Asymptotic analysis of mode-coupling theory of active nonlinear microrheology

We discuss a schematic model of mode-coupling theory for force-driven active nonlinear microrheology, where a single probe particle is pulled by a constant external force through a dense host medium. The model exhibits both a glass transition for the host, and a force-induced delocalization transition, where an initially localized probe inside the glassy host attains a nonvanishing steady-state velocity by locally melting the glass. Asymptotic expressions for the transient density correlation functions of the schematic model are derived, valid close to the transition points. There appear several nontrivial time scales relevant for the decay laws of the correlators. For the nonlinear friction coeffcient of the probe, the asymptotic expressions cause various regimes of power-law variation with the external force, and two-parameter scaling laws.Comment: 17 pages, 12 figure

Expanding the Repertoire of Modified Vaccinia Ankara-Based Vaccine Vectors via Genetic Complementation Strategies

nkara (MVA) is a safe, highly attenuated orthopoxvirus that is being developed as a recombinant vaccine vector for immunization against a number of infectious diseases and cancers. However, the expression by MVA vectors of large numbers of poxvirus antigens, which display immunodominance over vectored antigens-of-interest for the priming of T cell responses, and the induction of vector-neutralizing antibodies, which curtail the efficacy of subsequent booster immunizations, remain as significant impediments to the overall utility of such vaccines. Thus, genetic approaches that enable the derivation of MVA vectors that are antigenically less complex may allow for rational improvement of MVA-based vaccines. during infection, and that the processes governing the generation of antiviral antibody responses are more readily saturated by viral antigen than are those that elicit CD8+ T cell responses. deletion, enables the generation of novel replication-defective MVA mutants and expands the repertoire of genetic viral variants that can now be explored as improved vaccine vectors

Force-induced diffusion in microrheology

We investigate the force-induced diffusive motion of a tracer particle inside a glass-forming suspension when a strong external force is applied to the probe (active nonlinear microrheology). A schematic model of mode-coupling theory introduced recently is extended to describe the transient dynamics of the probe particle, and used to analyze recent molecular-dynamics simulation data. The model describes non-trivial transient displacements of the probe before a steady-state velocity is reached. The external force also induces diffusive motion in the direction perpendicular to its axis. We address the relation between the transverse diffusion coefficient D⊥ and the force-dependent nonlinear friction coefficient ζ. Non-diffusive fluctuations in the direction of the force are seen at long times in the MD simulation, while the model describes cross-over to long-time diffusion

Modified recombinant human IgG1-Fc is superior to natural IVIG at inhibiting immune-mediated demyelination.

Intravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Although Fc fragments derived from IVIG have shown efficacy in controlling immune thrombocytopenia (ITP) in children, the mechanisms of action are unclear and controversial. The aim of this study is to dissect IVIG effector mechanisms using further adapted Fc fragments on demyelination in an ex vivo model of the central nervous system (CNS)-immune interface. Using organotypic cerebellar slice cultures (OSC) from transgenic mice we induced extensive immune-mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement. Protective effects of adapted Fc fragments were assessed by live imaging of GFP expression, immunohistochemistry and confocal microscopy. Cysteine and glycan adapted Fc fragments protected OSC from demyelination in a dose-dependent manner where equimolar concentrations of either IVIG or control Fc were ineffective. The protective effects of the adapted Fc fragments are partly attributed to interference with complement-mediated oligodendroglia damage. Transcriptome analysis ruled out signatures associated with inflammatory or innate immune responses. Taken together our findings show that recombinant biomimetics can be made that are at least two hundred-fold more effective than IVIG in controlling demyelination by anti-MOG antibodies