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Santo Motta

Bio: Santo Motta is an academic researcher from University of Catania. The author has contributed to research in topics: Cancer vaccine & Vaccination. The author has an hindex of 28, co-authored 85 publications receiving 1809 citations. Previous affiliations of Santo Motta include Mathematica Policy Research & National Research Council.


Papers
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Journal ArticleDOI
TL;DR: Mathematical and computational models are increasingly used to help interpret biomedical data produced by high-throughput genomics and proteomics projects and are necessary for rapid access to, and sharing of knowledge through data mining and knowledge discovery approaches.
Abstract: 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.

127 citations

Journal ArticleDOI
TL;DR: An in silico model that simulates the immune system responses to tumor cells in naive and vaccinated mice shows that the humoral response is fundamental in controlling the tumor growth and therefore suggests the selection and timing of experiments for measuring the activity of T cells.
Abstract: We present an in silico model that simulates the immune system responses to tumor cells in naive and vaccinated mice. We have demonstrated the ability of this model to accurately reproduce the experimental results. Motivation:In vivo experiments on HER-2/neu mice have shown the effectiveness of Triplex vaccine in the protection of mice from mammary carcinoma. Full protection was conferred using chronic (prophylactic) vaccination protocol while therapeutic vaccination was less efficient. Our in silico model was able to closely reproduce the effects of various vaccination protocols. This model is the first step towards the development of in silico experiments searching for optimal vaccination protocols. Results:In silico experiments carried out on two large statistical samples of virtual mice showed very good agreements with in vivo experiments for all experimental vaccination protocols. They also show, as supported by in vivo experiments, that the humoral response is fundamental in controlling the tumor growth and therefore suggest the selection and timing of experiments for measuring the activity of T cells. Contact: francesco@dmi.unict.it Supplementary information: http://www.dmi.unict.it/CIG/suppdata_bioinf.html

114 citations

Journal ArticleDOI
TL;DR: An established mouse model of preventive vaccination using HER-2/neu transgenic mice is employed to validate in silico-designed protocols that reduce the number of vaccinations and optimize efficacy and shows that an integrated in vivo-in silico approach could improve both mathematical and biological models of cancer immunoprevention.
Abstract: Cancer vaccine feasibility would benefit from reducing the number and duration of vaccinations without diminishing efficacy. However, the duration of in vivo studies and the huge number of possible variations in vaccination protocols have discouraged their optimization. In this study, we employed an established mouse model of preventive vaccination using HER-2/neu transgenic mice (BALB-neuT) to validate in silico-designed protocols that reduce the number of vaccinations and optimize efficacy. With biological training, the in silico model captured the overall in vivo behavior and highlighted certain critical issues. First, although vaccinations could be reduced in number without sacrificing efficacy, the intensity of early vaccinations was a key determinant of long-term tumor prevention needed for predictive utility in the model. Second, after vaccinations ended, older mice exhibited more rapid tumor onset and sharper decline in antibody levels than young mice, emphasizing immune aging as a key variable in models of vaccine protocols for elderly individuals. Long-term studies confirmed predictions of in silico modeling in which an immune plateau phase, once reached, could be maintained with a reduced number of vaccinations. Furthermore, that rapid priming in young mice is required for long-term antitumor protection, and that the accuracy of mathematical modeling of early immune responses is critical. Finally, that the design and modeling of cancer vaccines and vaccination protocols must take into account the progressive aging of the immune system, by striving to boost immune responses in elderly hosts. Our results show that an integrated in vivo-in silico approach could improve both mathematical and biological models of cancer immunoprevention.

83 citations

Journal ArticleDOI
TL;DR: NetLogo applications to immunology is summarized and how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms is summarized.
Abstract: Several components that interact with each other to evolve a complex, and, in some cases, unexpected behavior, represents one of the main and fascinating features of the mammalian immune system. Agent-based modeling and cellular automata belong to a class of discrete mathematical approaches in which entities (agents) sense local information and undertake actions over time according to predefined rules. The strength of this approach is characterized by the appearance of a global behavior that emerges from interactions among agents. This behavior is unpredictable, as it does not follow linear rules. There are a lot of works that investigates the immune system with agent-based modeling and cellular automata. They have shown the ability to see clearly and intuitively into the nature of immunological processes. NetLogo is a multiagent programming language and modeling environment for simulating complex phenomena. It is designed for both research and education and is used across a wide range of disciplines and education levels. In this paper, we summarize NetLogo applications to immunology and, particularly, how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms.

78 citations

Journal ArticleDOI
TL;DR: A simulator (SimTriplex) is developed which describes the immune response activated by Triplex vaccine and suggests that maximal protection could still be obtained with a number of vaccinations ~40% less than with the Chronic protocol.
Abstract: Immunological prevention of cancer has been obtained in HER-2/neu transgenic mice using a vaccine that combines 3 different immune stimuli (Triplex vaccine) that is repeatedly administered for the entire lifespan of the host (Chronic protocol). Biological experiments leave open the question of whether the Chronic protocol is indeed the minimal vaccination schedule affording 100% protection, or whether shorter protocols could be applied that would result in the same efficacy. A biological solution would require an enormous number of experiments, each lasting at least one year. Therefore we approached this problem by developing a simulator (SimTriplex) which describes the immune response activated by Triplex vaccine. This simulator, tested against in vivo experiments on HER-2/neu mice, reproduces all the vaccination protocols used in the in vivo experiments. The simulator should describe any vaccination protocol within the tested range. A possible solution to the former open question using a minimal search strategy based on a genetic algorithm is presented. This is the first step toward a more general approach of biological or clinical constraints for the search of an effective vaccination schedule. The results suggest that the Chronic protocol included a good number of redundant vaccine administrations, and that maximal protection could still be obtained with a number of vaccinations ~40% less than with the Chronic protocol. This approach may have important connotations with regard to translation of cancer immunopreventive approaches to human situations, in which it is desirable to minimize the number of vaccinations. We are currently setting up experiments in mice to test whether the actual effectiveness of the vaccination protocol agrees with the genetic algorithm.

77 citations


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Book
01 Jan 1993
TL;DR: In this paper, the authors propose a theory which goes beyond the classical formulation of thermodynamics by enlarging the space of basic independent variables, through the introduction of non-equilibrium variables, such as the dissipative fluxes appearing in the balance equations.
Abstract: Our aim is to propose a theory which goes beyond the classical formulation of thermodynamics. This is achieved by enlarging the space of basic independent variables, through the introduction of non-equilibrium variables, such as the dissipative fluxes appearing in the balance equations. The next step is to find evolution equations for the dissipative fluxes. Whereas the evolution equations for the classical variables are given by the usual balance laws, no general criteria exist concerning the evolution equations of the dissipative fluxes, with the exception of the restrictions imposed on them by the second law of thermodynamics.

1,739 citations

01 Dec 1982
TL;DR: In this paper, the authors study the solutions of the gravitational field equations which describe the contraction of a heavy star, and give general and qualitative arguments on the behavior of the metrical tensor as the contraction progresses.
Abstract: When all thermonuclear sources of energy are exhausted a sufficiently heavy star will collapse. Unless fission due to rotation, the radiation of mass, or the blowing off of mass by radiation, reduce the star's mass to the order of that of the sun, this contraction will continue indefinitely. In the present paper we study the solutions of the gravitational field equations which describe this process. In I, general and qualitative arguments are given on the behavior of the metrical tensor as the contraction progresses: the radius of the star approaches asymptotically its gravitational radius; light from the surface of the star is progressively reddened, and can escape over a progressively narrower range of angles. In II, an analytic solution of the field equations confirming these general arguments is obtained for the case that the pressure within the star can be neglected. The total time of collapse for an observer comoving with the stellar matter is finite, and for this idealized case and typical stellar masses, of the order of a day; an external observer sees the star asymptotically shrinking to its gravitational radius.

1,052 citations

Journal ArticleDOI
TL;DR: The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance.
Abstract: Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.

563 citations

Journal ArticleDOI
TL;DR: In this paper, the creation of gravitons in the inflationary universe and their effects on the 3K photon background were considered, and it was shown that the creation is compatible with existing experimental data on the large scale anisotropy of relic photons only if the energy density of the symmetric vacuum is much less than the Planck energy density, ϵV < 3 × 10−8 Mpl4.

519 citations