Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance

Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies.Juvenile Diabetes Research Foundation Internationa

De l’atelier au laboratoire. Recherche et innovation dans l’industrie électrique XIX-XX siècles From workshop to laboratory. Research and innovation in electric industry, 19-20th centuries

The goal of the book is to explore the variety of ways in which innovative activities were carried out in the electrical industy from its pioneering phase in the mid-19th cebtury to the present. It is a shared assumption among historians of technology and economic historians alike that during the first half of the 20th century the mainsprings of innovation shifted from an activity pursued by a few highly creative individuals to one carried out by teams of specialists operating within industry, in structures specifically devoted to research. In electrical technology, as in other fields, the transition was gradual and it has continued to the present day. Laboratories, established in electrical engineering firms, were dominant but many of the advances in electrical technology originated from a variety of sites and environments that were not necessarily denominated as laboratories