RESUMO
Chimeric drugs with selective potential toward specific cell types constitute one of the most promising forefronts of modern Pharmacology. We present a mathematical model to test and optimize these synthetic constructs, as an alternative to conventional empirical design. We take as a case study a chimeric construct composed of epidermal growth factor (EGF) linked to different mutants of interferon (IFN). Our model quantitatively reproduces all the experimental results, illustrating how chimeras using mutants of IFN with reduced affinity exhibit enhanced selectivity against cell overexpressing EGF receptor. We also investigate how chimeric selectivity can be improved based on the balance between affinity rates, receptor abundance, activity of ligand subunits, and linker length between subunits. The simplicity and generality of the model facilitate a straightforward application to other chimeric constructs, providing a quantitative systematic design and optimization of these selective drugs against certain cell-based diseases, such as Alzheimer's and cancer.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e26; doi:10.1038/psp.2013.2; advance online publication 13 February 2013.
RESUMO
We study the response of Turing stripe patterns to a simple spatiotemporal forcing. This forcing has the form of a traveling wave and is spatially resonant with the characteristic Turing wavelength. Experiments conducted with the photosensitive chlorine dioxide-iodine-malonic acid reaction reveal a striking symmetry-breaking phenomenon of the intrinsic striped patterns giving rise to hexagonal lattices for intermediate values of the forcing velocity. The phenomenon is understood in the framework of the corresponding amplitude equations, which unveils a complex scenario of dynamical behaviors.
RESUMO
We present a theoretical and experimental study of the sideband instabilities in Turing patterns of stripes. We compare numerical computations of the Brusselator model with experiments in a chlorine dioxide-iodine-malonic acid (CDIMA) reaction in a thin gel layer reactor in contact with a continuously refreshed reservoir of reagents. Spontaneously evolving Turing structures in both systems typically exhibit many defects that break the symmetry of the pattern. Therefore, the study of sideband instabilities requires a method of forcing perfect, spatially periodic Turing patterns with the desired wave number. This is easily achieved in numerical simulations. In experiments, the photosensitivity of the CDIMA reaction permits control and modulation of Turing structures by periodic spatial illumination with a wave number outside the stability region. When a too big wave number is imposed on the pattern, the Eckhaus instability may arise, while for too small wave numbers an instability sets in forming zigzags. By means of the amplitude equation formalism we show that, close to the hexagon-stripe transitions, these sideband instabilities may be preceded by an amplitude instability that grows transient spots locally before reconnecting with stripes. This prediction is tested in both the reaction-diffusion model and the experiment.
RESUMO
We study, both theoretically and experimentally, the dynamical response of Turing patterns to a spatiotemporal forcing in the form of a traveling-wave modulation of a control parameter. We show that from strictly spatial resonance, it is possible to induce new, generic dynamical behaviors, including temporally modulated traveling waves and localized traveling solitonlike solutions. The latter make contact with the soliton solutions of Coullet [Phys. Rev. Lett. 56, 724 (1986)]] and generalize them. The stability diagram for the different propagating modes in the Lengyel-Epstein model is determined numerically. Direct observations of the predicted solutions in experiments carried out with light modulations in the photosensitive chlorine dioxide-iodine-malonic acid reaction are also reported.
