The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier

G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the “triple membrane bypass” pathway and the generation of reactive oxygen species. The recent recognition of GPCR transactivation of serine/threonine kinase receptors enormously broadens the GPCR signalling paradigm. It may be predicted that the transactivation of serine/threonine kinase receptors would have mechanistic similarities with transactivation of tyrosine kinase pathways; however, initial studies suggest that these two transactivation pathways are mechanistically distinct. Important questions are the relative importance of tyrosine and serine/threonine transactivation pathways, the contribution of transactivation to overall GPCR signalling, mechanisms of transactivation and the range of cell types in which this phenomenon occurs. The ultimate significance of transactivation-dependent signalling remains to be defined but it appears to be prominent and if so will represent a new cell signalling frontier.     

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.     

Compartmental analysis of efflux of extracellular space markers in rabbit detrusor muscle

Zusammenfassung Mit Hilfe des Computers wurde die Abgabe von [¹⁴C]-markiertem Mannit, Succrose und Inulin aus isoliertem Kaninchen-Detrusormuskel analysiert. Alle drei Verbindungen werden aus mindestens drei Abschnitten abgegeben und aus einer gebundenen Fraktion gelöst. Die Grösse des am raschesten von Mannit und Succrose beanspruchten Abschnittes entsprich derjenigen des Inulins.

---

---

Supported by a grant from the Medical Research Council of Canada.     

Anti-infective properties of bacteriocins: an update

Bacteriocin production is a widespread phenomenon among bacteria. Bacteriocins hold great promise for the treatment of diseases caused by pathogenic bacteria and could be used in the future as alternatives to existing antibiotics. The anti-infective potential of bacteriocins for inhibiting pathogens has been shown in various food matrices including cheese, meat, and vegetables. However, their inhibition of pathogens in vivo remains unclear and needs more investigation, due mainly to difficulties associated with demonstrating their health benefits. Many bacteriocins produced by established or potential probiotic organisms have been evaluated as potential therapeutic agents and interesting findings have been documented in vitro as well as in a few in vivo studies. Some recent in vivo studies point to the efficacy of bacteriocin-based treatments of human and animal infections. While further investigation remains necessary before the possibilities for bacteriocins in clinical practice can be described more fully, this review provides an overview of their potential applications to human and veterinary health.     

Forecasting of electricity price through a functional prediction of sale and purchase curves

This work proposes a new approach for the prediction of the electricity price based on forecasting aggregated purchase and sale curves. The basic idea is to model the hourly purchase and the sale curves, to predict them and to find the intersection of the predicted curves in order to obtain the predicted equilibrium market price and volume. Modeling and forecasting of purchase and sale curves is performed by means of functional data analysis methods. More specifically, parametric (FAR) and nonparametric (NPFAR) functional autoregressive models are considered and compared to some benchmarks. An appealing feature of the functional approach is that, unlike other methods, it provides insights into the sale and purchase mechanism connected with the price and demand formation process and can therefore be used for the optimization of bidding strategies. An application to the Italian electricity market (IPEX) is also provided, showing that NPFAR models lead to a statistically significant improvement in the forecasting accuracy.     

Forecasting the Dubai financial market with a combination of momentum effect with a deep belief network

Applying recent advances in machine learning techniques, we propose a hybrid model to forecast the Dubai financial market general index. Particularly, we exploit a deep belief networks model that applies a restricted Boltzmann machine as its main component in combination with momentum effects. We also introduce an innovative way of selecting the inputs by using momentum effects. With this hybrid methodology we generate a prediction model along with a comparison of three different linear models. The results obtained from the hybrid model are better and more stable than the three linear models. The findings support that the hybrid model we applied will find their way into finance because of their reliability and good performance.     

Diagnosing Business Incubation for Social Purpose: A Viable System Model Approach

Systemic Practice and Action Research - Business incubation is one of the means that promotes the overall business and economic growth of a particular location. However, to date, the role of...