Cell-penetrating peptides (CPPs) hold great promise for intracellular delivery of therapeutic proteins. However, endosomal entrapment of transduced cargo is a major bottleneck hampering their successful application. While developing a transducible zinc finger protein-based artificial transcription factor targeting the expression of endothelin receptor A, we identified interaction between the CPP and the endosomal membrane or endosomal entanglement as a main culprit for endosomal entrapment.
View Article and Find Full Text PDFUsing scanning thermal microscopy, we have mapped the spatial distribution of temperatures in an operating nanoscale device formed from a magnetic injector, an Ag connecting wire, and a magnetic detector. An analytical model explained the thermal diffusion over the measured temperature range (2-300 K) and injector-detector separation (400-3000 nm). The characteristic diffusion lengths of the Peltier and Joule heat differ remarkably below 60 K, a fact that can be explained by the onset of ballistic phonon heat transfer in the substrate.
View Article and Find Full Text PDFDomain wall dynamics in wide submicrometer wires is investigated to understand the fundamental mechanisms that limit wall mobility, both experimentally by magneto-optical Kerr effect and by micromagnetic simulations. It is found that the dynamic domain wall structure departs significantly from the current description of a compact entity when evolving along the wire. The wall is composed of several substructures, each one propagating and evolving in a different dynamic regime with very different velocities.
View Article and Find Full Text PDFWe present magnetic quantum cellular automata (MQCA), fabricated by means of nanostencil lithography, i.e., using a resistless shadow masking technique in ultra-high vacuum.
View Article and Find Full Text PDFMost therapeutic monoclonal antibodies (mAbs) licensed for human use or in clinical development are indicated for treatment of patients with cancer and inflammatory/autoimmune disease and as such, are designed to directly interact with the immune system. A major hurdle for the development and early clinical investigation of many of these immunomodulatory mAbs is their inherent risk for adverse immune-mediated drug reactions in humans such as infusion reactions, cytokine storms, immunosuppression and autoimmunity. A thorough understanding of the immunopharmacology of a mAb in humans and animals is required to both anticipate the clinical risk of adverse immunotoxicological events and to select a safe starting dose for first-in-human (FIH) clinical studies.
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