473 research outputs found
Time-resolved measurement of the local equivalence ratio in a gaseous propane injection process using laser-induced gratings
This paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/abstract.cfm?URI=oe-14-26-12994. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.Peer reviewedPublisher PD
Marginality of bulk-edge correspondence for single-valley Hamiltonians
We study the correspondence between the non-trivial topological properties
associated with the individual valleys of gapped bilayer graphene (BLG), as a
prototypical multi-valley system, and the gapless modes at its edges and other
interfaces. We find that the exact connection between the valley-specific Hall
conductivity and the number of gapless edge modes does not hold in general, but
is dependent on the boundary conditions, even in the absence of intervalley
coupling. This non-universality is attributed to the absence of a well-defined
topological invariant within a given valley of BLG; yet, a more general
topological invariant may be defined in certain cases, which explains the
distinction between the BLG-vacuum and BLG-BLG interfaces.Comment: 7 pages, 4 figure
Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin
Cysteine cathepsins often contribute to cancer progression due to their overexpression in the tumour microenvironment and therefore present attractive targets for non-invasive diagnostic imaging. However, the development of highly selective and versatile small molecule probes for cathepsins has been challenging. Here, we targeted tumour-associated cathepsin B using designed ankyrin repeat proteins (DARPins). The selective DARPin 8h6 inhibited cathepsin B with picomolar affinity (Ki = 35 pM) by binding to a site with low structural conservation in cathepsins, as revealed by the X-ray structure of the complex. DARPin 8h6 blocked cathepsin B activity in tumours ex vivo and was successfully applied in in vivo optical imaging in two mouse breast cancer models, in which cathepsin B was bound to the cell membrane or secreted to the extracellular milieu by tumour and stromal cells. Our approach validates cathepsin B as a promising diagnostic and theranostic target in cancer and other inflammation-associated diseases
Immune system and peripheral nerves in propagation of prions to CNS
Prions are not only unique in the way they replicate. Also the sequence of events triggered by peripheral prion infection, generically termed ‘peripheral pathogenesis', sets prions aside from all other known pathogens. Whereas most bacteria, parasites, and viruses trigger innate and adaptive immune responses, the mammalian immune system appears to be remarkably oblivious to prions. Transmissible spongiform encephalopathies (TSEs) do not go along with inflammatory infiltrates, and antibodies to the prion protein are not typically raised during the course of the disease. On the other hand, there is conspicuous involvement of lymphoid organs, which accumulate sizeable concentrations of the infectious agent early during disease. Moreover, various states of immune deficiency can abolish peripheral pathogenesis and prevent ‘take' of infection when prions are administered to peripheral sites. Here, we critically re-visit the current evidence for an involvement of the immune system in prion diseases, and will attempt to trace the elaborate mechanisms by which prions, upon entry into the body from peripheral sites, reach the brai
Exploring conformational equilibria of a heterodimeric ABC transporter
ABC exporters pump substrates across the membrane by coupling ATP-driven movements of nucleotide binding domains (NBDs) to the transmembrane domains (TMDs), which switch between inward- and outward-facing (IF, OF) orientations. DEER measurements on the heterodimeric ABC exporter TM287/288 from Thermotoga maritima, which contains a non-canonical ATP binding site, revealed that in the presence of nucleotides the transporter exists in an IF/OF equilibrium. While ATP binding was sufficient to partially populate the OF state, nucleotide trapping in the pre- or post-hydrolytic state was required for a pronounced conformational shift. At physiologically high temperatures and in the absence of nucleotides, the NBDs disengage asymmetrically while the conformation of the TMDs remains unchanged. Nucleotide binding at the degenerate ATP site prevents complete NBD separation, a molecular feature differentiating heterodimeric from homodimeric ABC exporters. Our data suggest hydrolysis-independent closure of the NBD dimer, which is further stabilized as the consensus site nucleotide is committed to hydrolysis
Mega and Consumer Trends – Towards Car-independent Mobile Applications
The car industry is confronted with fundamental changes in society, technology and economy and forced to rethink its concept of mobility. Through constant strategic foresight, trend management and a holistic mobility vision, car manufacturers must develop innovative strategies that reflect current and future trends, in order to meet customer needs, technological standards and economic imperatives. Therefore, car manufacturers are shifting their value chain more and more towards the aftermarket and information technology (IT). Used as a tool for image branding and innovation monitoring, a closer look reveals that car manufacturers are constantly increasing their investment activities in technology start-ups. This indicates that the car industry is in the middle of a transformation process, transforming from a car producer to a mobility provider. Based on an analysis of future driving factors in the car industry and in-depth interviews, we identified six crucial megatrends: peak oil and global warming, connectedness, safety regulations, sharing economy, urban mobility and aging society. Furthermore, four shaping consumer trends were revealed: ownerless, simplicity, eco-lifestyle and personalization. In summary, the most successful providers in the mobile market might be those who understand thoroughly the consumers’ needs and behaviour, in order to offer the mobility services they desire
Activation of soluble guanylate cyclase reverses pulmonary vascular remodeling induced by hypoxia in mice
Pastorale Laienmitarbeiter in Seelsorgeeinheiten der Katholischen Kirche des Erzbistums Freiburg
Auf den Rückgang der Priesterzahlen reagiert das Erzbistum Freiburg mit der Bildung von Seelsorgeeinheiten, die sowohl aus Pfarreien als auch weiteren Gemeinschaftsformen bestehen.
Pastoral- und Gemeindereferenten nehmen dort vorwiegend Aufgaben im Bereich der Maryria wahr (Ausnahme: weibliche Pastoralreferenten). Die Bedeutung der Martyria ist auch unter Bezug auf den zeitlichen Aufwand am höchsten (Ausnahme: männliche Gemeindereferenten). Es liegt auf Basis einer fünf-fach Skalierung für alle Aufgaben eine hohe Motivation, durchschnittlich im Bereich zwischen 3,67 bis 3,91 vor. Die Motivstruktur ist ex- und intrinsisch geprägt, mit meist deutlichem Schwerpunkt auf den intrinsischen Motiven. Die Anreizsituation in den Seelsorgeeinheiten stellt sich beispielsweise mit der „communio-Ekklesiologie“ intrinsisch, mit den hierarchischen Elementen extrinsisch dar. Mit den extrinsischen Elementen besteht die Gefahr der Verdrängung von Motivation. Anreizsysteme sollten durch intrinsische Anreize (z.B. Kommunikation, Partizipation, Kooperation), die auch von der „communio-Ekklesiologie“ vertreten werden, bestimmt sein, ohne die extrinsische Seite z.B. durch Zahlung von Gehältern zu vernachlässigen
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