Porcine Sialoadhesin (CD169/Siglec-1) Is an Endocytic Receptor that Allows Targeted Delivery of Toxins and Antigens to Macrophages

Sialoadhesin is exclusively expressed on specific subpopulations of macrophages. Since sialoadhesin-positive macrophages are involved in inflammatory autoimmune diseases, such as multiple sclerosis, and potentially in the generation of immune responses, targeted delivery of drugs, toxins or antigens via sialoadhesin-specific immunoconjugates may prove a useful therapeutic strategy. Originally, sialoadhesin was characterized as a lymphocyte adhesion molecule, though recently its involvement in internalization of sialic acid carrying pathogens was shown, suggesting that sialoadhesin is an endocytic receptor. In this report, we show that porcine sialoadhesin-specific antibodies and F(ab')2 fragments trigger sialoadhesin internalization, both in primary porcine macrophages and in cells expressing recombinant porcine sialoadhesin. Using chemical inhibitors, double immunofluorescence stainings and dominant-negative constructs, porcine sialoadhesin internalization was shown to be clathrin- and Eps15-dependent and to result in targeting to early endosomes but not lysosomes. Besides characterizing the sialoadhesin endocytosis mechanism, two sialoadhesin-specific immunoconjugates were evaluated. We observed that porcine sialoadhesin-specific immunotoxins efficiently kill sialoadhesin-expressing macrophages. Furthermore, porcine sialoadhesin-specific albumin immunoconjugates were shown to be internalized in macrophages and immunization with these immunoconjugates resulted in a rapid and robust induction of albumin-specific antibodies, this compared to immunization with albumin alone. Together, these data expand sialoadhesin functionality and show that it can function as an endocytic receptor, a feature that cannot only be misused by sialic acid carrying pathogens, but that may also be used for specific targeting of toxins or antigens to sialoadhesin-expressing macrophages

High efficient modular drive system — An ideal approach for green intralogistics applications

This paper introduces an efficient modular solution kit for intralogistic drives, which reduces the total energy consumption of all drives in an automated warehouse by more than 15%. The reduction of energy consumption results from the interaction of optimized components (motors, control techniques and regeneration units), which are described in detail in this paper. Different motor concepts like the induction motor, the synchronous reluctance motor and the permanent magnet synchronous machine are compared according to the special requirements for intralogistics applications. Different control techniques are presented in order to achieve sensorless and efficient-optimal operation of these motors. The sensorless control technique uses signal injection to detect the rotor position sufficiently exact also in case of speed near standstill. Efficient-optimal operation is achieved by reducing the motor current with regard to the torque (MTPA-control). Furthermore this paper introduces a regeneration unit that can be connected between the DC link of frequency inverters and the mains to feed back regenerative energy. The regeneration unit consisting of a buck converter, a synchronous inverter and a line-filter can work in parallel to commonly used uncontrolled rectifiers. Its functioning is shown with the help of measurement results of a 1kW laboratory prototype. The last section shows a demonstrator in which a conventional conveyer system (with induction motor and braking resistor) is compared with an optimized one using the presented components. Power versus time measurements show specific energy savings resulting from the interaction of the optimized components

Social Media Marketing

In diesem Beitrag wird ein Planungsprozess mit seinen einzelnen Phasen für ein Social Media Marketing vorgestellt. Darüber hinaus werden zentrale Implementierungsoptionen beschrieben. Hierzu gehören Werbung (über Plattformen und Influencer), Kundenservice, Community Management, Social Recruitment, interne Nutzung und Business Profile