38 research outputs found
Deregulation of Letter Markets and its Impact on Process and Product Innovation
Does the European model of end-to-end competition or the US model of worksharing provide stronger innovation incentives for incumbent postal operators? We answer this question based on a two stage model with price competition and product differentiation. We find that incentives for process innovation in the upstream activities are stronger under end-to-end competition. Incentives for process innovation in delivery are stronger under worksharing, assuming that the entrant's demand under worksharing is higher than the decline in the incumbent's demand. Regarding product innovation, incentives depend on the access pric
Specific targeting of human caspases using designed ankyrin repeat proteins
Caspases play important roles in cell death, differentiation, and proliferation. Due to their high homology, especially of the active site, specific targeting of a particular caspase using substrate analogues is very difficult. Although commercially available small molecules based on peptides are lacking high specificity due to overlapping cleavage motives between different caspases, they are often used as specific tools. We have selected designed ankyrin repeat proteins (DARPins) against human caspases 1-9 and identified high-affinity binders for the targeted caspases, except for caspase 4. Besides previously reported caspase-specific DARPins, we generated novel DARPins (D1.73, D5.15, D6.11, D8.1, D8.4, and D9.2) and confirmed specificity for caspases 1, 5, 6, and 8 using a subset of caspase family members. In addition, we solved the crystal structure of caspase 8 in complex with DARPin D8.4. This binder interacts with non-conserved residues on the large subunit, thereby explaining its specificity. Structural analysis of this and other previously published crystal structures of caspase/DARPin complexes depicts two general binding areas either involving active site forming loops or a surface area laterally at the large subunit of the enzyme. Both surface areas involve non-conserved surface residues of caspase
NMR structure of the apoptosis- and inflammation-related NALP1 pyrin domain
Signaling in apoptosis and inflammation is often mediated by proteins of the death domain superfamily in the Fas/FADD/Caspase-8 or the Apaf-1/Caspase-9 pathways. This superfamily currently comprises the death domain (DD), death effector domain (DED), caspase recruitment domain (CARD), and pyrin domain (PYD) subfamilies. The PYD subfamily is most abundant, but three-dimensional structures are only available for the subfamilies DD, DED, and CARD, which have an antiparallel arrangement of six alpha helices as common fold. This paper presents the NMR structure of PYD of NALP1, a protein that is involved in the innate immune response and is a component of the inflammasome. The structure of NALP1 PYD differs from all other known death domain superfamily structures in that the third alpha helix is replaced by a flexibly disordered loop. This unique feature appears to relate to the molecular basis of familial Mediterranean fever (FMF), a genetic disease caused by single-point mutations
Erhebung der Kosten für die Grundversorgung - Vor- und Nachteile der Methoden
Der Schweizer Postmarkt soll für die Konkurrenz geöffnet werden. Gleichzeitig soll die Grundversorgung – der so genannte Service Public – weiterhin gewährleistet sein. Mit der Marktöffnung wird dem ehemaligen Monopolisten die Grundlage zur Finanzierung der Grundversorgung entzogen.
Zur Sicherstellung der Grundversorgung im Wettbewerb muss der ehemalige Monopolanbieter deshalb für die zusätzlichen Kosten entschädigt werden, die ihm aus der Grundversorgungsverpflichtung entstehen. Im Folgenden werden die drei wichtigsten Methoden zur Kostenermittlung der Grundversorgung – Net Avoided Cost, Entry Pricing und Profitability Cost – beschrieben. Es wird beurteilt, für welche Fragestellungen sich welche Methoden eignen und worin deren Vor- und Nachteile liegen
Deregulation of letter markets and its impact on process and product innovation
Does the European model of end-to-end competition or the US model of worksharing provide stronger innovation incentives for incumbent postal operators? We answer this question based on a two stage model with price competition and product differentiation. We find that incentives for process innovation in the upstream activities are stronger under end-to-end competition. Incentives for process innovation in delivery are stronger under worksharing, assuming that the entrant's demand under worksharing is higher than the decline in the incumbent's demand. Regarding product innovation, incentives depend on the access price
Sozialer Ausschluss in Integrationsklassen: Ansichtssache?
Diese Studie vergleicht verschiedene soziometrische Maße, welche die soziale Inklusion von Kindern mit sonderpädagogischem Förderbedarf (SFB) erfassen. Wir nehmen an, dass die soziale Teilhabe auch davon abhängt, wie sie gemessen wurde. Zudem testen wir, ob mit zunehmender Heterogenität der Klasse eine höhere Akzeptanz der Kinder einhergeht. Die Annahmen wurden mit sozialen Netzwerkdaten von 439 Lernenden in integrativen Klassenzimmern, die mit strukturierten Interviews gewonnen wurden, getestet. Die Resultate zeigen, dass die soziale Inklusion von Kindern mit SFB davon abhängt, welches soziometrische Maß verwendet wird. Zudem fällt die soziale Inklusion aller Lernenden mit zunehmender Heterogenität der Klasse höher aus. Wir diskutieren die Notwendigkeit einer ganzheitlichen Messung der sozialen Beziehungen eines Kindes sowie kontextueller Aspekte bei der Erfassung von sozialem Ausschluss. Wir schlussfolgern, dass nicht das Kind im Fokus stehen sollte, das nicht in die Klasse passt, sondern das Ausmaß, mit dem das schulische Umfeld auf die Bedürfnisse des jeweiligen Kindes eingehen kann
Deregulation of Letter Markets and its Impact on Process and Product Innovation
Does the European model of end-to-end competition or the US model of worksharing provide stronger innovation incentives for incumbent postal operators? We answer this question based on a two stage model with price competition and product differentiation. We find that incentives for process innovation in the upstream activities are stronger under end-to-end competition. Incentives for process innovation in delivery are stronger under worksharing, assuming that the entrant's demand under worksharing is higher than the decline in the incumbent's demand. Regarding product innovation, incentives depend on the access price.