Recombinant interferon-β1b (IFN-β1b) is an effective remedy against multiple sclerosis and other diseases. However, use of small polypeptide (molecular weight is around 18.5 kDa) is limited due to poor solubility, stability, and short half-life in systemic circulation. To solve this problem, we constructed two variants of PASylated IFN-β1b, with PAS sequence at C- or N-terminus of IFN-β1b. The PAS-modified proteins demonstrated 4-fold increase in hydrodynamic volume of the molecule combined with 2-fold increase of in vitro biological activity, as well as advanced stability and solubility of the protein in solution as opposed to unmodified IFN-β1b. Our results demonstrate that PASylation has a positive impact on stability, solubility, and functional activity of IFN-β1b and potentially might improve pharmacokinetic properties of the molecule as a therapeutic agent.
This paper addresses an active control of the resonant vibrations of
a sandwich plate with the honeycomb composition of a core ply performed by a
parametric stiffness modulation. The controlled vibrations are those of the
dominantly flexural type excited by a transverse force acting at a low
resonant frequency. The stiffness modulation is introduced by some fairly
small changes in an orientation of plates composing cell elements of a core
ply. It is performed at a comparatively high frequency identified by the
resonance of a mode of the dominantly shear type. The method of direct
partition of motions is used that predicts an existence of the modal
interaction between the low-frequency and the high-frequency motions. It is
shown that such a parametric control can provide a significant favourable
shift of the first eigenfrequency of a controlled beam (the one subjected to
the stiffness modulation) from its nominal value for an uncontrolled beam.
Asymptotic results are checked by direct time-marching integration. The energy
of the `micro-motions' is calculated and it is compared with the energies of
flexural vibrations of a plate with and without control. Heavy fluid loading
conditions are accounted for as well as material losses in a structure. It is
demonstrated that although heavy fluid loading reduces the resonant
frequencies of forced vibrations, the suggested mechanism of control
remains valid in these cases.
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