Crosstalk model

NO donors have been used for more than a century in the treatment of cardiovascular diseases. Clearly, the NO/cGMP system plays a major role in platelet inhibition in vivo and in vitro, however, the complex regulation of cGM P levels, as well as the crosstalk to the cAMP system, makes it a signaling network that is not yet fully understood. The contribution of cGMP-independent mechanisms in NO signaling in platelets is far from clear. Careful use of the crucial genetically altered mouse models, the variety of NO donors with clear differences in biochemistry and functional platelet effects as well as the many so-called specific activatory or inhibitory research tools will certainly help to elucidate the still unknown areas of NO signaling in platelets in the near future. 

Another promising alternative to the rather restrictive MBLL model is the layer model using diffusion equation. Diffuse optical imaging provides a better model for photon migration where approximation of path length is possible. This would provide a much improved focal change information and potentially eliminate crosstalk noise. 

There are several future directions that NIR brain sensing and imaging research can take. In instrumentation, advances in time-resolve spectroscopic equipment may yield less expensive equipment and thus a more prolific use. This will allow for approximation of time of flight parameter providing a possible avenue for inferring path length. Theoretically, there is a need for better theoretical modeling to eliminate crosstalk noise. Possible improvements have already been introduced by Boas, et. al [8]. However, more human subject studies need to be conducted to... 

Fig. 3.5 Bidirectional crosstalk. The solid arrows indicate the known activation of molecular species while the dotted arrows indicate one possible model for bidirectional crosstalk. Current research only establishes a one-way crosstalk from GPCRs to NMDA receptor.

The results acquired so far have been described as a pathway, which rationalizes a subset of the experimental data but is necessarily incomplete. It is clear that the reality will be better modeled by a regulatory network involving feedback, crosstalk, and other pathways as described in the next section. 

Because of its rare occurrence and dose-independent manifestation, prediction of idiosyncratic hepatotoxicity is a huge challenge in drug discovery and development process (Chen et al., 2013b). It is expected that idiosyncratic hepatotoxicity involves multiple factors, multiple biological events, and complex mechanisms. Therefore, the final manifestation of idiosyncratic hepatotoxicity is believed to be a product of interaction of individual factors, that is, a crosstalk between chemical properties, host factors, and environmental factors, with a multiple determinant hypothesis (Li, 2002). This hypothesis may explain the poor performance of the current in silico models for prediction of idiosyncratic hepatotoxicity solely based on chemical structure. Cruz-Monteagudo... 

Jilkine, A., Maree, A.F., Edelstein-Keshet, L. (2007). Mathematical model for spatial segregation of the Rho-family GTPases based on inhibitory crosstalk. Bulletin of Mathematical Biology, Vol.69, pp. 1943-1978. 

Besides the skin, gut, and BBB, there are other coculture models exhibiting crosstalk between the cocultured cell types that were developed for measuring toxicity. For example, an epitheHal/fibroblast [Lang et al., 1998] coculture model of the bronchial epithelial was used to examine ozone toxicity. Bone resorption caused by PasteureUa multocida toxin was studied in an osteoclast/osteoblast direct contact coculture model [MuUan and Lax, 1998]. Brana et al. [1999] cultured 400-/um thick rat brain (hippocampal) slices on a membrane insert and cultured the murine macrophage cell line (RAW 264.7) underneath. When challenged with the HIV-1 derived Tat protein, neuronal cell death in the brain slice occurred only when cocultured with the macrophage cell line. This model could be used to identify neurotoxic soluble molecules released by macrophages. 

Binaural audio can be delivered to a listener over conventional stereo loudspeakers, but each loudspeaker (unlike headphones) creates significant crosstalk to the opposite ear. The cross-talk can be cancelled by preprocessing the speaker signals (called cross-talk cancellers) with the inverse of the 2 x 2 matrix of transfer functions from the speakers to the ears. Cross-talk cancellers use a model of the head to anticipate what cross-talk will occur, then add an out-of-phase cancellation signal to the opposite channel. Thus, the cross-talk is acoustically cancelled at the listener s ears. If the head responses of the listener are known, and if the listener s head remains fixed, an individualized cross-talk cancellation system can be designed that works extremely well. 

Liu, E, Rasmussen, C.J., and Pedersen, R.J.S. (1999) Experimental verification of a new model describing the influence of incomplete signal extinction ratio on the sensitivity degradation due to multiple interferometric crosstalk. IEEE Photonics Technol. Lett, 11 (1), 137-139. 

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