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The central nervous system is themost complex network of the human body. The existence and functionality of a large number of molecular species in human brain are still ambiguous and mostly unknown, thus posing a challenge to Science and Medicine. Neurological diseases inherit the same level of complexity,making effective treatments difficult to be found. Multiple sclerosis (MS) is a major neurological disease that causes severe inabilities and also a significant social burden on health care system: between 2 and 2.5million people are affected by it, and the cost associated with it is significantly higher as compared with other neurological diseases because of the chronic nature of the disease and to the partial efficacy of current therapies. Despite difficulties in understanding and treating MS,many computationalmodels have been developed to help neurologists. In the present work, we briefly review the main characteristics of MS and present a selection criteria ofmodeling approaches. [ABSTRACT FROM AUTHOR]

Motivation: Vaccines represent the most effective and cost-efficient weapons against a wide range of diseases. Nowadays new generation vaccines based on subunit antigens reduce adverse effects in high risk individuals. However, vaccine antigens are often poor immunogens when administered alone. Adjuvants represent a good strategy to overcome such hurdles, indeed they are able to: enhance the immune response; allow antigens sparing; accelerate the specific immune response; and increase vaccine efficacy in vulnerable groups such as newborns, elderly or immune-compromised people. However, due to safety concerns and adverse reactions, there are only a few adjuvants approved for use in humans. Moreover, in practice current adjuvants sometimes fail to confer adequate stimulation. Hence, there is an imperative need to develop novel adjuvants that overcome the limitations of the currently available licensed adjuvants. Results: We developed a computational framework that provides a complete pipeline capable of predicting the best citrus-derived adjuvants for enhancing the immune system response using, as a target disease model, influenza A infection. In silico simulations suggested a good immune effi- cacy of specific citrus-derived adjuvant (Beta Sitosterol) that was then confirmed in vivo. [ABSTRACT FROM AUTHOR]

Motivation: Many important problems in cell biology require dense non-linear interactions between functional modules to be considered. The importance of computer simulation in understanding cellular processes is now widely accepted, and a variety of simulation algorithms useful for studying certain subsystems have been designed. Expansion of hematopoietic stem and progenitor cells (HSC/HPC) in ex vivo culture with cytokines and small molecules is a method to increase the restricted numbers of stem cells found in umbilical cord blood (CB), while also enhancing the content of early engrafting neutrophil and platelet precursors. The efficacy of the expanded product depends on the composition of the cocktail of cytokines and small molecules used for culture. Testing the influence of a cytokine or small molecule on the expansion of HSC/HPC is a laborious and expensive process. We therefore developed a computational model based on cellular signaling interactions that predict the influence of a cytokine on the survival, duplication and differentiation of the CD133+ HSC/HPC subset from human umbilical CB. Results: We have used results from in vitro expansion cultures with different combinations of one or more cytokines to develop an ordinary differential equation model that includes the effect of cytokines on survival, duplication and differentiation of the CD133+ HSC/HPC. Comparing the results of in vitro and in silico experiments, we show that the model can predict the effect of a cytokine on the fold expansion and differentiation of CB CD133+ HSC/HPC after 8-day culture on a 3D scaffold. [ABSTRACT FROM AUTHOR]

Mathematical and computational models are increasingly used to help interpret biomedical data produced by high-throughput genomics and proteomics projects. The application of advanced computer models enabling the simulation of complex biological processes generates hypotheses and suggests experiments. Appropriately interfaced with biomedical databases, models are necessary for rapid access to, and sharing of knowledge through data mining and knowledge discovery approaches. [ABSTRACT FROM PUBLISHER]

Vaccine research is a combinatorial science requiring computational analysis of vaccine components, formulations and optimization. We have developed a framework that combines computational tools for the study of immune function and vaccine development. This framework, named ImmunoGrid combines conceptual models of the immune system, models of antigen processing and presentation, system-level models of the immune system, Grid computing, and database technology to facilitate discovery, formulation and optimization of vaccines. ImmunoGrid modules share common con- ceptual models and ontologies. The lmmunoGrid portal offers access to educational simulators where previously defined cases can be displayed, and to research simulators that allow the development of new, or tuning of existing, computational models. The portal is accessible at . [ABSTRACT FROM AUTHOR]