Autoimmune diseases are believed to be highly dependent on loss of immune tolerance to selfantigens. Currently, no treatments have been successful clinically in inducing autoantigen-specific tolerance, including efforts to utilize antigen-specific immunotherapy (ASIT) to selectively correct the aberrant autoimmunity. Soluble antigen arrays (SAgAs) represent a novel autoantigen delivery system composed of a linear polymer, hyaluronic acid (HA), displaying multiple copies of conjugated autoantigen. We have previously reported that Soluble Antigen Arrays proteolipid protein (SAgA PLP) induced tolerance to a specific multiple sclerosis (MS) autoantigen, proteolipid peptide (PLP). Utilizing SAgA technology, we have developed a new ASIT as a possible type 1 diabetes (T1D) therapeutic by conjugating human insulin to HA, known as Soluble Antigen Array Insulin (SAgA Ins). Three types were synthesized: low valency lv SAgA Ins (2 insulins per HA), medium valency mv SAgA Ins (4 insulins per HA) and, high valency hv SAgA Ins (9 insulins per HA) to determine if valency differentially modulates the ex vivo activity of insulin-binding B cells
up by most immune cell populations but do not induce their maturation, and conventional dendritic cells are responsible for the brunt of antigen presentation within splenocytes. cSAgA p79 was more stimulatory than SAgA p79 both in vitro and in vivo, an effect that was ascribed to the peptide modification rather than the type of linkage. In summary, we provide here the first proof-ofprinciple that SAgA therapy could also be applicable to T1D.
Ferromagnetic fillers were incorporated within polydimethylsiloxane (PDMS) at concentrations of 0.1 wt% and 1 wt%. Deformation was detected via magnetic field response during compression tests. Testing of five of the six ferromagnetic fillers in PDMS revealed that 1 wt% was the minimum filler concentration required to detect compression via the magnetic field response. Settling of neodymium particles was evident; thus, Stokes' Law was used to investigate setting velocity of the particles. Overall, ferromagnetic fillers in PDMS cylinders provided a quantitative sensor of force and material displacement suggesting utility as sensors embedded in larger soft material constructs.
Materials and methods
Magnetic materialsCarbonyl iron microspheres, cobalt nanowires, and iron(II,III) oxide (iron oxide) nanopowder were all acquired from Sigma-Aldrich (St. Louis, MO, USA). The iron oxide contains a 97%
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