A Stochastic Model for CD4+ T Cell Proliferation and Dissemination Network in Primary Immune Response.

The study of the initial phase of the adaptive immune response after first antigen encounter provides essential information on the magnitude and quality of the immune response. This phase is characterized by proliferation and dissemination of T cells in the lymphoid organs. Modeling and identifying the key features of this phenomenon may provide a useful tool for the analysis and prediction of the effects of immunization. This knowledge can be effectively exploited in vaccinology, where it is of interest to evaluate and compare the responses to different vaccine formulations. The objective of this paper is to construct a stochastic model based on branching process theory, for the dissemination network of antigen-specific CD4+ T cells. The devised model is validated on in vivo animal experimental data. The model presented has been applied to the vaccine immunization context making references to simple proliferation laws that take into account division, death and quiescence, but it can also be applied to any context where it is of interest to study the dynamic evolution of a population.

A remote lab for experiments with a team of mobile robots.

In this paper, a remote lab for experimenting with a team of mobile robots is presented. Robots are built with the LEGO Mindstorms technology and user-defined control laws can be directly coded in the Matlab programming language and validated on the real system. The lab is versatile enough to be used for both teaching and research purposes. Students can easily go through a number of predefined mobile robotics experiences without having to worry about robot hardware or low-level programming languages. More advanced experiments can also be carried out by uploading custom controllers. The capability to have full control of the vehicles, together with the possibility to define arbitrarily complex environments through the definition of virtual obstacles, makes the proposed facility well suited to quickly test and compare different control laws in a real-world scenario. Moreover, the user can simulate the presence of different types of exteroceptive sensors on board of the robots or a specific communication architecture among the agents, so that decentralized control strategies and motion coordination algorithms can be easily implemented and tested. A number of possible applications and real experiments are presented in order to illustrate the main features of the proposed mobile robotics remote lab.

Vaginal immunization to elicit primary T-cell activation and dissemination.

Primary T-cell activation at mucosal sites is of utmost importance for the development of vaccination strategies. T-cell priming after vaginal immunization, with ovalbumin and CpG oligodeoxynucleotide adjuvant as model vaccine formulation, was studied in vivo in hormone-synchronized mice and compared to the one induced by the nasal route. Twenty-four hours after both vaginal or nasal immunization, antigen-loaded dendritic cells were detected within the respective draining lymph nodes. Vaginal immunization elicited a strong recruitment of antigen-specific CD4(+) T cells into draining lymph nodes that was more rapid than the one observed following nasal immunization. T-cell clonal expansion was first detected in iliac lymph nodes, draining the genital tract, and proliferated T cells disseminated towards distal lymph nodes and spleen similarly to what observed following nasal immunization. T cells were indeed activated by the antigen encounter and acquired homing molecules essential to disseminate towards distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and CD62L marker expression. A multi-type Galton Watson branching process, previously used for in vitro analysis of T-cell proliferation, was applied to model in vivo CFSE proliferation data in draining lymph nodes 57 hours following immunization, in order to calculate the probabilistic decision of a cell to enter in division, rest in quiescence or migrate/die. The modelling analysis indicated that the probability of a cell to proliferate was higher following vaginal than nasal immunization. All together these data show that vaginal immunization, despite the absence of an organized mucosal associated inductive site in the genital tract, is very efficient in priming antigen-specific CD4(+) T cells and inducing their dissemination from draining lymph nodes towards distal lymphoid organs.

A non-linear deterministic model for regulation of diauxic lag on cellobiose by the pneumococcal multidomain transcriptional regulator CelR.

When grown on glucose and beta-glucosides, S. pneumoniae shows sequential use of sugars resulting in diauxic growth with variable time extent of the lag phase separating the biphasic growth curve. The pneumococcal beta-glucoside uptake locus containing the PTS transporter spr0276-82, is regulated by a multi-domain transcriptional regulator CelR. In this work, we address the contribution of phosphorylation of the phosphorylable cysteine in the EIIB domain of CelR to diauxic lag. Utilising site-directed mutagenesis of the phosphorylable amino acids in the EIIB and EIIA domains of CelR, we show that the EIIB domain activation is linked to the duration of the lag phase. Analysis of mutants for other PTS systems indicates that a second beta-glucoside PTS (spr0505), not able to support growth on cellobiose, is responsible for the lag during diauxic growth. A mathematical model of the process is devised together with a nonlinear identification procedure which provides model parameter estimates characterizing the single phases of bacterial growth. Parameter identification performed on data recorded in appropriate experiments on mutants allows for establishing a relationship between a specific model parameter, the EIIB domain and the time extent of the diauxic lag. The experimental results and the related insights provided by the mathematical model provide evidence that the conflicting activation of the CelR regulator is at the origin of the lag phase during sequential growth on glucose and cellobiose. This data is the first description of diauxic lag regulation involving two PTS and a multidomain regulator and could serve as a promising approach for studying the S. pneumoniae growth process on complex carbon sources as possibly encountered in the human host.

Identifying the dynamics of complex spatio-temporal systems by spatial recurrence properties.

Complex spatio-temporal systems may exhibit irregular behaviors when driven far from equilibrium. Reaction-diffusion systems often lead to the formation of patterns and spatio-temporal chaos. When a limited number of observations is available, the reconstruction and identification of complex dynamical regimes become challenging problems. A method based on spatial recurrence properties is proposed to deal with this problem: generalized recurrence plots and generalized recurrence quantification analysis are exploited to show that detection of structural changes in spatially distributed systems can be performed by setting up appropriate diagrams accounting for different spatial recurrences. The method has been tested on two prototypical systems forming complex patterns: the complex Ginzburg-Landau equation and the Schnakenberg system. This work allowed us to identify changes in the stability of spiral wave solutions in the former system and to analyze the Turing bifurcations in the latter.

Periodic solutions in modelling lagoon ecological interactions.

In this paper we present and analyze a nutrient-oxygen-phytoplankton-zooplankton mathematical model simulating lagoon ecological interactions. We obtain sufficient conditions, based on principal eigenvalue criteria -- for the existence of periodic solutions. A decoupled model which arises in the high nutrient regime is then considered in further detail for gathering some explicit conditions on parameters and averages of exogenous inputs needed for coexistence. An application to Italian coastal lagoons is finally obtained by parameter estimation and comparison with real data. A biological interpretation of the mathematical results is also presented.