Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.

The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

Minimum size for a nanoscale temperature discriminator based on a thermochemical system.

What are the limits of size reduction for information processing devices based on chemical reactions? In this paper, we partially answer this question. We show that a thermochemical system can be used to design a discriminator of the parameters associated with oscillations of the ambient temperature. Depending on the amplitude and frequency of the oscillations, the system exhibits sharp transitions between different types of its time evolutions. This phenomenon can be used to discriminate between different parameter values describing the oscillating environment. We investigate the reliability of the thermochemical discriminator as a function of the number of molecules involved in the reactions. A stochastic model of chemical reactions and heat exchange with the neighborhood, in which the number of molecules explicitly appears, is introduced. For the selected values of the parameters, thermochemical discriminators operating with less than 10(5) molecules appear to be unreliable.

Chemical computing with reaction-diffusion processes.

Chemical reactions are responsible for information processing in living organisms. It is believed that the basic features of biological computing activity are reflected by a reaction-diffusion medium. We illustrate the ideas of chemical information processing considering the Belousov-Zhabotinsky (BZ) reaction and its photosensitive variant. The computational universality of information processing is demonstrated. For different methods of information coding constructions of the simplest signal processing devices are described. The function performed by a particular device is determined by the geometrical structure of oscillatory (or of excitable) and non-excitable regions of the medium. In a living organism, the brain is created as a self-grown structure of interacting nonlinear elements and reaches its functionality as the result of learning. We discuss whether such a strategy can be adopted for generation of chemical information processing devices. Recent studies have shown that lipid-covered droplets containing solution of reagents of BZ reaction can be transported by a flowing oil. Therefore, structures of droplets can be spontaneously formed at specific non-equilibrium conditions, for example forced by flows in a microfluidic reactor. We describe how to introduce information to a droplet structure, track the information flow inside it and optimize medium evolution to achieve the maximum reliability. Applications of droplet structures for classification tasks are discussed.

Information coding with frequency of oscillations in Belousov-Zhabotinsky encapsulated disks.

Information processing with an excitable chemical medium, like the Belousov-Zhabotinsky (BZ) reaction, is typically based on information coding in the presence or absence of excitation pulses. Here we present a new concept of Boolean coding that can be applied to an oscillatory medium. A medium represents the logical TRUE state if a selected region oscillates with a high frequency. If the frequency fails below a specified value, it represents the logical FALSE state. We consider a medium composed of disks encapsulating an oscillatory mixture of reagents, as related to our recent experiments with lipid-coated BZ droplets. We demonstrate that by using specific geometrical arrangements of disks containing the oscillatory medium one can perform logical operations on variables coded in oscillation frequency. Realizations of a chemical signal diode and of a single-bit memory with oscillatory disks are also discussed.

Multiargument logical operations performed with excitable chemical medium.

Assuming that a pulse of excitation corresponds to the logical "true" state one can use a chemical medium for information processing and construct devices that execute the basic binary logical operations. Here we discuss direct chemical realizations of four argument logical functions equivalent to special types of McCulloch-Pitts neuron. We demonstrate that if a proper geometrical arrangement of excitable and nonexcitable areas is used then the construction of the considered devices can be much simpler than in the case where they are composed of chemical binary logical gates.

Sensing the distance to a source of periodic oscillations in a nonlinear chemical medium with the output information coded in frequency of excitation pulses.

A spatially distributed excitable chemical medium can collect and process information coded in the propagating pulses of excitation. We consider the problem of distance sensing with the use of a nonlinear chemical medium. We demonstrate that a sensor that can feel the distance separating it from a source of periodic excitations can be constructed by a proper geometrical arrangement of excitable and nonexcitable regions. The sensor returns information about the distance in the frequency of outgoing pulses. The sensor functionality is tested by simulations based on the Rovinsky-Zhabotinsky model. The results are confirmed in experiments performed for a ruthenium-catalyzed Belousov-Zhabotinsky reaction.

On one dimensional chemical diode and frequency generator constructed with an excitable surface reaction.

The oxidation of carbon monoxide on a Pt(110) surface is considered as a medium for chemical information processing in which bits of information are represented by traveling pulses of high oxygen coverage. Using numerical simulations for a model of CO oxidation we demonstrate that in such system one dimensional chemical signal diode can be realized by setting a proper profile of temperature. We also show that a pulse splitting can occur on a temperature inhomogeneity. The phenomenon of pulse splitting can be used to construct one dimensional generator of a train of pulses with adjustable frequency.

T-shaped coincidence detector as a band filter of chemical signal frequency.

The construction of a reactor that works as a bandpass filter for a chemical signal is described and its potential applications are discussed. By a chemical signal we understand a train of concentration pulses propagating in a spatially distributed excitable medium.