mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan (R)-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20(+)/KRT5(-), 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20(+)/KRT- tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested)

A cell-based smoothed finite element method for kinematic limit analysis

This paper presents a new numerical procedure for kinematic limit analysis problems, which incorporates the cell-based smoothed finite element method with second-order cone programming. The application of a strain smoothing technique to the standard displacement finite element both rules out volumetric locking and also results in an efficient method that can provide accurate solutions with minimal computational effort. The non-smooth optimization problem is formulated as a problem of minimizing a sum of Euclidean norms, ensuring that the resulting optimization problem can be solved by an efficient second-order cone programming algorithm. Plane stress and plane strain problems governed by the von Mises criterion are considered, but extensions to problems with other yield criteria having a similar conic quadratic form or 3D problems can be envisaged

Zum Einspielverhalten von Flaechentragwerken

SIGLETIB: RN 4503(58) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Characterizing and reducing image distortions of hybrid PET-MRI systems

The combination of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) is a powerful hybrid imaging modality that visualizes functional and anatomical information. However, combining a PET and an MRI system is technically challenging. On the one hand, MRI uses strong and time-varying magnetic fields which can disturb or even destroy the electronic components of the PET system. On the other hand, the PET components can disturb the distribution of the magnetic fields of the MRI system and thereby cause Magnetic Resonance (MR) image artifacts. Especially, MRI switches low-frequency gradient magnetic fields. The time-varying magnetic fields induce eddy currents in all conductive components which produce superimposing magnetic fields. Since the gradient fields are used for spatial encoding, a distorted gradient field is also a source of imaging artifacts. The image artifacts can be severe especially for simultaneous PET-MRI systems because a PET system typically comprises many conductive components, such as heat spreaders, cooling pipes, radio-frequency shieldings or printed circuit boards with conductive planes. In this work, a Nuclear Magnetic Resonance (NMR) probe was developed to characterize the distortion of the gradient fields caused by different components of the PET system. Due to the capability of the NMR probe to measure magnetic fields in a time-resolved manner with high sensitivity at a single position, it was shown to be superior compared to the common characterization methods. Using the NMR probe, the RF shielding of a PET system was subsequently optimized with respect to the distortion of the magnetic fields of the MRI system. Furthermore, the distortion of the gradient fields caused by a complete PET system, i.e., a preclinical PET scanner, was quantitatively characterized. For this purpose, the gradient impulse response functions of the PET system were measured. Finally, the measured distortions of the gradient fields caused by the PET system were incorporated in the MRI reconstruction to correct for imaging artifacts. Summarizing, this thesis discusses methods for minimizing MRI artifacts caused by inserted electronic and conductive components both by selecting more suitable components and by retrospective correcting of remaining artifacts during reconstruction