group of intrahepatic CCA with PFS. 63% of therapy naive patients had their mutational profile changed during chemotherapy. A set of 76 potential progression driver genes was identified among 710 candidates. The molecular landscape of CCA is accessible via ctDNA. This could be helpful to facilitate diagnosis and personalize and adapt therapeutic strategies

    Structure of the dimeric N-glycosylated form of fungal β-N-acetylhexosaminidase revealed by computer modeling, vibrational spectroscopy, and biochemical studies

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    <p>Abstract</p> <p>Background</p> <p>Fungal β-<it>N</it>-acetylhexosaminidases catalyze the hydrolysis of chitobiose into its constituent monosaccharides. These enzymes are physiologically important during the life cycle of the fungus for the formation of septa, germ tubes and fruit-bodies. Crystal structures are known for two monomeric bacterial enzymes and the dimeric human lysosomal β-<it>N</it>-acetylhexosaminidase. The fungal β-<it>N</it>-acetylhexosaminidases are robust enzymes commonly used in chemoenzymatic syntheses of oligosaccharides. The enzyme from <it>Aspergillus oryzae </it>was purified and its sequence was determined.</p> <p>Results</p> <p>The complete primary structure of the fungal β-<it>N</it>-acetylhexosaminidase from <it>Aspergillus oryzae </it>CCF1066 was used to construct molecular models of the catalytic subunit of the enzyme, the enzyme dimer, and the <it>N</it>-glycosylated dimer. Experimental data were obtained from infrared and Raman spectroscopy, and biochemical studies of the native and deglycosylated enzyme, and are in good agreement with the models. Enzyme deglycosylated under native conditions displays identical kinetic parameters but is significantly less stable in acidic conditions, consistent with model predictions. The molecular model of the deglycosylated enzyme was solvated and a molecular dynamics simulation was run over 20 ns. The molecular model is able to bind the natural substrate – chitobiose with a stable value of binding energy during the molecular dynamics simulation.</p> <p>Conclusion</p> <p>Whereas the intracellular bacterial β-<it>N</it>-acetylhexosaminidases are monomeric, the extracellular secreted enzymes of fungi and humans occur as dimers. Dimerization of the fungal β-<it>N</it>-acetylhexosaminidase appears to be a reversible process that is strictly pH dependent. Oligosaccharide moieties may also participate in the dimerization process that might represent a unique feature of the exclusively extracellular enzymes. Deglycosylation had only limited effect on enzyme activity, but it significantly affected enzyme stability in acidic conditions. Dimerization and <it>N</it>-glycosylation are the enzyme's strategy for catalytic subunit stabilization. The disulfide bridge that connects Cys<sup>448 </sup>with Cys<sup>483 </sup>stabilizes a hinge region in a flexible loop close to the active site, which is an exclusive feature of the fungal enzymes, neither present in bacterial nor mammalian structures. This loop may play the role of a substrate binding site lid, anchored by a disulphide bridge that prevents the substrate binding site from being influenced by the flexible motion of the loop.</p

    Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

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    BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients

    Schnelle Laufzeitberechnungen mit Anwendungen auf die Prestack-Kirchhoff-Migration

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    Available from FIZ Karlsruhe / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

    True-amplitude angle migration in complex media

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    We are presenting results from a true-amplitude prestack depth migration in the angle/azimuth domain. The implementation is based on the generalized Radon transform. Working directly in the angle/azimuth domain means that we do not need to calculate any Beylkin-determinant, and multi-valued traveltimes, in the presence of caustics, are naturally unfolded allowing for true-amplitude results even beneath a complex overburden. Such an implementation has until recently been considered unfeasible due to the computational complexity for large 3D volume migration. Our implementation is made possible through a massively parallel implementation with fast access to large dataset

    FRTM - a productive framework for reverse time migration

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    We have identified challenges upcoming hardware development is going to impose on RTM implementations. The increasing heterogeneity and complexity of target machines needs to be transparently mapped into the software layer. An efficient fault tolerance mechanism needs to be provided and I/O latencies need to be efficiently hidden. We have introduced a framework for RTM which is able to solve these problems. The framework is data dependency driven on two granularity levels. On the coarse level, concurrent computation of shots is powered by GPI-Space, a parallel development and execution framework. GPI-Space boosts our RTM framework by introducing a fault tolerant execution layer, an efficient topology mapping and an on the fly resource management. On the fine level, the computation of one shot is handled by domain decomposition in a task based model. The tight coupling between neighbouring domains is efficiently relaxed by the one sided asynchronous communication API GPI -2.0. Weak synchronization primitives allow for a fine granular and application specific breakup of data synchronization points with optimal overlap of communication by computation. Our framework has an inherent separation of parallelization and computation. Domain experts concentrate on the implementation of domain knowledge. Computer scientist can simultaneously do the parallelization and optimization

    Surface models for coupled modelling of runoff and sewer flow in urban areas

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    Traditional methods fail for the purpose of simulating the complete flow process in urban areas as a consequence of heavy rainfall and as required by the European Standard EN-752 since the bi-directional coupling between sewer and surface is not properly handled. The new methodology, developed in the EUREKA-project RisUrSim, solves this problem by carrying out the runoff on the basis of shallow water equations solved on high-resolution surface grids. Exchange nodes between the sewer and the surface, like inlets and manholes, are located in the computational grid and water leaving the sewer in case of,surcharge is further distributed on the surface. Dense topographical information is needed to build a model suitable for hydrodynamic runoff calculations; in urban areas, in addition, many line-shaped elements like houses, curbs, etc. guide the runoff of water and require polygonal input. Airborne data collection methods offer a great chance to economically gather densely sampled input data

    Maths in flood protection

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    The 2002 flooding of the Elbe River in Dresden, Germany, showed that apart from the obvious destruction caused by surface water, considerable damage was caused by groundwater and water from the sewer system. Groundwater levels can rise quickly due to overflowing sewers or above-ground flow, causing basement flooding and structural damage to houses. Thus, a coupled simulation of the three components surface water, groundwater and the sewer system is important for flood risk management

    3-D seismic imaging in crystalline rock environments: an approach based on diffraction focusing

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    Diffracted waves are seismic waves that backscatter from localized discontinuities in the earth. They describe backscattering from interfaces with either a curvature locally approaching infinity or occur if medium properties change on a scale smaller than the predominant seimic wavelength. Both types of diffracted events are of great importance in seismic processing as they allow to identify the presence of small inhomogeneities, truncations, faults, or pinch-out layers. However, to reliable interpret such subsurface features, diffractions should be properly imaged. An inherent part of the imaging is therefore a velocity model building tuned to diffractions. We present a method for 3-D velocity analysis based on the medium's diffraction response. We propose to evaluate a focusing norm along diffraction traveltimes in the time domain. The focusing analysis considers both amplitude and phase of the diffracted events which results in several output volumes: three migration velocities for point diffractions, and one migration velocity and azimuth for edge diffractions. As additional information, the focusing analysis provides two coherence volumes which can be used to classify the back-scattering geology. Application of the proposed imaging strategy to 3-D seismic field data, acquired in the context of geothermal exploration in eastern Germany, reveals that crystalline rocks cause a rich diffraction response whose focusing can provide complementary insight into structures that are notoriously hard to image conventionally
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