Functional Implications of Novel Human Acid Sphingomyelinase Splice Variants

BACKGROUND: Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity. METHODOLOGY/PRINCIPAL FINDINGS: We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models. CONCLUSIONS/SIGNIFICANCE: These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity

Virtual-Reality: Ein einführender Überblick

Virtual-Reality hat in den letzten Jahren zunehmend an Bedeutung gewonnen. Insbesondere die Verfügbarkeit günstiger (End-)Geräte (z. B. Samsung Gear, Google Cardboard) haben diesen Trend weiter verstärkt. Dabei bietet Virtual-Reality für Unternehmen vielfältige Anwendungsmöglichkeiten. So lassen sich etwa erklärungsbedürftige Produkte oder Dienstleistungen wesentlich besser präsentieren als mit klassischen Formen der Produktpräsentation. Virtual-Reality und die hiermit verbundenen Eigenschaften, wie etwa die Immersion (das Gefühl des Nutzers, sich an einem anderen Ort zu befinden), bietet nicht nur für Unternehmen aus der Gaming- oder Entertainmentbranche zahlreiche Möglichkeiten, sondern wird in Zukunft auch im (Online-)Handel immer wichtiger. Allerdings zeigt sich auch, das die Konzeption von Virtual-Reality-Produktionen durchaus komplex ist. Neben den technischen Herausforderungen bei der Aufnahme von geeignetem Bildmaterial und dessen digitaler Weiterverarbeitung müssen auch die Herausforderungen des VR-spezifischen Storytelling berücksichtigt werden. Die Autoren der vorliegenden Veröffentlichung geben einen Überblick über einige zentrale Aspekte dieser neuen Technologie. Die Veröffentlichung richtet sich an Unternehmer, die planen Virtual-Reality einzusetzen und sich einen ersten Überblick über zentrale Aspekte machen möchten

Drei aerobe Testverfahren im Vergleich : Conconi-Test, Laktatstufen-Test und die Bestimmung des maximalen Laktat-Steady-States (ILSmax-Test)

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Wavelength frame multiplication for reflectometry at long-pulse neutron sources

The European Spallation Source (ESS), which is under construction in Lund (Sweden), will be the next leading neutron facility with an unprecedented brilliance and novel long-pulse time structure. A long-pulse source not only provides a high time-average flux but also opens the possibility to tune the resolution by using pulse shaping choppers. Thus, an instrument can readily be operated in either a high flux or a high resolution mode. Several of the shorter instruments at the ESS will employ Wavelength Frame Multiplication (WFM) in order to enable a sufficient resolution while offering a continuous and broad wavelength range. A test beamline was operated until the end of 2019 at the research reactor in Berlin to test components and methods, including WFM, in order to prepare the new facility for the operation of neutron instruments and successful first science. We herein demonstrate the implementation of WFM for reflectometry. By selecting a short pulse mode under the same geometrical configuration, we compare and discuss the results for two reference samples. The reported experiments not only serve to prove the reliability of the WFM approach but also, for the first time, demonstrate the full instrument control, data acquisition and data reduction chain that will be implemented at the ESS

Obsolescence - affordable adaptive reuse

This thesis departures from the urgency to reinterpret the role of the architect. Our job’s main mission can no longer be to supply ideas for cradle to grave type of production. The only way to harmonize our needs with the planetary limits is through a paradigm shift towards reshaping existing materials, infrastructure, and constructions. How could architects better inform and convey their expertise regarding construction, material qualities, and cultural values, in a constructive, forward-looking way? By working hands-on with preexisting contexts and buildings we want to learn the craft of adaptive reuse. This thesis has resulted in a case study of a former hardware store, called Järnbolaget, in the small urban outpost Torsby in the north of Värmland