Do we betray errors beforehand? Using automated facial analysis to gather insights on learning from errors

Fischer C, Töniges T, Harteis C, Wrede B. Do we betray errors beforehand? Using automated facial analysis to gather insights on learning from errors. Presented at the 15th European Congress of Psychology, Amsterdam

Registration of serial sections: An evaluation method based on distortions of the ground truths

Registration of histological serial sections is a challenging task. Serial sections exhibit distortions and damage from sectioning. Missing information on how the tissue looked before cutting makes a realistic validation of 2D registrations extremely difficult. This work proposes methods for ground-truth-based evaluation of registrations. Firstly, we present a methodology to generate test data for registrations. We distort an innately registered image stack in the manner similar to the cutting distortion of serial sections. Test cases are generated from existing 3D data sets, thus the ground truth is known. Secondly, our test case generation premises evaluation of the registrations with known ground truths. Our methodology for such an evaluation technique distinguishes this work from other approaches. Both under- and over-registration become evident in our evaluations. We also survey existing validation efforts. We present a full-series evaluation across six different registration methods applied to our distorted 3D data sets of animal lungs. Our distorted and ground truth data sets are made publicly available.Comment: Supplemental data available under https://zenodo.org/record/428244

A large kindred of pulmonary fibrosis associated with a novel ABCA3 gene variant

Background: Interstitial lung disease occurring in children is a condition characterized by high frequency of cases due to genetic aberrations of pulmonary surfactant homeostasis, that are also believed to be responsible of a fraction of familial pulmonary fibrosis. To our knowledge, ABCA3 gene was not previously reported as causative agent of fibrosis affecting both children and adults in the same kindred. Methods: We investigated a large kindred in which two members, a girl whose interstitial lung disease was first recognized at age of 13, and an adult, showed a diffuse pulmonary fibrosis with marked differences in terms of morphology and imaging. An additional, asymptomatic family member was detected by genetic analysis. Surfactant abnormalities were investigated at biochemical, and genetic level, as well as by cell transfection experiments. Results: Bronchoalveolar lavage fluid analysis of the patients revealed absence of surfactant protein C, whereas the gene sequence was normal. By contrast, sequence of the ABCA3 gene showed a novel homozygous G > A transition at nucleotide 2891, localized within exon 21, resulting in a glycine to aspartic acid change at codon 964. Interestingly, the lung specimens from the girl displayed a morphologic usual interstitial pneumonitis-like pattern, whereas the specimens from one of the two adult patients showed rather a non specific interstitial pneumonitis-like pattern. Conclusions: We have detected a large kindred with a novel ABCA3 mutation likely causing interstitial lung fibrosis affecting either young and adult family members. We suggest that ABCA3 gene should be considered in genetic testing in the occurrence of familial pulmonary fibrosis

Bisulfite profiling of the MGMT promoter and comparison with routine testing in glioblastoma diagnostics

Background: Promoter methylation of the DNA repair gene O6 -methylguanine-DNA methyltransferase (MGMT) is an acknowledged predictive epigenetic marker in glioblastoma multiforme and anaplastic astrocytoma. Patients with methylated CpGs in the MGMT promoter beneft from treatment with alkylating agents, such as temozolomide, and show an improved overall survival and progression-free interval. A precise determination of MGMT promoter methyla‑ tion is of importance for diagnostic decisions. We experienced that diferent methods show partially divergent results in a daily routine. For an integrated neuropathological diagnosis of malignant gliomas, we therefore currently apply a combination of methylation-specifc PCR assays and pyrosequencing. Results: To better rationalize the variation across assays, we compared these standard techniques and assays to deep bisulfte sequencing results in a cohort of 80 malignant astrocytomas. Our deep analysis covers 49 CpG sites of the expanded MGMT promoter, including exon 1, parts of intron 1 and a region upstream of the transcription start site (TSS). We observed that deep sequencing data are in general in agreement with CpG-specifc pyrosequencing, while the most widely used MSP assays published by Esteller et al. (N Engl J Med 343(19):1350–1354, 2000. https://doi.org/ 10.1056/NEJM200011093431901) and Felsberg et al. (Clin Cancer Res 15(21):6683–6693, 2009. https://doi.org/10.1158/ 1078-0432.CCR-08-2801) resulted in partially discordant results in 22 tumors (27.5%). Local deep bisulfte sequencing (LDBS) revealed that CpGs located in exon 1 are suited best to discriminate methylated from unmethylated samples. Based on LDBS data, we propose an optimized MSP primer pair with 83% and 85% concordance to pyrosequencing and LDBS data. A hitherto neglected region upstream of the TSS, with an overall higher methylation compared to exon 1 and intron 1 of MGMT, is also able to discriminate the methylation status. Conclusion: Our integrated analysis allows to evaluate and redefne co-methylation domains within the MGMT pro‑ moter and to rationalize the practical impact on assays used in daily routine diagnostics

Myelination generates aberrant ultrastructure that is resolved by microglia

To enable rapid propagation of action potentials, axons are ensheathed by myelin, a multilayered insulating membrane formed by oligodendrocytes. Most of the myelin is generated early in development, resulting in the generation of long-lasting stable membrane structures. Here, we explored structural and dynamic changes in central nervous system myelin during development. To achieve this, we performed an ultrastructural analysis of mouse optic nerves by serial block face scanning electron microscopy (SBF-SEM) and confocal time-lapse imaging in the zebrafish spinal cord. We found that myelin undergoes extensive ultrastructural changes during early postnatal development. Myelin degeneration profiles were engulfed and phagocytosed by microglia using exposed phosphatidylserine as one “eat me” signal. In contrast, retractions of entire myelin sheaths occurred independently of microglia and involved uptake of myelin by the oligodendrocyte itself. Our findings show that the generation of myelin early in development is an inaccurate process associated with aberrant ultrastructural features that require substantial refinement.</p

Deutschland auf dem Weg zur Klimaneutralität 2045 - Szenarien und Pfade im Modellvergleich (Zusammenfassung)

Erstmals stellt die vorliegende Szenarienanalyse für Deutschland konkreteTransformationspfade zur Klimaneutralität 2045 auf der Basis eines umfassenden Modellvergleichs vor. Das Besondere an dieser Studie des Ariadne-Projektes ist, dass sechs Gesamtsystem- und Sek-tormodelle in einer Studie integriert wurden, die sich in ihren jeweiligen Stärken ergänzen: Für spezifische Fragestellungen wurde jeweils dasjenige Modell als Leitmodell hervorgehoben, welches die entsprechenden Aspekte am genauesten abbildet. Weitere Modelle wurden genutzt, um Auswirkungen der Transformation auf Umweltschutzgüter und die Verteilung der Kosten auf verschiedene Einkommensgruppen zu analysieren.Dieser breit gefächerte Ansatz ermöglicht es, die Implikationen der Energiewende robust und im Detail zu beschreiben

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease

Axonal degeneration determines the clinical outcome of multiple sclerosis and is thought to result from exposure of denuded axons to immune-mediated damage. Therefore, myelin is widely considered to be a protective structure for axons in multiple sclerosis. Myelinated axons also depend on oligodendrocytes, which provide metabolic and structural support to the axonal compartment. Given that axonal pathology in multiple sclerosis is already visible at early disease stages, before overt demyelination, we reasoned that autoimmune inflammation may disrupt oligodendroglial support mechanisms and hence primarily affect axons insulated by myelin. Here, we studied axonal pathology as a function of myelination in human multiple sclerosis and mouse models of autoimmune encephalomyelitis with genetically altered myelination. We demonstrate that myelin ensheathment itself becomes detrimental for axonal survival and increases the risk of axons degenerating in an autoimmune environment. This challenges the view of myelin as a solely protective structure and suggests that axonal dependence on oligodendroglial support can become fatal when myelin is under inflammatory attack