Analytical and computational study of magnetization switching in kinetic Ising systems with demagnetizing fields

An important aspect of real ferromagnetic particles is the demagnetizing field resulting from magnetostatic dipole-dipole interaction, which causes large particles to break up into domains. Sufficiently small particles, however, remain single-domain in equilibrium. This makes such small particles of particular interest as materials for high-density magnetic recording media. In this paper we use analytic arguments and Monte Carlo simulations to study the effect of the demagnetizing field on the dynamics of magnetization switching in two-dimensional, single-domain, kinetic Ising systems. For systems in the ``Stochastic Region,'' where magnetization switching is on average effected by the nucleation and growth of fewer than two well-defined critical droplets, the simulation results can be explained by the dynamics of a simple model in which the free energy is a function only of magnetization. In the ``Multi-Droplet Region,'' a generalization of Avrami's Law involving a magnetization-dependent effective magnetic field gives good agreement with our simulations.Comment: 29 pages, REVTeX 3.0, 10 figures, 2 more figures by request. Submitted Phys. Rev.

Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial

Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM Pegunigalsidase alfa, a novel PEGylated, covalently crosslinked form of α-galactosidase A developed as enzyme replacement therapy (ERT) for Fabry disease (FD), was designed to increase plasma half-life and reduce immunogenicity, thereby enhancing efficacy compared with available products. Symptomatic adults with FD participated in this open-label, 3-month dose-ranging study, followed by a 9-month extension. Three cohorts were enrolled in a stepwise manner, each receiving increased doses of pegunigalsidase alfa: 0.2, 1.0, 2.0 mg/kg, via intravenous infusion every other week. Pharmacokinetic analysis occurred on Day 1 and Months 3, 6, and 12. Kidney biopsies at baseline and Month 6 assessed peritubular capillary globotriaosylceramide (Gb3) content. Renal function, cardiac parameters, and other clinical endpoints were assessed throughout. Treatment-emergent adverse events (AEs) and presence of immunoglobulin G (IgG) antidrug antibodies (ADAs) were assessed. Sixteen patients completed 1 year's treatment. Mean terminal plasma half-life (each cohort) ranged from 53 to 121 hours. All 11 male and 1 of 7 female patients presented with classic FD phenotype, in whom renal peritubular capillary Gb3 inclusions were reduced by 84%. Mean estimated glomerular filtration rate was 111 mL/min/1.73 m 2 at baseline, remaining stable throughout treatment. Three patients developed treatment-induced IgG ADAs; following 1 year's treatment, all became ADA-negative. Nearly all treatment-emergent AEs were mild or moderate. One patient withdrew from the study following a serious related AE. Pegunigalsidase alfa may represent an advance in ERT for FD, based on its unique pharmacokinetics and apparent low immunogenicity