On the Effect of Inter-observer Variability for a Reliable Estimation of Uncertainty of Medical Image Segmentation

Uncertainty estimation methods are expected to improve the understanding and quality of computer-assisted methods used in medical applications (e.g., neurosurgical interventions, radiotherapy planning), where automated medical image segmentation is crucial. In supervised machine learning, a common practice to generate ground truth label data is to merge observer annotations. However, as many medical image tasks show a high inter-observer variability resulting from factors such as image quality, different levels of user expertise and domain knowledge, little is known as to how inter-observer variability and commonly used fusion methods affect the estimation of uncertainty of automated image segmentation. In this paper we analyze the effect of common image label fusion techniques on uncertainty estimation, and propose to learn the uncertainty among observers. The results highlight the negative effect of fusion methods applied in deep learning, to obtain reliable estimates of segmentation uncertainty. Additionally, we show that the learned observers' uncertainty can be combined with current standard Monte Carlo dropout Bayesian neural networks to characterize uncertainty of model's parameters.Comment: Appears in Medical Image Computing and Computer Assisted Interventions (MICCAI), 201

Spin-polarization of platinum (111) induced by the proximity to cobalt nanostripes

We measured a spin polarization above a Pt (111) surface in the vicinity of a Co nanostripe by spin-polarized scanning tunneling spectroscopy. The spin polarization is exponentially decaying away from the Pt/Co interface and is detectable at distances larger than 1 nm. By performing self-consistent ab-initio calculations of the electronic-structure for a related model system we reveal the interplay between the induced magnetic moments within the Pt surface and the spin-resolved electronic density of states above the surface.Comment: 19 pages, 6 figure

A Coursebook in a Trilingual Classroom: To Use or not to Use

Coursebook use has proved to be a controversial issue in methodology. In this paper we refer to different writing on this subject, and take the argument a step further. As the way out, we look at an aspect of teaching English as a foreign language (EFL) that sooner or later every teacher comes up against – a need to write his/her materials. As our research has shown, this becomes of major importance in a trilingual classroom. Here, we also refer to some of the theoretical positions underlying third language acquisition (TLA)

Untersuchungen zur Funktion des Intermediarfilamentproteins Vimentin <i>in vivo</i>

Vimentin ist ein Intermediarfilament-Protein (IF) und wird in unterschiedlich differenzierten Zellen mesenchymalen Ursprungs exprimiert. Zudem ist Vimentin das Haupt-IF im Epithel und den kortikalen Faserzellen der Linse. Mit GFAP bildet Vimentin das Zytoskelett der Gliazellen der Retina und des ZNS. Neben seinem Beitrag zur mechanischen Integrität der Zelle wird für Vimentin eine Funktion im Lipidmetabolismus, in der Stressantwort, bei Apoptose und im Vesikeltransport postuliert. Überraschenderweise entwickeln Vimentin defiziente Mäuse ohne Stressinduktion, jedoch keinen offensichtlichen Phänotyp, was möglicherweise seine Ursache in kompensatorischen Effekten anderer IF-Proteine hat. Die spezielle Funktion von Vimentin in der Entwicklung und in Geweben ist dadurch in vivo noch weitgehend unverstanden. In dieser Arbeit konnte durch substöchiometrische, gewebespezifische Expression einer dominant negativen Vimentin Mutante gezeigt werden, dass Vimentin eine bedeutende Rolle für die Integrität der Linse hat und die Expression von GFAP auf transkriptioneller Ebene indirekt moduliert. In der Linse verursachte die Aggregation des Vimentin Proteins eine Zunahme der Faserzellgröße und führte zu Einfaltungen der Plasmamembranen. Als endgültige Pathologie entwickelten die mutiertes Vimentin exprimierenden Mäuse einen posterioren Katarakt. Dies ordnet Vimentin, und nicht den linsenspezifischen IF-Proteinen CP49 und Filensin, die Hauptrolle in der Erhaltung der Linsenintegrität zu. Im Laufe der Differenzierung der Linsenfaser werden die Vimentin Aggregate degradiert, was durch erhöhte Expression von dem Chaperonen Hsp70, Ubiquitinierung und erhöhter Proteasomenaktivität begleitet wird und den Aggregat-Abbauweg darstellt. In den Astrogliazellen der Retina und in Linsenepithelzellen löste die Expression von mutiertem Vimentin die vermehrte Expression von GFAP auf transkriptioneller und Proteinebene aus. Die erhöhte Expression von GFAP wird durch die Aktivierung des Transkriptionsfaktors Stat3 durch Relokalisation in den Kern der Gliazellen induziert. Dies deutet eine Aktivierung der Astroglia als Stressantwort auf mutiertes Vimentin in diesen Zellen an, die analog zu intrazellulären Prozessen in der reaktiven Gliose steht und beschreibt zum ersten Mal einen Mechanismus, in dem ein mutiertes Zytoskelettprotein zu Veränderung der Genexpression beiträgt. Zusammengefasst postulieren die in dieser Arbeit erstellten Ergebnisse eine Beteiligung von Vimentin an genetisch bedingten humanen Katarakt- und Retinaerkrankungen.Novel in vivo function of vimentin Vimentin is the major cytoskeletal protein of mesenchyme. Remarkably, vimentin-deficient mice develop only subtle defects. Here, we investigated vimentin function by expressing a point-mutated gene (VimR113C) in transgenic mice. Low amounts of VimR113C disrupted the vimentin network without consequences for embryogenesis and tissue homeostasis. In lens fiber cells, VimR113C formed aggregates and a posterior cataract, suggesting a major role during fiber cell extension. Central, postmitotic fibers became depleted of aggregates, demonstrating the transient nature of protein aggregates. This process was mediated by upregulation of Hsp70, ubiquitination and increased proteasome activity. In retinal glial cells and the lens epithelium, VimR113C caused a strong upregulation of GFAP-mRNA and protein, indicating that it is sufficient to induce reactive gliosis. Of note, GFAP upregulation was mediated by nuclear translocation of STAT3 in Müller glial cells. This provides a mechanistic link between mutations in a cytoskeletal protein and changes in gene expression. We hypothesize that vimentin mutations may cause cataracts and retinal degeneration in humans

Live Follow-Up of Enzymatic Reactions Inside the Cavities of Synthetic Giant Unilamellar Vesicles Equipped with Membrane Proteins Mimicking Cell Architecture

Compartmentalization of functional biological units, cells, and organelles serves as an inspiration for the development of biomimetic materials with unprecedented properties and applications in biosensing and medicine. Because of the complexity of cells, the design of ideal functional materials remains a challenge. An elegant strategy to obtain cell-like compartments as novel materials with biofunctionality is the combination of synthetic micrometer-sized giant unilamellar vesicles (GUVs) with biomolecules because it enables studying the behavior of biomolecules and processes within confined cavities. Here we introduce a functional cell-mimetic compartment formed by insertion of the model biopore bacterial membrane protein OmpF in thick synthetic membranes of an artificial GUV compartment that enclosesâEuro"as a modelâEuro"the oxidative enzyme horseradish peroxidase. In this manner, a simple and robust cell mimic is designed: the biopore serves as a gate that allows substrates to enter cavities of the GUVs, where they are converted into products by the encapsulated enzyme and then released in the environments of GUVs. Our bioequipped GUVs facilitate the control of specific catalytic reactions in confined microscale spaces mimicking cell size and architecture and thus provide a straightforward approach serving to obtain deeper insights into biological processes inside cells in real time